Milestones in European Thyroidology (MET)

Michel De Visscher (1915-1981)

Michel De Visscher was born in Oxford (UK) in 1915. His parents had fled Belgium because of the German invasion in World War I. His father Fernand was a jurist who was teaching Roman Rights at the University of Ghent and at the University of Louvain in Belgium. His uncle Charles De Visscher was Professor of International Rights, also in Louvain and later, became judge at the Court of International Justice in The Hague (The Netherlands). Michel grew up in an academic and very educated family, very open-minded to all the cultural and social problems of his epoch.

After excellent secondary studies, Michel De Visscher started his medical studies at the University of Louvain in 1932 and graduated as M.D. in 1939. Already as an undergratuate student, he was fascinated by the importance of experimental medicine in the understanding of diseases and their clinical manifestations. He worked as a "student researcher" in the laboratory of Physiology (Prof. J.-P. Bouckaert and Prof. J. Colle ) and became involved in the developing field of electrophysiology. In 1940, he presented a memoir entitled " Study on experimental auricular fibrillation".

During World War II, De Visscher kept working in Bouckaert's laboratory while being involved in the Belgian Resistance, an underground movement fighting the German occupying forces. In 1946, he presented his PhD thesis entitled "The hormonal regulation of metabolism and vitamin A". This work clearly indicated the new orientation and interest of De Visscher in thyroid pathophysiology. His studies were experimental and clinical, and particularly related to the modulating action of thyroid hormones and vitamin A on the action of epinephrine on the nervous system in hypo- or hyperthyroid states. He observed that the administration of vitamin A prevented to some extent the rise of the basal metabolic rate after thyroxine administration in rabbits or in hyperthyroid patients. While going on with his laboratory work, De Visscher performed his training in internal medicine. In 1948, he was appointed as Chargé de cours to the Louvain University Medical School and as Chef de clinique in the Department of Internal Medicine of the University hospital St Pierre in Louvain. He became full Professor in 1952 and held the chair of Pathologie générale (biochemical and pathological physiology ).

During the 1950s, Michel De Visscher made several scientific stays in Europe and went to the United States as C.R.B. advanced Fellow. He mainly stayed in 2 internationally well-known thyroid laboratories at the time, one in Yale with W. Salter and the second in San Francisco with I.L. Chaikoff. While in Europe, the only available approach for evaluating the level of thyroid activity still remained the measurement of the basal metabolic rate, the North-American research centers had kept some activities during World War II and particularly, in the development of methodologies for measuring protein-bound iodine (PBI), allowing to evaluate the level of total thyroxine in the blood. Since 1938 also in the US, radioiactve iodine had been available to investigators and became routinely used for research, clinical diagnosis and therapy from 1945 on.

In Europe, radioiodine 131I only became available 10 years later, around 1955. Right after the war, all what was related to radioactivity (and thus the atomic bomb) remained classified as a defense secret and was not available for civil use.

In 1941, Salter and coworkers had demonstrated the relationship between the blood protein-bound iodine (PBI) and the thyroid function. However, the methodology of the PBI determination remained very delicate, highly sensitive to any iodine contaminations and time-consuming. In 1950, Christian Beckers joined De Visscher's recently created Laboratoire de Pathologie Générale associated to his chair, as an undergraduate student and started participating in the life of the recently born laboratory by working on the setup of the methodology for measuring PBI. In these days, one person was able to make 6-8 PBI determinations a day using the manual dry-ashing method of Barker. Only several years later would the automatization of the PBI become available with the Technicon auto-analyzer.

New laboratory spaces were soon made available to the Laboratoire de Pathologie Générale at the university hospital. Michel De Visscher had well understood the importance of the use of radioactive tracers for physological and biochemical investigations. At that time, radioiodine 131I was almost the only tracer available (125I came much later).

Michel De Visscher developed with J. Lammerant the appropriate technology to measure the cardiac output using radioiodinated serum albumin. Their studies were particulaly focused on the pulmonary circulation in various clinical conditions. After Christian Beckers' return from his stay with John Stanbury at the MGH in Boston, radioiodine (131I) studies became an essential tool to quantify the thyroid function and a more biochemical approach of thyroid metabolism took place.

De Visscher's laboratory team rapidly expanded and attracted other people. The group included B. de Crombrugghe, Ph. De Naeyer, J.-P.Herveg, P. Malvaux, L. Piret, G. Ponchon, M.-F. Vandenbroucke and H.-G. Van den Schrieck. They all developed personal and original researches in thyroid biochemistry, in the transport , the peripheral metabolism and the cellular receptors of thyroid hormones. Michel De Visscher was a wonderful boss, always paying attention to everyone, providing his coworkers with the best research facilities and giving his young people the best chances to develop their projects, to complete their clinical or laboratory experience by staying abroad in places of excellent academic prestige, particularly in the U.S. and upon their return at home, facilitating the integration of their expertise in the academic organization of the Louvain Medical School.

In 1957 and 1958, Michel De Visscher personally performed epidemiological studies in the former Belgian Congo (actually the Democratic Republic of Congo), more precisely in the Uele region in the Northern part of Congo (near Sudan) which was a region of high prevalence of endemic goiter and cretinism. Measurements of the iodine content of the drinking water and of the salt used for cooking demonstrated very low levels of iodine. In the euthyroid goitrous adults, the PBI was at the lower limit of normal while in cretins, the PBI clearly indicated a severe degree of hypothyrodism. Upon his return in Belgium and impressed by his experience in Congo, De Visscher made the project of going back to the Ueles with modern tools of investigation, particularly radioiodine. Having examined different possibilities of organization, he managed with Paul Bastenie, Head of the Department of Internal Medicine at the Université libre de Bruxelles (ULB), a joint research project, assisted by André Ermans and Christian Beckers. The first expedition happened in 1959 and the second one in 1960. Jacques Dumont joined the second field expedition.

During these 2 expeditions, detailed investigations on iodine kinetics, intrathyroid metabolism and cretinism were performed. The pioneer work of J.B.Stanbury et al. was definitely extended by adding original data on iodine turnover in endemic goiter, this including kinetic iodine studies ( 131I - 127I ) and the analysis of the iodoaminoacids content of thyroglobulin from goiters surgically removed in the local hospital. It was taking 24 hrs to transport the frozen blood and thyroid specimens from the bush to Brussels airport. Another contribution from these studies in the Ueles was a more detailed investigation of the cases of myxedematous cretinism previously observed by De Visscher in 1957. This clinical entity was partly different from the neurologic cretinism generally observed in other iodine deficient regions. Later on, cases of myxedematous cretinism were also reported from China and Indonesia.

While keeping interest for the pathophysiology of endemic goiter, particularly in the Chilean Andes and in Ecuador with C. Beckers, Michel De Visscher stimulated studies on different aspects of thyroid metabolism, particularly the circulating thyroxine-binding proteins, the physico-chemical properties and the synthesis of thyroglobulin, the iodine metabolism in sporadic nontoxic goiter. To support some of these investigations radioimmunoassays for TSH and T3 were developed at a time when commercial kits were not yet available.

In the meantime, Michel De Visscher continued with his activities and responsibilities in the Department of Internal Medicine and his teaching at the medical school. Within the Laboratoire de Pathologie Générale, two main sectors of activities were clearly developing, one in thyroid basic research and another related to the use of radiosotopes in medicine for clinical investigations, diagnosis and therapy, particularly in the field of thyroid. While De Visscher continued to head up the Laboratoire de Pathologie Générale, Christian Beckers became in charge of the newly-created Department of Nuclear Medicine in 1965.

Around the 1960s and for different social and political reasons, it was decided to move the medical school and the university hospital to the eastern part of Brussels and to build there a new campus. Michel De Visscher took a very active part in the planning, the negotiations and the transfer of the medical school and the university hospital to Brussels.

A new institute, the Institute of Cellular Pathology (ICP) was going to be created on the new medical campus in Brussels, under the leadership of Christian de Duve (Nobel Prize in Medicine 1974). De Visscher's laboratory joined the ICP in 1974. His lab took the name "Hormones and Metabolism", not just oriented to thyroid but also to insulin and steroids basic research.

During all these years, Michel De Visscher remained involved with the clinic and the patients. In 1973, he became head of the Division of Endocrinology and Nutrition in the new hospital, the Cliniques universitaires St Luc. In the meantine, the Thyroid Clinic he had started in 1957 never stopped developing.

Michel De Visscher hosted the 1st meeting of the European Thyroid Association in 1967, a meeting which is well kept in the memory of all the participants. Since the launch of the idea of an european thyroid society in 1965, he actively supported the foundation of the ETA of which he became the President in 1976-1978. In 1974, he made possible the creation of the Sir Charles Harington Prize lecture, later called the Harington-De Visscher prize. Michel was Membre titulaire of the Académie de Médecine in Belgium and belonged to many scientific societies. He was recognized as an active personality in the boards and committees of several research foundations.

Last but not least and in the spirit of his education, Michel De Visscher was an open-minded personality interested in all the human, humanistic and artistic aspects of life, aside medicine and science. He was very generous to everyone, especially to the young people. With his wife Jacqueline, they had 7 children. Their already large family became even larger by including all his laboratory families … The De Visscher's open-house was a permanent link between everyone. When Michel De Visscher passed away in 1981, Nino Salvatore then President of the ETA said at the 11th annual meeting of the ETA in Pisa "… Michel De Visscher was a gentleman we appreciated for his elegance and his never failing courtesy".

Pr Dr Christian Beckers, MD, PhD
University of Louvain Medical School (UCL, Belgium)