Vladimir Sergeevich Gulevich (; 18 November 1867 – 6 September 1933) was a Russian and Soviet biochemist, one of the founders of Russian biochemistry. He spent most of his career at Moscow State University, where he became full professor and head of medical chemistry and served as rector for several months in 1919.

Working with his students and collaborators, Gulevich was the first to isolate the dipeptide carnosine and the compounds carnitine and methylguanidine from mammalian muscle, and he played a major role in the development of medical chemical analysis and biochemical education in Russia.

Biography

Family background and early interest in chemistry

Gulevich was born in Ryazan into the family of a teacher. His father, Sergei Vikentyevich Gulevich (1843–1901), came from a family of teachers, graduated from the historical and philological faculty of Moscow University in 1866 and made a rapid career in secondary education, eventually becoming director of the 2nd Moscow Gymnasium and receiving hereditary nobility for his service. His mother, Anna Ivanovna (née Pavlinova, 1849–1939), belonged to the nobility.

The 2nd Moscow Gymnasium, which Sergei Gulevich headed for many years, was considered one of the most prestigious in the city; among its pupils were the chemist Ivan Kablukov, geologist Alexei Pavlov, biochemist Alexander Oparin and other future scientists. Both of Vladimir's surviving siblings — he and his younger sister Tatyana (1869–1951) — studied there; Tatyana later worked as a feldsher and pharmacist.

According to his autobiographical notes, from the sixth class of the gymnasium Gulevich "showed a particular inclination for chemistry" and set up a small home laboratory, where he performed simple experiments using popular chemistry books as a guide. This early fascination determined his choice of university studies.

Education and doctoral research

In 1885 Gulevich entered the medical faculty of the Imperial Moscow University, which he graduated from in 1890 with distinction as a physician. While formally a medical student, he specialised in chemistry, first working in the laboratory of Aleksandr P. Sabaneev at the faculty of physics and mathematics, where he completed courses in qualitative and quantitative analysis, and then in the laboratory of Aleksandr D. Bulyginsky at the Department of Medical Chemistry, where he studied organic and biological chemistry.

In his fifth year he wrote an essay on "The origin, development and role of giant cells in pathological processes" under the supervision of pathologist Vasily Shervinsky; this work was awarded the university gold medal. After graduation he was retained at the Department of Medical Chemistry to prepare for a professorial career and from February 1891 worked there as an extra-staff laboratory assistant.

Supported by a ministry stipend, Gulevich carried out research on choline and neurine in brain tissue. His doctoral thesis, On choline and neurine. Materials for the chemical study of the brain (defended in April 1896), combined an exhaustive critical review of the literature with detailed experimental work. He showed that neurine was absent from the brain under normal conditions and concluded that the then popular theory attributing certain mental illnesses to self-poisoning of the brain by neurine was unfounded.

Overseas training and work with Albrecht Kossel

In early 1898 Gulevich was sent abroad on a two-year study trip funded by the Ministry of Education. On his way to Germany, he briefly visited Warsaw, Vienna, and Prague to inspect university laboratories and observe local teaching practices. He later wrote that, compared with Moscow, medical chemistry in many European universities was taught with fewer lecture hours and without obligatory laboratory work, which in his view hindered effective training.

The main goal of his trip was to work in the laboratory of Albrecht Kossel at the Physiological Institute of the University of Marburg. Kossel was then a leading authority on nucleic acids and proteins, and under his supervision Gulevich developed improved methods for isolating and purifying arginine, including preparation of new silver salts and determination of their optical rotation, and identified thymine among the products of protein and nuclein hydrolysis using both chemical and crystallographic analysis. He also studied the action of trypsin on organic substances in an attempt to clarify which types of bonds in proteins are most susceptible to enzymatic cleavage.

While in Marburg, Gulevich attended Kossel’s lectures and observed student practicals. He later criticised the very limited laboratory time and lack of prior training in basic qualitative analysis among German medical students, and this experience reinforced his conviction that biochemistry teaching should be built upon a solid foundation of general and analytical chemistry.

Between 1898 and 1900, during and immediately after his stay abroad, Gulevich published sixteen research papers and a book, most of them in German journals such as Zeitschrift für physiologische Chemie, edited by Kossel.

Kharkiv professorship and the discovery of carnosine

From July 1899 to December 1900 Gulevich was extraordinary professor of medical chemistry and physics at the medical faculty of the University of Kharkiv. On arrival he found the laboratory poorly equipped and set about reorganising and refitting it, while at the same time lecturing and supervising students.

In Kharkiv Gulevich began a new line of research on the so-called extractive substances of skeletal muscle. Building on earlier work on meat extracts by Justus von Liebig and others, he reasoned that the nitrogen content of known muscle constituents did not account for the total nitrogen in extracts and that new nitrogen-rich compounds likely remained undiscovered. Using a method of precipitation with phosphotungstic acid followed by treatment with silver nitrate, he and his student Semen Amiradjibi isolated in 1900 a new strongly basic substance of composition C9H14N4O3, which they named carnosine.

Subsequent work showed that carnosine is a dipeptide, β-alanyl-L-histidine, and that it is characteristic of striated muscle: it is abundant in skeletal muscle but essentially absent from liver, kidney, spleen, blood, lung and other tissues. This first natural β-amino acid derivative attracted considerable interest and marked the beginning of systematic studies of muscle extractives in Gulevich’s laboratory.

Return to Moscow and later career

In December 1900 Gulevich was elected to the chair of medical chemistry at the Imperial Moscow University. In 1901 he returned there as extraordinary professor and in 1904 was promoted to full professor; after the death of Bulyginsky in 1907 he became head of the Department of Medical Chemistry.

Over the next few years he expanded and modernised the departmental laboratory, making it one of the best-equipped biochemical laboratories in Russia. Between 1904 and 1907 nine of his papers, most of them published in Zeitschrift für physiologische Chemie, reported the discovery of two further nitrogenous compounds from muscle: carnitine (1905, with R. P. Krimberg) and methylguanidine (1906). These studies, carried out together with his students, laid the foundations for the chemical and comparative biochemistry of muscle.

In addition to his work at Moscow University, Gulevich taught biological chemistry at the Higher Women's Courses in Moscow (1908–1918), where he organised a biochemical laboratory and practical classes, and organic chemistry at the Moscow Commercial Institute (from 1910), where he headed the Department of Organic Chemistry and a laboratory oriented towards industrial and technical applications.

Within the university he also held a number of administrative posts: he was vice-rector (1906–1908), dean of the medical faculty (1918) and acting rector from January to March 1919, during a politically turbulent period in the history of the institution.

From the 1920s he worked in the laboratory of physiology and biochemistry of animals at the All-Union Institute of Experimental Medicine, and shortly before his death he became head of its biochemistry section.

Gulevich died in Moscow on 6 September 1933 from a rapidly progressing malignant tumour and was buried at Novodevichy Cemetery.

Scientific work

Gulevich’s research covered several interrelated areas: nitrogen metabolism, the chemistry of amino acids and proteins, and the biochemistry of muscle tissue. A recurring theme was the chemical characterisation of low-molecular-weight "extractive" substances present in small amounts but with important physiological roles.

Muscle extractives and dipeptides

Beginning with his work in Kharkiv and continuing in Moscow, Gulevich and his collaborators systematically investigated the extractive substances of muscle. After the discovery of carnosine in 1900, they identified carnitine (vitamin B11) in 1905 and methylguanidine in 1906, determined their structures, distribution in different muscles and species, and conditions of enzymatic breakdown.

His laboratory also became a centre for comparative biochemistry. Students and co-workers examined the presence or absence of carnosine and carnitine in the muscles of various animals, demonstrating, for example, their occurrence in the muscles of cattle, horses and sheep and their absence from a number of non-muscular tissues. In 1928 N. F. Tolkachevskaya, working under Gulevich’s supervision, isolated from poultry muscle a related dipeptide, anserine, which together with carnosine became the subject of later physiological studies.

These investigations helped to establish the roles of carnosine, carnitine and related compounds in muscle energy metabolism and acid–base regulation and influenced subsequent work in muscle biochemistry.

Amino acids, proteins and methods

Beyond muscle extractives, Gulevich worked on the synthesis and properties of amino acids and proteins. He proposed a method for synthesising amino acids by electrochemical reduction of esters and studied degradation pathways and structural features of amino acids and protein hydrolysates.

A strong methodological orientation ran through his work. Gulevich argued that progress in biological chemistry depended critically on the development and adoption of precise experimental methods — not only strictly chemical but also crystallographic and physico-chemical. He believed that many earlier results obtained with crude techniques were unreliable and that new methods would make it possible to isolate and characterise individual compounds from previously amorphous groups of "extractive substances".

Medical chemical analysis

Gulevich is often regarded as the author of the first Russian handbook on medical chemical analysis. His Analysis of urine. A guide for practical work in the laboratory, first published in 1900 in Kharkiv and repeatedly reissued in Moscow throughout the early twentieth century, served for decades as a standard manual for physicians and students learning clinical chemical methods. He also edited a Short course of biological chemistry based on his lectures, prepared by his student I. A. Makeev.

In the 1920s, at the Moscow Institute of National Economy (formerly the Commercial Institute), his laboratory worked on applied chemical problems such as the production of pharmaceutical compounds, including the local anaesthetic holocaine, chlorination and nitration of aromatic compounds for industrial use, utilisation of sugar-industry by-products, hydrolysis of casein for the manufacture of bouillon cubes and the preparation of calcium glycerophosphate.

Teaching and mentoring