Constantin Levaditi

Constantin Levaditi was born in Galați. His father, Spyridon Livaditis, of Greek descent (from Macedonia) was 30 years old and working as a customs officer. His mother, Ioana Ștefănescu, then aged 18 years, was the daughter of peasants from Focșani. The family name originates from the name of the town of Livadia, a town 150 kilometres (93 mi) north of Athens[2] (Livaditis means one who comes from Livadia).[3]^: 872 The researcher Pierre Lépine [fr] (1901–1987) reported that Spyridon Livaditis was a member of the Filiki Eteria (Society of Friends), established to organize the Greek Revolution of 1821 against the Ottoman Empire under the leadership of Prince Alexander Ypsilantis.[1]^: 1 However, after he had graduated from the Medical School, Constantin altered his surname from Livaditis to Levaditi, which is the alternative spelling of the town (Livadia is also Levadia).[2]

Constantin Levaditi had a difficult childhood due to financial problems in the family. In September 1880, he went to the "Cuza Vodă" primary school in Galați, and at the same time started work at the store of his uncle Ștefan Ștefănescu. After the untimely death of his parents in 1883, Constantin’s aunt Efrosini, a member of his father’s family, took custody and he continued his basic education in Bucharest.[1]^: 1 He studied at Matei Basarab High School in Bucharest and at the Carol Davila University of Medicine and Pharmacy (1892-1896), where he studied under Victor Babeș. He had the opportunity to become familiar with a medical environment, as his aunt was a laundry worker at the "Brâncovenesc" Hospital in Bucharest. Thus, it was in a medical atmosphere that the future scientist grew up, a good student, gifted in mathematics, a lover of music and the theatre. His medical studies completed, Levaditi, an intern at the hospital, left it to his colleagues to make the ward rounds and spent his entire days in the laboratory. This is how he was noticed by Victor Babeș, of whom, in 1897, he became the assistant at the Bacteriological Institute. But he decided to leave for France: in 1898, he landed in Paris. After a passage in the laboratory of the academician Charles Bouchard, at the Hôtel-Dieu, he was, in 1899, assistant to Albert Charrin at the Collège de France.[4]^: 535

Levaditi continued his postgraduate studies in 1900 and 1901 in Frankfurt with Paul Ehrlich who was considered the father of modern chemotherapy. In the spring of 1901 Levaditi, following the advice of the physician John Kantakouzinos, had the great opportunity to work in the Élie Metchnikoff Laboratory at the Pasteur Institute. In 1902, he completed his doctoral thesis entitled Contribution a l’étude des Mastzellen et de la Mastzellen-Leycocytose (Contribution to the study of the mast cells and the mast cells-leucocytes), which was considered a pioneering contribution to haematology. Two years later, in 1904, Emile Roux recognized Levaditi’s abilities and enthusiasm and appointed him director of an independent laboratory at the Pasteur Institute.[1]^: 2

He will remain at the Pasteur Institute until retirement age. His choice is made: if he will remain sentimentally attached to his native Romania, it is France that has become his homeland because he has found there not only the means to work, but the intellectual atmosphere and the spiritual climate where he will be able to realize.[4]^: 536 He will return to Romania for a short trip in 1903, when he married Helen, the younger daughter of Dr. Constantin Istrati, and in 1920, as a guest lecturer at the University of Cluj.[1]^: 2

His enterprising research in immunology led to nomination as Professor in 1924. The American Professor Simon Flexner proposed him as director of the Rockefeller Institute for Medical Research in New York, but Levaditi refused politely. Meanwhile, Levaditi taught at many Universities all over the world including London, Madrid, Barcelona, New York and Philadelphia.[1]^: 2

The work of C. Levaditi is immense: it extends over more than half a century and it touches on apparently separate domains, but in reality they are united by the logical chain of thought and the development of research. His doctoral dissertation in medicine (1902) made Levaditi a cytologist and an immunologist. From this double training, C. Levaditi will always keep the imprint. Pathological histology will hold a considerable place in all his experimental work, itself oriented towards the solution of immunological problems raised by the various diseases he will study.[4]^: 536

Constantin Levaditi dedicated an important part of his research to the study of syphilis, a scourge of the 20th century. From 1907, when he began to investigate venereal disease systematically, he emphasized the importance of studying this wide-spread problem. Levaditi studied the invasive capability of Treponema pallidum into the target-organs and at the same time described the technique of staining this bacterium (the Levaditi–Manouelian method). He and Auguste-Charles Marie traced T. pallidum in the brainstem of patients suffering from neurosyphilis, a discovery that confirmed the infiltrating capacity of the organism and opened up new horizons for experimental study in animals. The two pioneer researchers also made the very significant observation that not only the antigens of T. pallidum, but also extracts of normal tissues from patients who had been infected by syphilis, gave a positive complement fixation reaction. This observation, in combination with the perfection of the serum detection method (the Wasserman Test), contributed to the discovery of autoantibodies and the phenomenon of autoimmunity.[1]^: 3

In his studies of syphilis, Levaditi introduced new techniques in serology, and recommended bismuth in its treatment. Entering World War I as a volunteer, he attained the rank of captain and was detached to serve with the ambulances of la Panne. In this capacity he worked on developing an antitetanus vaccine and studied streptococcus in wounds.[5]

Parallel to these works which would have sufficed to fill and illustrate a lifetime, and which after his retirement from the Institut Pasteur in 1940, he continued at the Alfred-Fournier Institute, from which he had, when it was created in 1932, received the scientific direction, C. Levaditi carried out with prodigious activity the research on viruses which made him the founder and leader of the French school in the field of ultraviruses.[4]^: 538 Levaditi was almost the first and, for a long time, the only person in France to study viruses systematically.[1]^: 4 C. Levaditi's works on viruses are numerous and each of them has had an epoch-making history.[4]^: 539

Nevertheless, Levaditi’s most significant contributions to mankind are his experiments in poliomyelitis and his catalytic assistance to the clarification of epidemiological factors causing this lethal disease. He cooperated with the Austrian Karl Landsteiner who was awarded the Nobel Prize in 1930 and who was considered a very important modern immunologist, known for the discovery of the ABO and Rhesus blood group system. Their main areas of cooperation were in the study of scarlet fever and especially of poliomyelitis.[6]^: 365

With Karl Landsteiner, he discovered in 1909 the presence of the poliovirus in tissues other than nervous. He expanded on these studies during a poliomyelitis outbreak in Sweden (in 1913),[5] working with Scandinavian researchers (among them Karl Oskar Medin); he was able to isolate the poliovirus on tissue explant and made precious observations on its characteristics. Together with Carl Kling, he authored the first monograph dedicated to the disease, La Poliomyélite aiguë épidémique (1913). His work was the basis for the development of the polio vaccine by Jonas Salk and Albert Sabin.

Apart from these major subjects, Levaditi touched on all branches of microbiology: tuberculosis, protozooses, immunology, each time with success, always with virtuosity, often as an innovator as in the study of toxoplasmosis or during the discovery of Streptobacillus moniliformis, agent of murine polyarthritis and epidemic erythema multiforme in humans.[4]^: 539 Levaditi’s scientific work has been characterized as ‘bridging the gap between nineteenth century pathology and twentieth century immunology’. Levaditi exercised an influence on both specialties. According to the historian John Paul, ‘there was scarcely a microbiological laboratory in Europe that did not boast of at least one worker who had been trained in Paris by Levaditi.’[7]^: 290

Levaditi spent almost his entire career at the Pasteur Institute. Though his was the only career beside Landsteiner’s to span the age of Pasteur and modern times, he was not well recognized in the history of poliovirus research. Moreover, unlike Landsteiner, Levaditi never relinquished his interest in poliovirus research after the discovery of the aetiologic agent of poliomyelitis by Landsteiner and Popper in 1908. Levaditi’s name has not been mentioned much in the history of medicine perhaps on account of his modesty. Those who met him described him as an enthusiastic, indefatigable researcher, fully aware of his saving work for mankind, and he always kept a low profile. In the words of his colleague John Paul, ‘it was a pity that he did not live two more years to witness the conquest of poliomyelitis achieved through the science of which he had so long been a champion, namely immunology’. Nevertheless ‘he lived to see his work with Kling and Lépine vindicated, and that was no small triumph.’[7]^: 290

In 1919, he returned to Romania. He stayed there for three years to teach at the University of Medicine and Pharmacy of Bucharest before holding, in 1921, at the request of the Romanian government, the chair of microbiology of the Faculty of Medicine of Babeș-Bolyai University in Cluj. After 1920, Levaditi, assisted by Ștefan S. Nicolau, elaborated at the Department of Bacteriology of the Faculty of Medicine in Cluj projects related to the study of other viruses: herpesviruses, vaccine virus and rabies virus group. The investigations performed from rabies outlined an important chapter of the virological research on: the neurotropic ectodermoses. Levaditi introduced the term “neuroprobasia”, which defines the progression of viruses along the nerve tracts.[8]

Constantin Levaditi was a member of the Académie Nationale de Médecine and an honorary member of the Romanian Academy. In 1928, he was awarded the Cameron Prize for Therapeutics of the University of Edinburgh. Throughout his career, Levaditi published more than 1,200 notes, articles, and monographs.[5]

• Levaditi, Constantin (1931). Travaux de médecine expérimentale. 1897-1931. Ectodermoses neurotropes. Neuroprotozooses. Syphilis. Chimiothérapie et chimioprévention. Phagocytose. Immunité. Erythème polymorphe. Rhumatisme infectieux. Ergostérol irradié [Experimental medicine work. 1897-1931. Neurotropic ectodermoses. Neuroprotozooses. Syphilis. Chemotherapy and chemoprevention. Phagocytosis. Immunity. Erythema multiforme. Infectious rheumatism. Irradiated ergosterol] (in French). Paris: Impr. A. Maretheux et L. Pactat. OCLC 459640006.
• Levaditi, Constantin (1952). Titres et travaux: Microbiologie, pathologie humaine & animale, chimiothérapie: 1897-1951 [Titles and works: Microbiology, human & animal pathology, chemotherapy: 1897-1951] (in French). Paris: Librairie Maloine. OCLC 1237121109.