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Prof. dr Ivan Berkeš

Professor Ivan Berkeš, an important figure in the field of pharmacy and medicine, was the founder of medical biochemistry and clinic enzymology ([1]) in the health care of Serbia and Yugoslavia. Under his guidance, many generations of medical biochemists were educated at the Faculty of Pharmacy in Belgrade, and for a long time there was no laboratory in Serbia that did not employ one of Prof. Berkeš’s students. Prof. Berkeš founded Serbian medical biochemistry and established it as a scientific and health discipline. His work will live on through these and the future generations of medical biochemists, who remain eternally grateful and promise to honor his memory with love and respect.

Prof. Dr Ivan Berkeš was born on November 13th, 1910, in Bjelovar, where he was educated at the Classical Gymnasium (studying Latin and German for 8, and Greek for 6 years). In 1933 he graduated from the Department of Pharmacy of the Faculty of Philosophy in Zagreb. It should be mentioned that he completed his internship at the Pharmacy of Stanislav Ilakovac in Zagreb, having taken the following classes during the course of his studies: Physics with Prof. Hondl, Botany with Prof. Vouk, Chemistry with Prof. Bubanovic, Pharmacognosia with Prof. Vrgoc, Pharmaceutical Chemistry with Prof. Fluniani and Pharmaceutical Technology with Prof. Benzinger. In 1936 Ivan Berkeš also graduated from the 7th group of Chemistry (a. Chemistry, b. Experimental Physics, c. Physical Chemistry, Higher Mathematics, Mineralogy and Botany) at the Faculty of Philosophy in Zagreb.

Ivan Berkeš obtained a doctorate in philosophy (namely, chemistry) in 1939 at the University in Zagreb. That same year, he was elected as an assistant at the Chemical Institute of the Faculty of Medicine, whose head at the time was Prof. F. Bubanovic. In 1941, Dr Ivan Berkeš was dismissed from employment and the following year imprisoned at the concentration camp Kraljevica-Rab. From 1943 to 1945 he was actively involved in the National Liberation War. After the war, between 1945 and 1947 Dr Ivan Berkeš held various functions at the state Institute of Chemical-Pharmaceutical Production in Belgrade, serving as the assistant director and later director of this Institute. In the period of 1947–1948 he worked as a scientific advisor for the Reparation Committee in Budapest, after which he rejoined the staff of the Institute of Chemistry of the Faculty of Medicine in Zagreb, where he worked until 1953. Between 1953 and 1960 Dr Ivan Berkeš taught at the Medical Faculty in Skopje, where he had been elected as an Associate Professor of Biochemistry. In that period he formed the Biochemical Institute at this Faculty. In 1960 Dr Ivan Berkeš joined the Institute of Biochemistry of the Faculty of Pharmacy in Belgrade. He was elected Senior Professor of Medical Biochemistry in 1964, and remained at this faculty, as a long-term director of the Biochemistry Institute, until his retirement in 1978.

Dr Ivan Berkeš was introduced into the scientific work of the Faculty by Prof. Bubanović’s assistants, with whom he was friends since his third years of studies when he was appointed class demonstrator. Among the assistants, the one who exerted a special influence on Dr Berkeš was Tomislav Pinter, who revealed to him the secrets of analytical and physical chemistry. The help of Miloš Mladenović, later also a Professor at the Faculty of Pharmacy in Belgrade, was particularly valuable in practical work, as he brought him into preparative organic chemistry and Pregl’s micro-analysis (1931). Upon suggestion by Dr Mladenović, Prof. Ivan Berkeš worked on isolating and determining the functional groups of polyterpene acids in a-elemi and b-elemonic acids. This led to the publication of the first papers about the new derivatives of dihydro- and dibromineelemonic acid, and di- and tetraozonide. Ivan Berkeš’s dissertation entitled »An Addition to the Knowledge of Elemi Resin«, Faculty of Philosophy, Zagreb, 1939, is the result of experiments in this field. Together with Dr Pinter he worked on several problems in colloid chemistry and inorganic analytics, the results of which were never completed nor published due to war operations. A study on complex hexacianides was published after the war. Through his work in electrochemical analytics (under the influence of Prof. Tutundžić), where he became acquainted with potenciometry and amperometry, he created a basis for the introduction of electrophoresis into wide practice. This modern technique became a focus of interest for clinical biochemistry after Wunderly and Quhramann popularized free electrophoresis according to Tiselius. Due to financial reasons, especially the practical-routine conditions, it was impossible to use the large and bulky apparatus in clinics and hospital laboratories. Dr Berkeš, therefore, offered several method solutions for paper electrophoresis, one of which he exhibited towards the end of 1950 at a meeting of the Society for Experimental Medicine in Zagreb. The first publication appeared in 1950 in the Medical Newsletter. Thus he became one of the first investigators in this field in the world, and his publications were cited in nearly every monograph dealing with this topic (Block-Durrum, Antwiler, Hais-Macek, Michael Lederer, Ribeiro and Assoc., McDonald), as well as in numerous clinic papers. Along with the methodical success achieved with the patent (apparatuses of such type can still be found in some Belgrade laboratories), a series of clinic papers were published, such as on the application of electrophoresis in liver diseases, myeloma, transudate, exudates, immunologic reactions. Certainly the most interesting is the study of nephritic syndrome in children, where the status was determined by parallel electrophoresis of unconcentrated urine and serum (1952), which was suggested as a differential-diagnostic method. The transition to chromatography of amino-acids from fish protamines (B. Briski) marked the molecular size of these proteins. Continuing efforts to characterize individual protamines from the mixture by using insulin (insulin-protamine) inaugurated the separation of protamines by paper chromatography. Investigations of insulin purity and its dissociations into protomers (with P. Berkes) logically followed. Since the dosing of insulin was highly insecure on tissue carvings in Warburg’s respirometer, an attempt was made to measure biological activity in a suspension of isolated cells (e.g. tumors), but the simplest way seamed to involve yeast. All these investigations were registered in publications where proteins (especially insulin) were proved to have a determined although unspecific influence on membrane transport. This is where Dr Ivan Berkeš’s preoccupation with the composition and structure of the membrane and its transport mechanism originated, which will be the focus of study for his school during the years to come. Upon arriving in Belgrade, Prof. Berkeš worked for several years on projects for the Republic Science Institute of the Federal Republic of Serbia, under the topic »Thiol Function«. First, the highly accurate and specific amperometric titration of free sulphhydryl groups in low-molecular compounds and proteins was introduced. It served primarily for the investigations of carbon disulphide poisoning. The most significant achievement in this domain is the amperometric determination of the activity of enzyme dimethyleethine: homocysteine methylferase (2.1.1.3), which opened a new field of study that was unfortunately never fully expanded and used. When it became clear that clinic investigations of transamination activity can yield useful diagnostic data, at the Faculty of Pharmacy in Belgrade under the guidance of Prof. Dr Ivan Berkeš, Mr Božidar Štraus obtained a doctor’s degree (1962) by examining this phenomenon on erythrocytes. As his mentor, Prof. Berkeš aimed further research at erythrocytes, in the sense of principle involvement of C-4 dicarbonic acids in membrane transport (M. Stanulović, 1966). According to Prof. Berkeš’s conception, these acids have a crucial role in providing energy to erythrocytes as well as in alkaline ions transport through the membrane. Through a series of papers research continued, focused on transamination, transport of certain organic acids through the membrane and their role as substrates (N. Majkić). Beside this, investigations were undertaken regarding respiration with methylene blue, reduction of methhemoglobin into two systems present, as well as the involvement of ATPases in transport. Several of Prof. Dr Ivan Berkeš’s candidates obtained their master’s and doctor’s degrees for their work under this topic, which was part of the project »Investigation of Normal Erythrocyte Metabolism« financed by the Republic Science Institute of the Federal Republic of Serbia. For many years Prof. Ivan Berkeš had a contract with the Institute related to the topic of »Evidence, Determination and Isolation of Blood Enzymes«, where experiments dealing with the determination of the fenotypic distribution of erythrocyte enzymes in populations living on the territory of the Federal Republic of Serbia, as well as certain ethnic groups, were given special attention (the following enzymes were investigated: acid phosphatase, adenilate-kinase, phosphoglucomutase etc.). For nearly 20 years Prof. Ivan Berkeš invested all his efforts into methodological research in clinical biochemistry, general and clinic enzymology. Numerous specialist, master and doctoral theses testify to this fact, and these precisely reflect which problem was prioritized at which time in our community. One should only go through the titles of about 150 specialist papers done under his tutorship or upon his suggestion, to see which topic was in focus. One other noteworthy reference could be made to a doctoral dissertation (N. Majkić) done at the Faculty of Pharmacy and based on the idea of Prof. Ivan Berkeš, which aimed to establish a kinetic method for the determination of a number of oxidases (anaerobic transhydrogenase) based on the oxidation of chromogen ABTS. These experiments later served as a foundation for establishing methods for the determination of a number of substrates (e.g. glucose, cholesterol, alcohol), which evoked much interest on the local as well as the global level. Prof. Dr Ivan Berkeš became interested in enzymes as a biochemistry teacher at the Medical Faculty in Skopje. During his many years of scientific-investigative work, Prof. Berkeš was especially dedicated to examining several classes of enzymes. He was a member of the Enzyme Committee of the International Federation of Clinical Chemistry. As the founder of clinical enzymology, in 1975, together with Prof. Persida Berkeš, he wrote the famous work »General and Medical Enzymology«, the first scientific elaboration of enzymes in our language, nominated by the Faculty of Pharmacy in 1976 as the candidate for the October Prize of the City of Belgrade. Their belief, which they never abandoned, was that metabolism may be understood only with the knowledge of the nature and characteristics of individual enzymes. For that reason, he paved the way for the »Belgrade School of Enzymology« as a pedagogic-publicistic and research entity. During his working years, Prof. Dr Ivan Berkeš published several books and over 200 scientific papers in renowned magazines in Yugoslavia and worldwide. He mentored a series of scientific-research projects, the work continued by his school after his retirement. Immediately after joining the staff of the Faculty of Pharmacy in Belgrade, Prof. Dr Ivan Berkeš became dedicated to creating a program for specialty studies in medical biochemistry. During the 18 years under his tutorship, more than 150 medical biochemists became specialists in this field, and several dozen pharmacists obtained their master’s and doctor’s degrees. Another way of contributing to the development of medical biochemistry was through his active engagement in the Federal Committee for Medical Biochemistry and the Section of Medical Biochemistry of the Pharmaceutical Society of Serbia as a professional organization. Owing to his many active years as a scientist and expert, Prof. Dr Ivan Berkeš helped to establish medical biochemistry as a contemporary diagnostic branch in Serbian medicine and pharmacy, whereby the professor unselfishly shared his vast knowledge with his students, interns and postgraduates.

"To us, students and followers as they say, Prof. Berkeš was at the same time a professor, a Teacher, a father and a friend. He taught us the secrets and skills of medical biochemistry, but also the life’s truths. He appreciated and supported open-mindedness, courage and determination in young people, encouraging students to develop a spirit of investigation. We loved listening to his lectures, because of his illustrative approach to serious matters. His witty remarks still come to mind, recorded in the texts of our master and doctoral theses and specialist papers. We never repeated the same mistakes. He inspired us to reach for the truth, but also to achieve the impossible. Prof. Berkeš was a versatile figure – he loved music, painting, spoke five languages, knew history, philosophy. He practiced philately for many years. He was a row model to his students in every respect. Our secret wish to have a hint of his charisma. We honored, admired and respected him. These feelings will always live within us."

In Belgrade, November 16, 2010 Prof. Dr Nada Majkić-Singh


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