Constantin Levaditi (1874-1953)
Constantin Levaditi graduated from the Faculty of Medicine in Bucharest (1897).
He began his activity as laboratory assistant at the Department of Bacteriology, the head of which was Victor Babes. In Paris he was laboratory assistant at the Department of Immunology. He continued his studies of immunity with Ehrlich in Germany. On his return to France, Levaditi was admittedÂ to the Â«Pasteur InstituteÂ» by Metchnicoff, who guided him in his experiments in the field of phagocytosis.
Levaditi had significant contributions in virology, syphiligraphyÂ and chemotherapy. In 1909 heÂ demonstrated, in cooperation with Karl Landsteiner, the presence of the poliovirus in other tissues than in the nervous one, namely in the nasopharyngeal secretions, in the salivary glands and in the intestinal lymph nodes.
In 1911, Levaditi isolated the poliovirus on a tissue explant, defined the histopathology of the experimental disease and demonstrated the ultrafiltrability of the poliovirus. Already in 1912 he tried to applyÂ the chemoprophylaxis of the disease by intranasal route, a problem of actuality for the rhinoviruses.
After 1920, Levaditi, assisted by 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.Â The investigations performed from rabies outlined an important chapter of the virological research on: the neurotropic ectodermoses. Levaditi introduced the term Â«neuroprobasiaÂ», which defines the progression of viruses along the nerve tracts.
Levaditi (in cooperation with P.Lepine) coordonated two of the first treatises of virology: Â«Les ultravirus des maladies humainesÂ» (Â«Ultraviruses of human diseasesÂ») (1936) and Â«Les ultravirus des maladies animalesÂ» (Â«Ultraviruses of animal diseasesÂ») (1943).
Levaditi had remarkable disciples in France (Pierre Lepine, M.Giroud), in England (Galloway), in Spain (Sanchez â€“Baiary), but especially in Romania: Stefan S.Nicolau, N.M.Constantinescu, N.Cajal, Pierrette Athanasiu, Ion Mesrobeanu, N. Stamatin, etc.
Stefan S. Nicolau (1896 - 1967)
Stefan S. Nicolau obtained in 1920 the M.D. (Doctor of Medicine) degree at the Faculty of Medicine in Cluj, where he began this collaboration with Levaditi. Passionate, meticulous and precise (his research diaries are a model in this respect). Nicolau succeeded until 1939 authored pioneering studies regarding viral diseases such as: herpes, rabies, poliomyelitis, poxovirus infections (especially vaccinia), aphthous fever, Borna disease fawlepithelioma, Aujeszkyâ€™s disease, Â«looping illnessÂ» and others. Among the worldwide acknowledged priorties we mention: the first detection of inclusions in the yellow fever â€“ a diagnostic criterion of this arbovirus infection; the introduction of the synchronophylaxis concept, a fact which promotes him as a, precursor of the interference phenomenon description; the discovery of the photodynamic action of stains (which is nowadays widely used in viral mutagenesis research on); the description of the septic neuritis and others.
In 1922, Levaditi and Nicolau published a series of articles in which new properties of the viral agents are demonstrated: ultrafiltrability (passage through the pores of a collodion membrane) and the cell-mediated character of the antiviral immunity. In a broad prospective view of the pathogenesis of viral infections, Levaditi and Nicolau underlined, beside the viral cytocidal effect, the participation of the immune response of the host in the triggering of the symptomatology.
Stefan S. Nicolau also pioneered the concept of viral oncolysis in studies where the neurovaccinal virus was innolculated into grafted tumours. -Levaditi C. and, Nicolau S., Virus et tumeurs. Ann Inst Pasteur 1923, 37, 1-3. cited in Sinkovics JC & Horwath J, Viruses and cancer. Medical Hypotheses 1995, 44, 359-368. "An innovative concept developed by Levaditi and Nicolau was viral oncolysis. Tumours are more susceptible to viruses than normal cells and tumours act as "a sponge attracting viral replication". This hypothesis was rediscovered by Sinkovics and Horwath in 1995 and is now in the centre of interest for many biotechnology companies who enlarge cancer virotherapy models".
With a remarkable intuition Nicolau promoted the concept of the oncogenic potential of the viral nucleic acids. He developed the infravirus concept â€“ the autonomized form of viral nucleic acids which, after its integration in the host cell genome, contributes to the viral transformation and the occurrence of various morbid states.
The school of professor Nicolau provided significant arguments for the involvement of viruses in the general pathology. Thus, morphological data supported the viral (inframicrobial) etiology of some cardiovascular diseases (arteritides, myocarditides) and the role of chlamydia, rickettsia and other viruses in the etiopathogenesis of some congenital/malformations and spontaneous abortions.
Stefan S. Nicolau isÂ he founder of the Institute of Virology of the Romanian Academy. The Â«Stefan S.NicolauÂ» Institute of Virology, which chronologically is one of the first institutions in this speciality in Euorpe, has celebrated in 1999 the 50th anniversary of its foundation. The Institute has ith origin in the nucleus of the Chair of Virology, which began its activity in 1942 in the framework of the Faculty of Medicine in Bucharest. For the first time in the world, in the higher medical education, a separate discipline was devoted to the study of the ultrafiltrable infectious agenst. Afterwards, a team of inframicrobiology of the Academy was created, wich developedÂ into the actual Institute of Virology. Many disciples of the school founded by prof. Nicolau distinguished themselves by significant contributions: Adelina Derevic (respiratory viral infections), Elisabeta Nastac (virus-cancer relationships), Elena Oprescu (respirtory viral infections), Radu Portocala (biochemistry of the viral nucleic acids), Dan Sarateanu (ornithoses), Constantin Surdan (Rickettsia), Nicolae Cajal his succesor at the Institute and Chair of virology direction.
Nicolae Cajal Â (1919 â€“ 2004)
He graduated from the Faculty of Medicine in Bucharest and worked, on the recommendation of professor Nicolau, at the Pasteur Institute in Paris, under the guidance of Levaditi. From 1967 to 1994 he was Director of the Stefan S. Nicolau Institute of Virology.
Disciple Â and collaborator of Professor Nicolau, N.Cajal published during his lifetime numerous reference studies regarding the persistent infections (herpes, papillomatosis, measles); the genetics of polioviruses and of other attenuated Â strains used in the prophylaxis of some viral diseases; the virus cancer relationships, as will as the relationships between the viral infections and the pathology of pregnancy and of the product of conception.
The scientific Â contribution of Professor Cajal is recorded in more than 400 papers published in Romania and abroad. Among the textbooks published we mention: Â«The laboratory diagnosis of human inframicrobiosesÂ» (1958), Â«PoliomyelitisÂ» (1960) Â«RabiesÂ» (1962), Â«Clinical laboratory methodsÂ» (1964), Â«Elements of general inframicrobiologyÂ» (1965), Â«Viral hepatitidesÂ» (1974), Â«Viral slow-course encephalitides and encephalopathiesÂ» (1974), Â«Measles, etiopathogenesis and prophylaxisÂ» (1978), Â«Non-poliomyelitic enteroviral infectionsÂ» (1983), Â«Pathogenesis of the chronic viral infectionsÂ» (1983). In 1990, under the editorship of Professor N.Cajal appeared the first volume of a remarkable treatise of Medical Virology.
In collaboration with Professor Stefan Nicolau, Professor N.Cajal sustained and developed the concept of plurietiology of viral hepatitis. On the basis of an extensive clinical Â and pathomorphological study, the authors demonstrated the existence of several other viruses, with the exception of the recognized A and B types. Later research on performed in various countries confirmed the conception and the priority of the Romanian authors.
In 1960, Professor Cajal initiated the antipoliomyelitic vaccination in Romania with the Sabin vaccine and followed-up the immunization level by antibody dosages. Objects of Â concern for the elaboration andÂ improvement of vaccines werease the anti-influenza and anti-measles vaccines, and the effect of their administrtion by intranasal or intraconjunctival route was followed-up.
Professor Cajal trained a true generation of researchers involved in applied medical virology, among whom we mention: Vincent Babes (viral hepatitis) Yolanda Copelovici (viruses â€“ pregnancy pathology relationships), Georgeta Danielescu (interferons), A.Mutiu (cell cultures), A.Petrescu (influenza); V.Jucu (viral persistence); C.Cernescu (his succesor at the Institute and chair of virology director).
Radu Portocala (1915 â€“ 1993)
Radu Portocala was Scientific Director of the Stefan S. Nicolau Institute of Virology from 1968 to 1973 and head of the Department of Biochemistry â€“ Biophysics. Dr Portocala was a founding member of the Institute with Stefan S. Nicolau. He spent the last period of his activity at the Â«Â PasteurÂ Â» Institute in Athens. Dr. Radu Portocala promoted molecular virology programs in the institute and authored the textbook Â«Â Les acides ribonucleiques cellulaires et virauxÂ Â» (The cellular and viral ribonucleic acids) (1966). Dr. Portocalaâ€™s team was at the forefront of viral nucleic acid research and authored important studies on interactions of the viral genome with physical and chemical agents.
Costin Eugen Cernescu
Professor Costin Eugen Cernescu ascended all the steps of the didactic career and of the medical specialization from assistant and resident to senior physician and professor. He began this activity at the Institute of Virology of the Romanian Academy in 1967 as assistant at the Department of Inframicrobiology and as researcher and to works here also now, in the function of honorary director of the Institute.
At the Institute, Dr. Cernescu worked in a close collaboration with Academician Nicolae Cajal and published numerous studies regarding the persistent neuroinfections, the genetics of attenuated viruses used in the prophylaxis of some viral diseases, the antiviral immunnity. He published also several monographs, among which we mention: Â«Viral vaccinesÂ» (1970), Â«Measles etiopathogenesis and prophylaxisÂ» (1978), Â«Vaccines and vaccinationsÂ» (1980), Â«Pathogenesis of the chronic viral infectionÂ» (1984).
His scientific research activity included also other fields: production and control of the live attenuated measles vaccine prepared on a new substrate human diploid cells; persistent viral neuroinfections â€“ subacute sclerosing panencephalitis and multiple sclerosis; molecular interferon induction mechanisms. In collaboration with numerous researchers from USA, from France and from other centres of Romania, Prof.Cernescu published significant studies regarding the emergence of the AIDS epidemic in the Constantza district; monitoring of its epidemiology by reevaluation of the case definition and of the disease staging; aspects of the AIDS encephalopaty in children; role of the macrophage in the pathogenesis of the HIV infection.
Prof. Cernescu was also interested in the study and the management of some viral epidemics which occurred during the last years in Romania, such as the study of the West-Nile meningoencephalitis, which acquired an epidemic form in 1996. Likewise, the study of the epidemiology of some parenterally transmitted viral diseases, such as the hepatitis B and C, and the study of sexually transmitted viral diseases and of eruptive viral diseases in children are fields of a permanent interest.
Prof. Cernescu is at present vice-president of the Balkan Society of Microbiology,Â member of the International Association of Physician in the AIDS care, member of the editorial board of the journals Â«Viral ImmunologyÂ» MA Liebert Inc.Pbl.), Â«Journal of Cell and Mol.Med.Â», Â«Proceedings of the Romanian AcademyÂ», series B, and Â«Studies and Research on of VirologyÂ».
In his capacity of evaluator he has also participated in the national programmes applied under the aegs of the Romanian Academy, of the Ministry of Education and Research, of the Fogarty International Center and of the European Community (FP 5 and 6). In 2001 he was electid corresponding member of the Romanian Academy. He is the author of 131 articles indexid in thosedline, of which we mention those published during the last years in the Â«LancetÂ», the Journal of Infectious diseases, Â«Viral ImmunologyÂ», Â«Clinical Laboratory DiagnosisÂ». He edited also a significant series of textbooks and monographs. We mention: Â«The textbook under the editorship of Acad. N.Cajal, Medical Publishing, House Bucharest, 1989; Â«Medical Virology, lecture notes, Medical Publishing House, 3 editions: 1998, 1999, 2000; Â«Practice of the Virological DiagnosisÂ», ConceptÂ Publishing House, 1999; Â«Nobel Prize for medicineÂ», Chimprest, Bucharest, 2001; Â«Antiviral DrugsÂ» (in collaboration with Simona Ruta). Professor Cernescu has trained and conducted a competitive team in the field ofÂ virological research and in the framework of the universityÂ education (Constanta Antipa, Carmen Diaconu, Gratiela Tardei, Violeta Chivu, Dorina Veliceasa, Mihaela Chivu, Coralia Bleotu, Irina Alexiu, Simona Ruta, Loredana Manolescu, Camelia Sultana).
Already from 1963, after his graduation from the Faculty of Medicine in Bucharest, he opted, during his preclinical training as an intern, for the field of virology, which he did never abandon, not even now. From 1966 onward, he undertook all steps of the academic career, obtaining the senior scientits (chief researcher) degree. During period 1963-1964 he worked in the "Virus-tumor relationship" team, the coordinator of which he became after 1987.
His scientific activity includes particularly interesting approaches to the viral study of some human neoplasia, of the bovine leucosis, of the genesis dynamics of antiviral antibodies in patients with neoplasia. Other projectsÂ had as object the use of the viral oncolysis in the human medicine, theÂ immunotherapy in cancer, correlation between the hepatitis B virus and the hepatocellular carcinoma, involvement of the human papillomaviruses in the malignant pathology. He obtained in these fields, a series of significant results, which were published in Romania and abroad.
Dr. Mihai Stoian benefittedÂ by courses and training stages abroad, at outstanding speciality institutions: in 1978 a course of immunovirology in cancer (Lyon), in 1993 a Tempus scholarship at the Pasteur Institute (Paris).
He published more than 140 scientific articles. In 1998, for a series of articles regarding the role of papillomaviruses in the malignant pathology he was distinguished with the â€œStefan S.Nicolauâ€ prize of the Romanian Academy.
For more than 25 years, Dr Stoian taught virology to medical students assistent professor at the virology chair of the â€œCarol Davilaâ€ University of Medicine and Pharmacy in Bucharest. He obtained successively the professional degrees of specialist physician and senior physician in the specialities microbiology, virology and parasitology. He is doctor of medical sciences and coordinator the training for of the M.D.degree.
Dr. Mihai Stoian was Principal Investigator of a number of research projects in the framework of the Romanian Academy, of the Ministry of Research and of the National Agency for Science and Technology.
In the framework ofÂ Â the Ministry of Research, he works as expert evaluator (VIASAN, BIOTECH, CNCSIS andÂ CORINTÂ PROGRAMMES).
Dr Mihai Stoian was very appreciated for his professional and managerial activity and therefore he was appointed scientific secretary in 1987, deputy director in 1999 and director of the â€œStefan S.Nicolauâ€ Institute of Virology in 2005.
In 2006 The Romanian Academy has appointed Prof. Stefan Constantinescu as IVN Honorary Director for EU Cooperation, a position similar to chair of international advisory board. Prof. Stefan Constantinescuâ€™s research unit at the Ludwig Institute for Cancer Research and the Christian de Duve Institute of Cellular Pathology in Brussels revolves around molecular cell biology, hematology/oncology, and virology.
The laboratory is involved in the study of the mechanisms of action of cytokines such as erythropoietin, thrombopoietin and G-CSF in blood cell formation and cancer, http://www.licr.ucl.ac.be/stg/stg.html,www.licr.org/12124501528/newslink/0509. In collaboration with the group of Dr. William Vainchenker at the Institut Gustave Roussy in Villejuif, the laboratory of Dr. Constantinescu contributed to the discovery of the JAK2 V617F mutation as a critical molecular determinant of human myeloproliferative diseases and more recently described novel mutations in the thrombopoietin receptor that might be essential for hematological malignancies.
Dr. Constantinescu has published significant papers in the field of cytokine receptor traffic, dimerization, structure and function, on the role of transmembrane sequences in protein oligomerization and has received his postdoctoral training with prof. Harvey Lodish at the Whitehead Institute for Biomedical Research at the Massachussets Institute of Technology, Cambridge, MA.
FORMER SENIOR SCIENTISTS
Liviu M. Popa (1930-1995)
Liviu M. Popa was senior scientist and head of department at the Â«Â Stefan S.NicolauÂ Â» Institute of Virology and professor of biochemistry and molecular biology at the Polytechnic Institute in Bucharest and at the Faculty of Medicine and Pharmacy in Cluj (afte 1990). His doctorate thesis opened new perspectives on the study of organic macromolecules by the partition of nucleic acid on chromatographic columns. The focus of his research programmes concerned the biochemistry of viral nucleic acid and proteins, their interactions with small molecules the characterization of the secondary structure of nucleoproteins by means of physico-chemical methods, the enzymatic activity of viral proteins.
The last years of his activity were marked by articles about human papillomaviruses involving an oncogenic pisk, by optimization of the diagnostic methods, and by attempts at esplaining the mechanism of the protein 7 of HPV 16 â€“ mediated carcinogenesis. Prof. Liviu M. Popa is credited with introducing molecular biology in Romania, and with teaching the first Molecular Biology course in Romania (with Dr Rodica Repanovici) at the Polytechnic Institute in Bucharest. Prof. Liviu Popa authored several Romanian textbooks of molecular biology.
Nicolae Draganescu (1922 â€“ 1994)
He received the M.D. (Doctor of Medicine) degree in 1968 and worked more than 40 years as researcher at the Institute of Virology, especially in the field of viral neuroinfections. He published more than 280 scientific articles and 5 textbooks, among which Â«Human viral encephalitidesÂ» (1962), Â«ArbovirusesÂ» (1970), Â«Transmissible spongiform encephalopathiesÂ» (1983). He was one of the first researchears who studied the transmission of prionic neuroinfections to animals and who defined the morphological picture of the slow-course encephalopathies in humans.
His research in the field of viral neuroinfections referred to various encephalitis forms detected on the territory of Romania, to the subacute sclerosing parencephalitis of the child and of the adult, to viral meningitides, to arbovirus infections and to the neurological complications of viral enteropathies. For more than 25 years, the incidence of infections wich arbovirus groups B, California, Kemerovo, etc. was followed-up on the whole national teritory and, for the first time in Romania, the isolation of the tick borne emcephalitis and of the West Nile encephalitis was successfully performed.
For his work on viral neuroinfections, Dr. N. Draganescu was distinguished with the Hadot Prize, conferred by the Academy of Medicine in Paris.