Pharmacology, From Rudolf Buchheim to Arnold Holste: the Founding of the Institute of Pharmacology at the Faculty of Medicine, University of Belgrade Establishment of the University Medical School in Belgrade - the first hundred years

The School of Medicine at the University of Belgrade celebrates its centennial anniversary. The Institute of Pharmacology and Toxicology, founded in 1924, played an important role in the School's life and development. It is not just about the scientific achievements, but above all, the exceptional personalities of our predecessors. If they spent their academic careers somewhere else, they would certainly have been among the most respected researchers in the world. The courage to stay in the turbulent Balkans and maintain successful communica-tion with colleagues from abroad deserves respect and admiration. One German and one Serb, professors Arnold Holste and Radivoje Pavlović, the latter with severely impaired sight, did an extraordinary job. They established a distinct pharmacological school, equipped research labs and provided their students with generous support despite the adverse circumstances (two world wars and persistent economic crisis, above all). Their younger associates, future professors Dimitrijević and Bogdanović, followed in the footsteps of their predeces-sors. Their example and sacrifice oblige us to keep pace with the extremely rapid development of pharmacology in the world.


Department of Pharmacology, Clinical
Pharmacology and Toxicology, University of Belgrade School of Medicine, Belgrade, Serbia. 2. University Medical Centre "Bežanijska kosa", Belgrade, Serbia.

Establishment of the University Medical School in Belgrade -the first hundred years
The end of the nineteenth and the beginning of the twentieth century in Serbia were marked by numerous debates and opposing views regarding the need to establish a medical faculty in Belgrade. On one side stood physicians Milan Jovanović Batut  and Đoka Nikolić, a member of the General Sanitary Council and on the other equally distinguished doctors -Vladan Đorđević and senior military officer Mihajlo Petrović, to mention only the most prominent among them. The former advocated the establishment of the faculty of medicine in Belgrade and supported the transformation of the Great School to the level of a university. They had a role model in the successful organisation of the University of Zagreb, where the initiative to establish a medical faculty has come a long way. However, the latter strongly opposed the establishment of the first medical faculty in Serbia, arguing that it was more reasonable to educate young doctors abroad and that the medical faculty was an expensive and complicated institution that required decades of investment in scientific staff and equipment. The need for medical staff was more than obvious -the situation in Serbian health care was challenging, but the conflict Pharmacology was first defined in 1791 by the German chemist and physicist Friedrich Albrecht Karl Gren (1760-1798), distinguishing between pharmacology as a science of drugs and materia medica as a list and description of drugs. 3 In the mid-1800s, pharmacology emerged as a separate scientific discipline, positioned between physiology and experimental pathology. 4  A brief history of pharmacology • Also, he explained the term "drug mechanism of action". • Last but not least, he introduced the experimental method in drug testing through animal experiments and bioassay.
Thus, it might be said that he was the real founder of experimental pharmacology. Before Buchheim, science of drugs was limited to collecting pharmacognostic information without in-depth analysis. The foundation of the Dorpat Institute of Pharmacology in the mid-nineteenth century dates back eight years before Virchow established cell theory and fourteen years before Paster's theory of germs. Buchheim also translated Jonathan Pereira's Materia Medica from English into German. Accordingly, Buchheim was not the first expert in therapeutic agent armamentarium. However, he was the first experimental

Institute of Pharmacology in Belgrade
pharmacologist in the modern sense of the term. Moreover, Buchheim improved Pereira's publication by adding a lot of new drugs and completed his own textbook of pharmacology (Lehrbuch der Arzneimittellehre) in 1848. It should be emphasised that the first clinical trials also gave impetus to the further development of pharmacology, such as the investigation of the effects of lemon in sailors with scurvy by Lind (published in 1753) or Wihering's research on the impact of foxglove in heart failure (1785).
Buchheim was active as a mentor -between 1847 and 1867, he supervised 90 papers, including 80 doctoral theses. His probably most successful student was Oswald Schmiedeberg (1838-1921), a Baltic German who established the first pharmacological journal, Archives of Experimental Pathology and Pharmacology (1873), the world-famous founder of the German pharmaceutical industry. 3 As a scientist, he discovered the importance of the chemical structure of drugs for their pharmacological action (structure-activity relationship  maceutical company in Switzerland. Holste subsequently moved to Strasbourg, Jena and finally Belgrade. 5,6 Upon his arrival in Belgrade, Professor Holste faced problems such as lack of Serbian language skills, the flawed premises of the Institute and lack of financial support. Such obstacles temporarily prevented him from continuing his scientific research. Three years later, when Pharmacology Institute moved to the new establishment, Holste continued his previous research on the interplay between calcium and digitalis, pharmacology of bile acids, etc. Holste wrote his papers in German, French, Italian and Serbian, which he soon mastered well. This native German, who did not know a single Serbian word after arriving in Belgrade, signed in Cyrillic after a few years and gave lectures fluently without an interpreter ( Figure 1).
Holste's research opus focused on the pharmacological effects of the active ingredients of herbal drugs (foxglove, peony, etc.), aspirin's vasodilatory properties and others. He was a distinguished scientist of his time, whose results were cited decades later. 7  Professor at the Medical Faculty in Belgrade. As a researcher, he was unique and versatile and as a lecturer, he was beloved and respected by students and doctors. This is not unusual, considering that Pavlović's life motto was: "I always want to be surrounded by satisfied and happy people." A particular achievement of Professor Radivoje Pavlović was the founding and editing of a prestigious international journal entitled: Medical Review (Medicinski pregled in Serbian) for 12 years (1926)(1927)(1928)(1929)(1930)(1931)(1932)(1933)(1934)(1935)(1936)(1937)(1938). Professor Pavlović's exceptional personality can also be portrayed by the fact that he was almost blind during the most productive years of his career, between 1926 and 1938, when he died at the age of 45. The loss of sight did not stop him from the numerous activities he performed with enormous enthusiasm and the generous support of his wife.
The title page of the paper from this journal is shown in Figure 2.  (Figure 3).
They studied abroad in top-level medical school and were loved and respected both by their peers and students. They established pharmacology departments at related higher education institutions, faculties of dentistry, veterinary medicine and pharmacy within the University of Belgrade. It is a great honour to work in the same institute as our dear professors and teachers and to continue their work. After the War, he successfully led our Institute for more than two decades, giving impetus to a highly successful development called the "golden age of the Institute." He was highly professional, authoritative, with pronounced pedagogical skills and a parental attitude towards the younger associates. His broad publishing activity deserves particular attention: he wrote the first textbook in pharmacology in Serbian with an original chapter on hormones, the first of its kind in Serbian pharmacotherapy. He was highly dedicated to teaching -everyone was afraid of "Professor Bogdanovic's index finger," which would point out the mistakes of younger associates during the prescription exercises. His exams were like theatrical performances that have been remembered for a long time. He often examined students from various faculties at the same time: medicine, veterinary medicine and others. Professor Bogdanović talked to doctors, students and laypeople equally clearly and vividly. He sent his younger associates for training to the world's leading centres and carefully pursued personnel policy. 11

Conclusion
It is difficult to remain indifferent to the picture of the rapid development of pharmacology at the Faculty of Medicine in Belgrade. The professors mentioned with the most profound respect in this text have brought us closer to world science without sparing themselves and often sacrificing their entire lives to it. Their example inspires and obliges us today, not only now when our faculty is celebrating a centennial anniversary in the turbulent region of the Balkans.