Faure_2008_Toxicon_52_400

http:\/\/www.sciencedirect.com/science/article/pii/S0041010108003899 Cassian Bon was born on March 31, 1944 in Vietnam. It was during a period of troubled times which he frequently evoked, and throughout his life he expressed an attachment and affection for the countries of South-east Asia and the Far East, particularly Vietnam and China. Soon returning to France, he pursued secondary studies at the Ecole Sainte Genevieve de Versailles, and in 1966 was admitted to the Ecole Normale Superieure, Paris, rue d'Ulm. He remained a faithful and active member in the associations d'anciens eleves of the Ecole Sainte Genevieve and ENS. In 1969 he began training in biochemistry with studies of aspartokinase I-homoserine dehydrogenase I from Escherichia coli, under the direction of Georges Cohen at the Pasteur Institute Paris. In 1972, a period of national service led him to work on studies of scorpion venom in the laboratory directed by France Tazieff at Pasteur. This experience was decisive: he would definitively work on the study of venoms, essentially snake venom and anti-venom serum throughout his dual scientific career in the CNRS and the Pasteur Institute. His thesis research was carried out under the direction of Jean-Pierre Changeux, and in 1979 he was awarded the Doctor of Science degree for studies on ceruleotoxin from Bungarus fasciatus and crotoxin from the South American rattlesnake Crotalus durissus terrificus. After obtaining his doctoral degree, Cassian became a research scientist in the CNRS and led a small group at Pasteur in the Cellular Pharmacology Unit directed by Boris Vargaftig. He was promoted director of research with the CNRS in 1987, director of the Unite des Venins at the Pasteur Institute in 1990, chef de laboratoire at Pasteur in 1991, and director of research at the French National Museum of Natural History in 2005. Cassian's scientific research was oriented successively in three directions. First, he continued studies of the mechanism of presynaptic neurotoxicity of snake venom phospholipase A2. He elucidated the functional role and synergistic action of the acidic subunit of crotoxin, a heterodimeric presynaptic alpha-neurotoxin that blocks transmission at the neuromuscular junction. Several years later he began studies on antivenom immunotherapy both in experimental and human cases, thus following a Pasteur tradition initiated by Albert Calmette in 1894. His work on the toxicological properties and kinetics of diffusion of snake venom in the organism was applied to measure the effectiveness on antivenom immunotherapy. He implemented a procedure using the ELISA method to determine quantitatively the levels of venom in the blood and urine of patients, and demonstrated the correlation of clinical symptoms with the quantity of circulating venom in the body. These results led to more effective protocols of serum administration and optimisation of treatment in clinical cases of envenomation. His scientific achievements were quickly recognized by the international scientific community, and as early as 1983 he began serving regularly as a consultant for the World Health Organization. Finally, he became increasingly interested in the anticoagulant properties of snake venom, and their potential role in the treatment of thrombotic accidents. His research group at the Pasteur Institute succeeded in isolating a number of important snake venom components including activators of prothrombin and factor X, convulxin (a potent platelet activator), bothrojaracin (a thrombin inhibitor), and TSV-PA (an activator of plasminogen). His group investigated the mechanism of the anticoagulant activity of human secretory group IIA blood platelet phospholipases A2 and extended these studies to homologous snake venom phospholipases. This important work demonstrated the molecular mechanism of phospholipid-independent anticoagulant activity of group IIA phospholipases A2 through inhibition of the prothrombinase complex by direct binding to human coagulation factor Xa. His dual career with the CNRS and the Pasteur Institute evolved in parallel with his scientific achievements. He was director of the Department of Physiopathology at the Pasteur Institute from 1994 to 1997 and became a director of research, first class, with the CNRS in 1997. He was a member of the Scientific Council of the Institute Pasteur Paris from 1995 to 1999 and of the Pasteur Institute Iran from 1998 to 2004, and was active both in French and international scientific societies including Societe francaise pour l'etude des Toxines, of which he was cofounder in 1992 and president from 2000 to 2008, Societe francaise de Biochimie et de Biologie moleculaire, Societe des Neurosciences, International Society of Toxinology, and International Society of Thrombosis and Haemostasis. Cassian's work on the treatment of envenomation is certainly among his most memorable scientific achievements, bringing him into close contact with problems of public health, particularly important in countries of the Far East. He became fully engaged in these efforts after observing the protective effect of monoclonal antibodies directed against a single subunit of crotoxin. His observations led to a new approach to immunotherapy in cases of ophidian envenomation involving primarily a single toxin. He extended these studies to scorpion neurotoxins and the toxicokinetics of venom diffusion, and the scientific publications resulting from his work remain an important reference in the field. He further approached the field of medicine by conducting in France a retrospective survey of ophidian envenomation, the results of which have been widely distributed in hospitals throughout the world. As a consequence of his important contributions to the field, Cassian was invited regularly as a consultant on ophidian envenomation and therapy in the Expert Committee on Biological Standardization of the World Health Organization. At the Pasteur Institute he was closely associated with the international Pasteur institutions of Tunisia, Algeria, Morocco, and Iran involving the production of antivenom serum. He remained a member until 2004 of the Scientific Council of the Pasteur Institute Iran. In France (Paris, Rennes, Marseille) he was actively involved in teaching tropical pathology and devoted many hours to courses on envenomation and therapy. His teaching activities extended beyond the field of tropical pathologies: he participated in the creation of the doctoral program of the Museum of Natural History (1995) and teaching in the doctoral and masters programs of the Museum. Cassian had the ability to communicate to his students a passion and enthusiasm for the field of toxinology. He directed fourteen thesis projects at the Pasteur Institute and in the Unite des Venins he hosted research workers and students from all over the world (China, Japan, USA, India, Brazil, Colombia, Mexico, Martinique, Vietnam, Iran, Poland, Germany, Slovenia, Algeria, Tunisia, Cameroun). The later years were marked by difficulties and illness which he faced with remarkable energy and determination. After the closing in 2004 of the Unite des Venins which he directed at the Pasteur Institute since 1990, Cassian joined the laboratory of Chimie des Substances Naturelles of the Museum of Natural History, where he found a welcome and familiar environment for teaching and research. His first priority was teaching. He was active in organizing scientific conferences and devoted particular efforts to the annual meeting of the Societe francaise pour l'etude des Toxines, of which he was president since 2000. He died on March 20, 2008 after a short hospitalization. He leaves among his many friends and colleagues the memory of a generous personality of considerable scientific stature, energy and tenacity.