PRIORITIES OF BIOLOGY

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By Academician Vladimir SHUMNY, Institute of Cytology and Genetics, President of the Associated Academic Council on Biological Sciences, Siberian Branch of the Russian Academy of Sciences (SB RAS)

 

Up until 1957 the West-Siberian Branch of the USSR Academy of Sciences had only two biological research institutes - the Medicobiological Institute and the Central Siberian Botanical Gardens. Today SB RAS has as many as eleven: five in Novosibirsk, two in Krasnoyarsk, and the other four - in Irkutsk, Kemerovo, Ulan-Ude and Yakutsk, respectively. What is their range of problems?

 

Siberia's biological resources are truly immense and are of extraordinary significance for our country, of no less significance than its mineral wealth. However, depleting the available oil and gas reserves, we are doing but little towards the rational use of renewable resources, woodlands in the first place. But these - given scientifically substantiated standards of exploitation and high degree of wood processing - may in time become even more significant than oil and gas. Today Siberian forests occupy an area of about 300 mln hectares (or 750 mln acres) and are a very large component of the earth's biosphere: they generate oxygen, regulate the carbon balance, impact the climate and thus in the long run affect the " health" of our planet and its "mean temperature". But forests are also an industrial object (in Siberia their reserve makes up 35 bin m3, with as much as 100 mln m felled each year). That is why the V. N. Sukachev Forestry Institute (in 1959 affiliated with the Siberian Branch of the USSR Academy of Sciences and moved from Moscow to Krasnoyarsk: today it is under the wing of SB RAS) has for many years been taking stock of local forests and monitoring their condition* in a variety of ways, remote analysis including, and has been making exploitation forecasts.

 

 

* See: V. Sukhikh and V. Zhirin, "Forests Are Seen Better from Outer Space". Science in Russia, No. 3, 2007. - Ed.

 

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Other resources - plant*, animal and soil ones - are just as important. Taken together they constitute an integral ecosystem located in areas of most extreme conditions (the permafrost zone alone accounts for about 35% of Siberia's territory): that is why this ecosystem is highly vulnerable, what with the ongoing climatic changes and increasing anthropogenic pressure. It needs constant control and monitoring. For all its diversity the biological potential has to be used sparingly and reproduced at its best, that is by observing natural laws and relying on scientific achievements. Otherwise we may leave a barren wasteland after us.

 

SB RAS research institutes regard it as their priority objective a steady monitoring of bioresources under everchanging conditions, and that coupled with prognostic assessments and proper utilization technologies. In Siberia as much as 200 mln ha (or 500 mln acres) are good for land- and stock-farming (with less than 15% in use). But this is not to mean that these tracts should be plowed up, something that could touch off an ecological disaster: as a matter of fact, Siberian forest-steppes and plains (steppes) are an excellent fodder base for flocks and herds, a trade practiced by colonists from European Russia for ages.

 

SB specialized research centers working in different parts of Siberia are doing an important job by keeping

 

 

* See: V. Sedelnikov, "Siberia's Plant Kingdom", Science in Russia, No. 3, 2006. - Ed.

 

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Siberia's forest resource.

 

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tabs on the conditions of various elements of the natural complex and their involvement in sustaining the biosphere's stability. And yet carried away by the latest ideas of the contemporary natural sciences, we tend to underrate the essential part of basic scientific activities (though it is important to develop new progressive trends in biology, of course). So basic science is another priority area in the work of our research institutes. Their achievements hold a key to such challenges of the twenty-first century as incurable diseases, the food problem aggravated by the global population explosion, ecological pollution, biosecurity, alternative power sources, and many other things.

 

Understandably already at its initial stage the Siberian Branch of the national Academy of Sciences set up a string of specialized biological research centers: at first it was the Institute of Cytology and Genetics; then came the Institute of Bioorganic Chemistry, reorganized in 2003 into the Institute of Chemical Biology and Fundamental Medicine (at first it was headed by Acad. Dmitry Knorre; its present head is Acad. Valentin Vlasov). The Institute of Biophysics was established in due course at Krasnoyarsk (its first head was Acad. Iosif Hitelson, and its present head is Andrei Degermendzhi); the city of Irkutsk got the Institute of Physiology and Biochemistry of Plants (first headed by Feodor Reimers, corresponding member of the USSR Academy of Sciences, then by Riurik Salyaev, RAS corresponding member, and now by Doctor of Biology Victor Voinikov).

 

And now more about our Institute of Cytology and Genetics (ICG) founded in 1957 under the wing of the Siberian Branch of the USSR Academy of Sciences. Its first head was Nikolai Dubinin, corresponding member of the Academy of Sciences (elected as full member in 1966). It would be in place to recall that since throughout the twenty preceding years genetics as a science had been actually banned, ICG had a tall order before it, namely it had to start research from scratch in all basic lines of classical genetics and demonstrate the efficacy of its methods thereby. Simultaneously it had to begin training young geneticists at Novosibirsk State University.

 

We were having it very hard indeed as the first officially established genetic research center: the ideas of Acad. Trofim Lysenko still held sway - he denied the chromosomal theory of heredity and persecuted its adherents. Nikolai Dubinin, the organizer and first head of ICG, could stay on as director for two years only: in November 1959 he was dismissed on personal instructions of Nikita Khrushchev, First Secretary of the CPSU Central Committee and Chairman of the Council of Ministers of the USSR. Dubinin was blamed by Lysenko and his ilk as a supporter of "idealistic" views of August Weismann, the German zoologist and evolutionist, and of the American biologist Thomas Morgan (Nobel Prize, 1933).

 

N. Dubinin was replaced by his deputy, Dmitry Belyaev (elected to the national Academy of Sciences as corresponding member in 1964, and in 1972 as full member). As ICG director he had to bear the brunt of the work to keep the still young research center going. D. Belyaev continued as ICG head for over twenty-five years and made ICG into a foremost research center in this country and abroad. He had to face many hardships. Up until 1964, ICG had been pecked by sundry commissions seeking to close it down or pull it into line with Lysenko's dogmas. The director and the young research

 

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New method of obtaining an antiflu vaccine devised at the Institute of Chemical Biology and Fundamental Medicine (SB RAS).

 

collective could hold their ground only due to vigorous support from Acad. Mikhail Lavrentyev and his colleagues - eminent mathematicians, physicists, geologists and chemists.* We owe them great thanks.

 

ICG has fulfilled its research program mapped out at the very beginning. In basic research it obtained results of global significance. May I cite a few examples.

 

Dmitry Belyaev and Liudmila Trut (now Doctor of Biology) have created a domestication model for animals (that is adapting, taming or developing them for man's use). Their behavioral selection (according to quiet behavior and contact with man) has revealed a vast variability potential. Thus, it became possible to reproduce the domestication pattern, especially its initial stage in 50 generations (50 years) of foxes, while under natural conditions this would have taken thousands of years. Today this model has been adopted by homeland and foreign researchers - from molecular biologists to evolutionists - exploring into behavioral mechanisms of animals.

 

Dr. Ilya Kiknadze and colleagues, cooperating with their counterparts abroad, have studied chromosomal changes of the chironomus mosquito on different continents. They came to a global conclusion that inversions (a 180° turn of part of the chromosome) and translocations (with one part of the chromosome moving to another one) are playing a substantial role for speciation not only in insects alone but in other living beings as well, since this involves transposition (rearrangement) of genes in chromosomes.

 

Our research scientists have a good record of achievement in the field of molecular and general cytogenetics of animals and plants, too. They have obtained unique substituted and supplemented lines in grasses. Say, rye chromosomes were substituted for some of the chromosomes in the genome of wheat, which made it hardier in winter- and salt resistance, and increased the protein content in the wheat grain.

 

Using bioengineering techniques, our Institute has realized technologies for transferring separate chromosomes or even their parts from one plant or animal variety to another one; this produces genetic material unique in many characteristics.

 

Dr. Alexander Grafodatsky and coworkers, proceeding from the results of human genome sequencing, have localized (superposed) samples of human chromosomes on chromosomes of 45 representatives of all mammalian orders, something that allowed to identify homologous (similar) sites of these elements of heredity by comparing them with identical sites in Homo sapiens. This has been the very first reconstruction of the probable genomic structure in the mammalian ancestor, a very important thing for understanding the evolution of different species and life in general.

 

Acad. Igor Zhimulev has obtained breakthrough results of global significance in the field of molecular cytogenetics by studying chromosomes in a classical object - the Drosophila fly. He detected a new gene in it controlling replication (self-reproduction) of chromosomal DNA. He demonstrated that "silent regions" of DNA, which make up a large part of the genome, are composed of unique genes organized in clusters by the coordination principle. As soon as a signal is on, the silent clusters of genes are activated, i.e. their silence is but temporary.

 

 

* See: N. Dobretsov, "First Regional Branch", Science in Russia, No. 4, 2007. - Ed.

 

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Reconstruction of the most probable structure of 45 species from the mammalian order (mammalian ancestor genome).

 

Gene engineering is developing space, especially what concerns the technology of transferring individual genes from one organism to another, regardless of their taxonomic relatedness. This opens up fantastic opportunities in studying the performance of genes and in creating new models for explaining their functional mechanisms. Here are just two examples of what our researchers have accomplished here.

 

Dr. Nikolai Dygalo and coworkers have blocked a gene responsible for the number of noradrenaline* receptors. Thereby it became possible to increase the expression of another gene controlling the synthesis of an enzyme triggering the process of adoptosis (genetically pre-programmed death, "suicide" of cells). These experiments demonstrate the possibility of regulating the activity of genes and even switching some of them off (knocking them out). Many laboratories of the world have created thousands of 'knock-out lines' by using mice as a test object, when individual genes are switched off (knocked out) and become "silent genes"; the consequences of their "silence" can thus be studied.

 

The plant heterosis** laboratory headed by the author of the present article has developed transgenic plant forms with inserted foreign genes (human genes for the most part) controlling the synthesis of medical proteins (leukocyte interaction factors) and other structures having antigen characteristics and stimulating the production of antibodies. Such plants can work as producers of immunostimulating proteins or alternative vaccines.

 

In fact, the deciphering of the genomes of many species of organisms has produced a wealth of hitherto unknown evidentiary material - its volume soared dozens of times over; so analysis of this data flow called for new informational technologies and programs. Joining hands, Siberian biologists and mathematicians midwifed the birth of a new discipline, the bioinformation (biodocumentation) science. Alexei Liapunov, corresponding member of the national Academy of Sciences, and his following have made a crucial contribution to that (his school took body and form in Novosibirsk back in the 1960s). This line of research is being furthered at our ICG and other centers. Nikolai Kolchanov, RAS corresponding member, and coworkers have put forward a theory of gene networks, i.e. that of sequential implication of many genes in the realization of most different vital functions in the whole organism and in the cell alike. Pioneering investigations of these sophisticated processes are being carried on by other SB divisions as well.

 

Thus, the Institute of Chemical Biology and Fundamental Medicine has pioneered in methods of gene-targeted effects on pre-selected DNA sites (Acads. Dmitry Knorre and Valentin Vlasov, Doctor of Chemistry Nina Grineva).*** This is the world's only institution involved with systematic studies of the structure and functions of human ribosomes, the protein producers in cells. Dr. Galina Karpova (Chemistry) and colleagues have deciphered the structure of the key functional center of the human ribosome, where genetic information is decoded. They have discovered essential differences in ribosomal proteins.

 

 

* Noradrenaline - a neurohormone formed in the adrenal gland's medullar layer and in the nervous system, where it serves as a mediator (intermediary) of the nervous impulse passed via synapse (contact region). - Ed.

** Heterosis - the property of first-generation hybrids to surpass the best parental form in vitality, fertility and other characteristics. - Ed.

*** See: V. Vlasov et al., "Gene-Targeted Drugs", Science in Russia, No. 5, 2005. - Ed.

 

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A model of DNA protein interaction suggested at the Institute of Cytology and Genetics (ICG) of the Siberian Branch of the Russian Academy of Sciences.

 

This Institute is searching for new diagnostic systems and methods for obtaining medical preparations. Taking unorthodox RNA-cleaving catalysts they had created, researchers developed a viral RNA inactivation technique that does not impair the surface of viruses. Free of their harmful "filling", the thus inactivated viruses could go to make effective vaccines. As shown by experiments on animals, a new flu antiviral vaccine obtained this way is absolutely nontoxic and has a much more potent protective action than conventional analogs. This method is likewise applicable in obtaining vaccines against any RNA viruses - this is the research domain of Marina Zenkova, Doctor of Biology.

 

Siberian scientists are actively involved in major space exploration programs as well. Back in the 1970s and 1980s, a research team of Acads. Ivan Terskov, Iosif Hitelson and Dr. Heinrich Lisovsky (SB Institute of Biophysics, Krasnoyarsk) designed closed life-support systems for space crews on endurance flights. The name of their handiwork is BIOS, or biological system. Plant proteins were chosen as its essential component. However, because of financial straits this work had to be suspended in the 1990s. But given the interest of Russian and foreign scientists, this research work has been resumed on a more advanced basis.

 

Cosmic and terrestrial research areas are certainly interrelated, as seen in research carried out by a group headed by Andrei Degermendzhi, RAS corresponding member, at the SB Institute of Biophysics into aquatic microorganisms, and in a modeling of the carbon biospheric dynamics as a follow-up of processes taking place on land and in the ocean, including the rising amount of fuel combustion and contraction of forestlands. These models are highly important, related as they are to the aftereffects of human activity. If the negative action on nature is not checked, the current adverse trends in climate changes are bound to become irreversible as of the year 2050.

 

But back to terrestrial. The SB Institute of Physiology and Biochemistry of Plants (Irkutsk) has obtained important results on plant resistance to environmental factors, temperature above all. It has been demonstrated that the heat tolerance of plant cells largely depends on the structural and functional state of mitochondria (cell energizers), particularly their respiratory chain; these results have been obtained by RAS corresponding member Riurik Salyaev, and Drs of Biology Victor Voinikov and Yuri Konstantinov. The same research center has evolved transgenic tomato plants with insertions of hepatitis B and AIDS viruses possessing antigen characteristics and stimulating the formation of antibodies. In future such tomatoes could be consumed as edible vaccines against the two viral diseases (this work was carried out by RAS corresponding member Riurik Saliayev and Dr. Sergei Shchelkunov in cooperation with the State Research Center VECTOR*).

 

The range of SB research centers is truly wide indeed. It is all-important to keep a proper balance between basic science research in biology and the study of biore-sources over the vast expanses of Siberia. To tackle this dual task SB has set up an infrastructure of more than 20

 

 

* See: N. Krasnikov, "Siberian Vector" Science in Russia, No. 3, 2001. - Ed.

 

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comprehensive stations across Siberia for carrying out botanical, zoological, soil and forest observations over many years. Each year the SB presiding body endorses their activity programs, supports field parties financially, provides wherewithal for the maintenance of vivaria and botanical gardens; it is doing much towards equipment upgrading. Unfortunately our research centers are short of skilled personnel competent in handling up-to-date technology. For this purpose we have organized collective user pools of sophisticated gadgetry employed by workers of appropriate skills. Two pools like that are working at our Institute of Cytology and Genetics and at the Institute of Chemical Biology and Fundamental Medicine. One pool offers instruments for microscopic studies - modern light, fluorescence, electron and scanning (flying-spot) microscopes; the other provides hardware for genome sequencing.

 

Our biological institutes are active in applied research programs. For one, ICG has a record of about 40 patented and zonal strains and hybrids of plants. It has obtained new breeds of sheep, color breeds of foxes and minks. We have come up with an array of new medicinal preparations as well as effective and ecologically pure plant growth stimulants; and we have developed diagnostic systems, models of human pathologies and many other useful things. This list can be expanded by works done by other research institutes - soil maps, plant and animal kingdom atlases, forest utilization technologies, and so forth.

 

And yet our applied results are often not called for. Scientists are not to blame for that-the point is that we have no clear-cut pattern of product placement. That is why biological institutes have concentrated most of their effort on basic research. This is a correct strategy because major problem solving in what we have called challenges of the twenty-first century hinges on a sum total of knowledge on the evolution of living systems.

 

And now last but not least - the research personnel problem. Such personnel is coached mainly at Novosibirsk State University, and also at the Universities of Tomsk, Krasnoyarsk and Irkutsk, and at other senior colleges, too. This system of education works best at Novosibirsk, where education and science are integrated optimally. If you take our ICG, it is a base for departments of cytology and genetics, physiology and bioinformation science. Fourth-and fifth-year college students prepare their graduation papers at our laboratories. Thus we have a good chance of choosing the best for a graduate course. We hope they will carry on our work in committed involvement and bend every effort in protecting Siberia's huge biological resources with the aid of scientific know-how.


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