In Search of the Ninth Discipline: The History of Pathophysiology, with an Emphasis on Pathophysiology in Varna, Bulgaria—Celebrating 100 Years of Pathophysiology in Bulgaria

Pathophysiology is a medical science whose subject is the change in regulatory mechanisms related to the onset, development, and outcome of diseases. The first lectures on pathophysiology were held in 1790 at the University of Erfurt, Germany, by Professor Augustus Hecker, who in 1791 also published the first work on the discipline – "Grundriss der Physiologia pathologica" in 770 pages. The teaching of pathophysiology as an independent discipline was introduced by academician Viktor Pashutin at the University of Kazan, Russia in 1874. Academician Pashutin called this new discipline “Pathological Physiology and Experimental Medicine.” Despite the persuasiveness of Pashutin that pathological anatomy and pathophysiology are inseparable parts of a whole, his students, academician Nikolay Anichkov and Prof. Semyon Khalatov, implemented the so-called “divorce” due to the different, though complementary, approaches and methodologies of the two ideological fields. By Royal Decree on November 29, 1917, in the Bulgarian State Gazette, amendments were published in the law on the national education, which introduced new university “disciplines and departments”. Under number nine in the law is the discipline of “Pathological Physiology and Experimental Medicine”. Due to various factors, the Pathological Physiology and Experimental Medicine department was the only one of the first 25 departments not to be established. The beginning of the training for pathophysiology in Bulgaria was laid by Prof. Vassil Mollov and Assoc. Prof. Minko Dobrev, however due to their untimely deaths, the course lasted only three years (1936–1939) and was not continued in the next academic year. At the beginning of the academic year 1946/47, two assistants in pathophysiology were enrolled in the Department of Pathological Anatomy at Sofia University. The following year a separate department was formed at the newly founded Plovdiv University and shortly after at Sofia University. For the 100 years since its legislative establishment, 82 years since its unofficial start and 71 years since its academic establishment pathophysiology in Bulgaria has distinguished itself by scientific, administrative and clinical contributions. In its 57 years in Varna, Bulgaria pathophysiology has widely carried out that tradition with immense contributions.


Introduction And Background
Pathophysiology is a medical science whose subject is the change in regulatory mechanisms related to the onset, development, and outcome of diseases. The first lectures on pathophysiology were held in 1790 at the University of Erfurt, Germany, by Professor Augustus Hecker (born 1.07.1763 -died 11.10.1811), who in 1791 also published the first work on the discipline -"Grundriss der Physiologia pathologica" in 770 pages [1]. In the 1830s, a distinguished school started forming, with members such as Johannes Müller (born 14.07.1801 -died 28.04.1985), Hermann von Helmholtz (born 31.08.1821 -died 8.09.1894), the father of cellular theory Rudolph Virchow (born 13.10. 1821 -died 5.09.1902) and the founder of experimental medicine Julius Friedrich Cohnheim (born 20.07.1839 -died 15.08.1884).
The teaching of pathophysiology as an independent discipline was introduced by Academician Viktor Pashutin (born 28.01.1845 -died 2.02.1901) at the University of Kazan, Russia in 1874. As head of the Department of Pathology, he decided to introduce a new discipline relying on the German pathophysiology society. Academician Pashutin called this new discipline "Pathological Physiology and Experimental Medicine".
Despite the persuasiveness of Academician Pashutin that pathological anatomy and pathophysiology are inseparable parts of a whole, his students Academician Nikolay Anichkov (born 1885-died 7.12.1964) and Professor Semyon Khalatov (born 26.02.1884-died 17.05.1951, authors of the first model of atherosclerosis in the world, implemented the socalled "divorce" due to the different, though complementary, approaches and methodologies of the two ideological fields.

Review
On the 10 th of April 1918, the dream of a number of Bulgarian activists, dating from before the liberation, was fulfilled for the establishment of a Medical Faculty on the territory of Bulgaria at Sofia University. Although the result of attempts to do so for nearly two decades, the structural and legislative bodies were not prepared for such a step, with a severe lack of staff, legal regulations and curriculum preparation [2].
By Royal Decree on November 29, 1917, in the State Gazette (year XXXIX, issue 226), amendments were published in the law on the national education, which for the first time introduces new university "disciplines and departments" (Figure 1) [2].
Under number nine in the law is the discipline of "Pathological Physiology and Experimental Medicine".
Due to various factors playing a role in driving the faculty, the staff set, and the necessary equipment, this was the only one of the first 25 departments not to be established, despite being included in the semester program of the third-year students. Even in the first year of the faculty, this presented as a serious problem, due to the transfer of two third-year students from foreign universities.
As a result of the many organizational problems, a pathophysiology course was not established. The basics of the discipline were reallocated between General Pathology, Propaedeutic of Internal Diseases and Propaedeutic of Surgical Diseases. The first few courses took the socalled Selected Chapters of Physiology in their last year of study, where the pathophysiological mechanisms of a number of disease processes were largely interpreted [2].
The beginning of the training in pathophysiology was laid by the Professor of Internal Medicine Vassil Mollov (born 22.11.1875 -died 22.12.1938) (1936)(1937)(1938)(1939) and was not continued in the next academic year [2].
The first officially recognized Department of Pathophysiology in Bulgaria was formed in 1947 at the newly founded Plovdiv University, under the supervision of Professor Luben Telcharov (born 17.11.1907 -died 1995), who specialized in Grenoble, Berlin, and Würzburg.
At the beginning of the academic year 1946/47, two assistants in pathophysiology were enrolled in the Department of Pathological Anatomy at Sofia University. The following year a separate department was formed under the supervision of the graduate and specialist in the Union of Soviet Socialist Republics (USSR) Associate Professor Stefan Ivanov Pisarev (born 28.02.1901died 12.03.1983) [2,3].
The newly founded Department of Pathophysiology found a difficult beginning of its existence. The methodology of teaching was rooted in Russian methods, while the majority of the medical community in Bulgaria was now already educated by the German model. At the same time, the newly formed Department faced well-established university disciplines with decades of experience, which have left a scientific footprint and have already produced their own professors.
Despite these problems, the department had a rapid pace of development. The experimental practices were adopted and approved by Soviet scholars, such as Professor Andrei Dimitrijevich Ado (born 12.01.1909 -died 29.10.1997). In 1958, a unique goal was set, which has not yet been achieved on a worldwide scale. The Department of Pathological Physiology required its transfer to a clinical setting on the territory of the Internal Diseases Clinic and a change of name to Department of Clinical Pathophysiology. The purpose of the Department's restructuring was to carry out complex clinical and experimental activities on its territory, together with clinicians and pharmacologists [2].
Little data remains for most of the first Bulgarian Pathophysiologists.
The first pathophysiologists at Plovdiv University N. Gaydadzhieva, M. Todorova, and Y. Pantev were the first assistants enrolled with the establishment of the Department of Pathophysiology at Plovdiv University. Sadly, today, no accessible biographical data has survived for them.  Professor Kemileva and Professor Popdimitrov left their mark not only on the teaching process, scientific and experimental activities in the early years of the newly formed University, but also gave significant administrative contributions, serving as Rector and Deputy Dean of the Faculty of Medicine, respectively [4].

The first pathophysiologists at Sofia University and the reformed HMI-Sofia
Under the supervision of Professor Kemileva, a number of changes were introduced in the university's research activities. The scientific periodical was renamed from Annual scientific papers -HMI Varna to Scripta Scientifica Medica, with the official language being changed from Bulgarian and Russian to English, 1965. The first scientific meeting of the newly formed institute was also held in 1965 [4].
The mandate of Professor Kemileva saw the establishment of new departments: Ear, Nose and Throat Diseases; Internal Diseases and Therapy; Ophthalmology; Social medicine; Forensic Medicine, as well as the establishment of a Central Diagnostic Laboratory of Virology and Microbiology [4].
Anelia Dyakova Uzunova (born 15.05.1933). Graduated from HMI Sofia in 1957. Ph.D. thesis "Experimental myocarditis and arthritis against a background of altered immunological reactivity", 1964 -the first successfully defended dissertation at HMI Varna. One of the few Bulgarian medics at that time to specialize in the USA -Washington, 1970-1972and 1974-1977 Later appointed as Head of the Department of Pathological Physiology at HMI Pleven, 1982-1999. Main scientific interests in the field of thymus involvement in immunological processes, pathogenesis of thrombosis and influence of eicosanoids in arterial thrombosis. Habilitated as a Professor in 1990 [4].
Kolyo Angelov Velikov (born 22.10.1927). Graduated from HMI Sofia in 1958. Ph.D. thesis "Experimental myocarditis and arthritis in adult rat dimeters", 1972. Main scientific interests in the field of rheumocardiology. After his retirement in 1988 until his death, he worked as a district and general physician in the village of Hursovo, Shumen. Habilitated as an Associate Professor in 1974 [4].
Ivan Kolev Kozarev (born 20.01.1937) (Figure 3). Graduated from HMI Sofia 1962. Ph.D. thesis "Influence of the Thymus on the immune-allergic reactivity of the organism", 1973. Main scientific interests in the field of immuno-allergic processes and thermal injuries. Founder and First Head of the Department of Pathophysiology at the affiliate of HMI Varna in Dobrich, 1978Dobrich, -1988. Subsequent Head of the Department of Pathophysiology at HMI, 1988-2000. His Ph.D. students include Ganka Bekyarova, MD and Radko Radev, MD, who served terms as Head of the department after his retirement. His guidance saw the habilitation as Associate Professor of his Ph.D. student Ganka Bekyarova. Habilitated as an Associate Professor in 1978 [4].