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by Boris VANYUSHIN, Corresponding Member of the Russian Academy of Sciences, A. N. Belozersky Institute of Physico-Chemical Biology, M. V. Lomonosov Moscow State University

The discovery of nucleic acids is certainly among the ground-breaking events in the 20th-century natural science. It is these compounds, not proteins (as believed earlier), that proved to be responsible for heredity. DNA sequencing has provided an insight into the workings of the genetic code and mutations. The now state-of-the-art technique of targeted cleaving (cutting) and joining (ligation) of DNA molecules has made it possible to design essentially novel genes and genomes. Following in the footsteps of molecular biology are new intriguing areas of knowledge, e.g. genomics, proteomics, bioengineering, bioinformation science, genosystematics and the like. The present-day molecular biology has seen many ups and downs along its path. And one of the men who stood at its cradle and reared it was the brilliant Russian biologist Andrey Nikolayevich Belozersky, one of the pioneers and world leaders in the study of nucleic acids. Today we are paying tribute to him on his birth centennial...

Back in the early 1930s Assistant Professor Belozersky took up a new class of natural compounds, the nucleic acids, at the suggestion of his teacher, Prof. Alexander Kiesel, who had organized the Department (Chair) of Plant Biochemistry at Moscow University. Two types of nucleic acids, different in their chemical structure, had been identified by that time: RNA (ribonucleic) and DNA (deoxyribonucleic) ones. Isolated as they were from two stock materials - yeast (RNA) and calf thymus (DNA), they were at first called yeast and thymonucleic acids, respectively. The former one (RNA) was thought to be proper to plants only, while the latter (DNA) - to animals. It was Andrey Belozersky who dashed that fixed notion by detecting "animal" DNA in plants, he did it in chemically elegant and cogent experiments by isolating thymine, a nitrogen base typical of DNA, from pea seedlings and describing it. In 1934 the news spread all over the world scientific community: the results of his work were published in the most authoritative science information periodical of the time, the Hoppe-Seylers Journal of Physiological Chemistry (Hoppe-Seylers Zeitschrift fur Physiologische Chemie) of Germany. As Belozersky proved it thereupon, that was not a chance incident: along with RNA, DNA was

Pages. 83


an obligatory component of the plants he had studied (he detected thymine in soya and kidney beans, in horse chestnut seed, in lime buds, onion bulbs, in cedar and wheat germs).

Even though the functional role of nucleic acids was still an enigma, it became clear that DNA was a nuclear material present within chromatin and chromosomes. These findings distilled into an epoch-making discovery of the century: about the unity of the genetic material of the animal and plant kingdoms.

In his subsequent studies Belozersky showed it abundantly clear: that different microbes always carry both types of nucleic acids and that microorganisms contain high amounts of them due to growth and reproduction peculiarities. The results of these studies were condensed to an article in the Proceedings of a Symposium at Cold Spring Harbor, USA, just before the notorious session of VASKHNIL (National Academy of Agriculture of the USSR) in August 1948 that tore to pieces our genetics school. The very publication of the article at that ill-starred time embarrassed Belozersky, what with the rabid drive launched in this country against "cosmopolites" and geneticists; he seemed to be a good sitting duck for foul abuse at his home university from a bunch of well-wishing "knockers" whose weak spot fortunately was that they had never heard anything about nucleic acids and apparently had no command of English either. That saved Belozersky.

Getting down to nucleoproteins (complexes formed between nucleic acids and proteins), Belozersky incubated the idea about the different tightness of bonding between proteins and nucleic acids. This idea drew attention from Mikhail Prokofiev, a talented chemist demobilized from the army with war's end; both men joined hands at Moscow University's Department of Chemistry (today this line of research is being carried on with much success by Acad. Alexey Bogdanov). Thus, at this stage Dr. Belozersky conceptualized a new research trend that married

Pages. 84


biology and chemistry. In 1950 he and Harry Abelev (elected to the Russian Academy of Sciences in 2000), obtained important results by isolating (and characterizing) the nuclear protein histone from plant nucleoproteins and thus proving its obligatory presence in plants and animals alike. Hence followed the conclusion about the structural unity of their nuclear material organization. Prof. Belozersky was the first to demonstrate that nucleoproteins contain both histone and nonhistone proteins, which is now a commonly accepted fact (nonhistone proteins as part of the nuclear chromatin are implicated in gene functioning).

As of the mid-1950s Dr. Belozersky and his pupils - Alexander Spirin (elected to the Academy of Sciences in 1970)*, Boris Vanyushin, Sofia Uryson, Andrey Antonov and others-became involved with the characteristics of nucleic acids in different organisms. Since in those days the only way of studying the specificity of such compounds was to determine their composition, Dr. Belozersky and colleagues had, to begin with, to find the ratio of constituent elements (nitrogen bases) in various DNAs. The very first studies of DNA isolated from microbes, plants and animals demonstrated: that the DNA molecule, insufficiently explored though it was at the time, is species-specific in its composition, and this character is of clear taxonomic significance (these works by Dr. Belozersky and his school have laid a groundwork for genosystematics).

Making comparative studies of bacterial DNAs and RNAs, Drs Belozersky and Spirin came up with yet another major discovery: that RNAs correlated with DNAs, which means that at least some part of RNA within the cell is a replica of DNA. Thereby the existence of informational (messenger) RNAs was predicted. Francis Crick (Nobel Prize, 1962) said this prediction played an exceptional role in the progress of molecular biology, for it spurred biologists in many countries to look for mRNAs detected shortly afterwards.

While studying the composition of all the various DNAs, Drs Belozersky and Vanyushin (author of the present article) saw that alongside the four regular bases these complex molecules might also contain small amounts of other, additional ("rare") bases formed via modification (methylation) of the standard nitrogen bases in DNA chains. They discovered the different tissue (cell)-related degree of DNA methylation in animals and in plants,


See: A. Spirin, "Challenges of Contemporary Biology", Science in Russia, No. 2, 2001. - Ed.

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and found that in different cells of one and the same organism the DN A molecule is modified differently. And thus they pioneered in formulating the idea about DNA modification (methylation) being connected with cell differentiation as a gene expression regulator. These findings furnished mainly a basis for a new discipline, epigenetics. It is common knowledge today that DNA methylation, in which special enzymes (DNA methyltransferases) are implicated, is one of the signals that control the functional activity of genes. More than that, Drs Belozersky and Vanyushin showed that DNA methylation changes with age, and its distortion portends cancer. This conclusion paved the way for an essentially new approach to the diagnostics and treatment of oncological diseases.

Andrey Nikolayevich Belozersky also showed interest in other cellular compounds like proteins and polyphosphates, and in antibiotics, too. His joint work with Dr. Igor Kulayev (elected to the USSR Academy of Sciences in 1987 as corresponding member) in studying the ultrastructure, characteristics and metabolism of inorganic polyphosphates meant a world contribution in understanding their role in the vital activity of organisms, and enabled scientists to address these compounds not only as a unique pool of phosphoric acid resides accessible for use but also as specific regulators of many biochemical processes within the cell, including those controlling nucleic acid synthesis and gene expression. Drs Belozersky and Tatiana Paskhina, all the way back in the 1940s, studied the structure of gramicidin С (gramicidin S, Soviet gramicidin), one of the first antibiotics obtained in this country. Drs Belozersky and Irina Naumova accomplished brilliant works in studying teichoic acids* isolated from the cell wall of actinomycetes.** And in the early 1960s, together with Dr. Galina Zaitseva, Belozersky studied the immunogenic characteristics of pathogenic bacteria as well as polysaccharides in the nitrogen-binding bacterium, azotobacter.

Dr. Belozersky was certainly right in thinking that plant protein studies were kept down in our country, and therefore he invited an eminent biochemist, Dr. Vadim Spikiter of the Institute of Biological and Medical Chemistry (USSR Academy of Medical


* Teichoic acids - structurally complex compounds composed of sugars, alcohols, amino acids and phosphoric acid, and incorporated within the cell wall of gram-positive microbes. - Ed.

** Actinomycetes - microorganisms which belong to the order of Actinomycetales. Their body resembles a mass of branched, thin, nonseptate filaments, the hyphae. About 700 species of A. are known to date, with many antibiotics among them. - Ed.

Pages. 86


Sciences), to work with him at Moscow University. These studies have been continued at Moscow University by his son, Prof. Mikhail Belozersky.

Dr. Belozersky could aptly combine his multifarious research interests working both for Moscow State University and for the Academy of Sciences of the USSR, though he never spread himself thin. His passionate involvement brought him a prestigious Lomonosov Prize; in 1962 he was elected to the Academy of Sciences as full member (Academician) and in 1971, became its Vice-President (and acted in this capacity up until his untimely death in 1972). But he never wavered in his loyalty to his Alma Mater, Lomonosov Moscow State University. For a long time Dr. Belozersky was in charge of its Department (Chair) of Plant Biochemistry, succeeding his famous predecessors, Prof. Alexander Kiesel and Acad. Alexander Oparin.

Andrey Nikolayevich Belozersky was born in Tashkent on August 29, 1905. His grandfather had moved from heartland Russia to Central Asia with the mission of converting Moslems to Orthodox Christianity. A freak of fate transplanting the Belozersky family roots to Tashkent!

Still in his young days Belozersky worshiped his Moscow teacher, Alexander Kiesel, who invited him from Tashkent to the University of Moscow, first as a visiting student and then, taking a hard second look, offered a job at the newly established Department (Chair) of Plant Biochemistry as a junior member of the research staff. The professor proved to be captious and exacting with regard to Belozersky in particular. The young scientist wondered at first, why all the other students used titrants (titrated solutions) in their experiments while he had to prepare titrants of alkalis from metal sodium.

Only later did he realize: his teacher was taking his measure, sizing him up. Shortly before his arrest on false charges late in 1941, Prof. Kiesel wrote this in Belozersky's reference: "As his older comrade in higher school teaching and as head of the department at which he is working, I should give him top marks both as a researcher and teacher, and as a good man, too."

It's just inconceivable that in those times you could count them on the fingers of one hand-them who were involved with nucleic acids the world over. There were three standouts among them: Andrey Belozersky in Russia, John Davidson in Britain, and Erwin Chargaff in the United States. Though separated by seas and state borders, they were no strangers in this world. Even in the cold war years, contrary to official directions, Belozersky would easily come together with people akin in nature and science, such as

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Erwin Chargaff*, Severo Ochoa**, Marianne Grunberg-Manago***, Seymour Cohen****, and others. We, Belozersky's pupils, saw it clearly there could be no frontiers for true scientists. His friendship with the great men of science infected us somehow. While staying at Cambridge, England, as visiting researcher in 1964, I had Roy Markham as my supervisor, a scientist known for his works on the structure of RNAs and plant viruses. Like most of the English he showed a cautious and skeptical attitude towards the "Soviets". Yet, all political travails notwithstanding, the very name of the Belozersky school was a hallmark of bona fide dedication to science. Introducing me, a raw beginner in biochemistry from Moscow, to his colleagues, Roy said: This young man is a pupil of Belozersky's, the same one who discovered DNA in plants...

I admired Belozersky's lectures, not at all academic or meant for the gallery, but quite confidential and thrilling. He loved his students, not to speak of pupils, and they replied in kind. I recall one freak incident back in my college days. Once on a short night in June I kept playing volleyball on campus up until daybreak and showed up at our practicals only about noon. Our tutor, Assistant Professor Grigory Serenkov, turned me out of doors - don't come back without permission from the chief, that is Acad. Oparin. Since he happened to be out, I went to professor Belozersky. As I saw his kind, intent eyes sparkling with mischievous flashes, I felt I could tell no lies and laid it out as it was - I had overslept, period. The professor blew up. "But this is outrageous! What you need is a good stiff broom to chase you away!" It was his pet dictum, though the Russian idiom speaks of a clean sweep with a "foul broom". Calming down in a while, he flashed a kind smile. "Well, as a matter of fact, I'm quite envious of you, Boris." That was his makeup - a good amiable man and priceless teacher he was.

Andrey Nikolayevich never foisted his opinion on others or forced them to do this or that. He would always look into the heart of the matter and was delicate in articulating his stand. Many turned to him for advice and consultations, with requests for help in mastering this or that research method. He never said no, though with certain reservations: yes, he would go ahead and help, but only if he managed (!) to persuade his coworkers to take part. We needed no orders, sure, but rushed to help those people out. Many of such "volunteers" evolved into eminent scientists performing fine in various republics of the former Soviet Union.

His boyish ardor and zest was amazing, it knew no bounds and made him


* Erwin Chargaff - American biochemist who had determined a composition (ratios) of purine and pyrimidine bases in DNA molecules and showed species-specificity of DNAs. - Ed.

** Severo Ochoa - American biochemist elected to the Academy of Sciences of the USSR as foreign member (1966). He has made a big contribution in breaking the genetic code of nucleic acids and in elucidating the mechanism of their biosynthesis. Jointly with Arthur Kornberg of the United States, too, he merited a Nobel Prize in physiology (1959). - Ed.

*** Marianne Grunberg-Manago - French biochemist, elected to the Academy of Sciences of the USSR as foreign member (1988). She was born in Petrograd (St. Petersburg). President of the International Biochemical Union in 1982 to 1988. Her works deal with synthesis of polynucleotides and mechanisms regulating the activity of the genetic apparatus of microorganisms. - Ed .

**** Seymour Cohen - American biochemist who has studied RNA structure. - Ed.

Pages. 88


lay himself out. Not only in science alone. He admired ballet and said he was among the "Semenova regiment", that is with devotees of the great Russian ballerina Marina Semenova, and tried to miss none of the ballets where she was dancing. He loved beauty everywhere and had a refined palate for art. In the last years of his life Belozersky was carried away by the art of Russian miniatures which happened to be on the way out. This interest prodded him to take up Russian history in good earnest where miniature was part and parcel of our fabric, and he took much pride in our roots.

In spite of his enormous workload and high position at the Academy of Sciences and Moscow University, Andrey Nikolayevich Belozersky was always accessible to those who needed him. Every now and then, tired of the routine treadmill in the line of his administrative duties, he would step into a laboratory for a breath of fresh air. Asking the experimenters about their affairs, he envied them in his heart of hearts. "You should know more and do better than I," he used to say to his pupils. This life rule of his obliged us, his pupils, a good deal.

Acad. Belozersky showed much regard for his pupils and never abandoned them. He felt sorry when some of his coworkers had to leave. He took it hard when failing to keep Dr. G. Abelev in the fold: an ordinarly professor at the time, Belozersky was unable to get over secret directives and injunctions of the Soviet personnel policies in those hard times. But he would go out of his way to protect and shelter capable and decent people, never regarding them as would-be rivals but as good colleagues and members of the fraternity who could carry on the cause of his life.

The yardstick of any scientist is in his personal contribution and in his following, a school he leaves. A brilliant name in science may have no active followers, either due to a peculiar character makeup or unwillingness to waste precious time on others.

But this does not hold for Andrey Nikolayevich: even becoming a researcher of world renown, he devoted himself whole-heartedly to his pupils. Eager to give of his generous soul, his lively interest and broad knowledge, Belozersky could not do it to the full limited that he was by the number of vacancies at his department. Changes for the better came only in the very last years of his life.

The A. N. Belozersky school is well known throughout the world, it lives on, grows and carries on the glorious traditions of its teacher. This school is alive in the Department of Molecular Biology, it lives on in the Department of Virology and in the A. N. Belozersky Institute of Physico-Chemical Biology-he has founded both at his Alma Mater, M. V. Lomonosov Moscow State University.

Orphus

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