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Microbiology opened its secrets to him

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Vladimir Dmitrievich Timakov, whose birth centennial we marked in 2005, is among the galaxy of foremost scientists of the 20th century. As a director of the N.F. Gamalieya Research Institute of Epidemiology and Microbiology, full member of the USSR Academies of Sciences and Medicine, and President of the Academy of Medical Sciences, Dr. Timakov has made a remarkable contribution to theoretical medicine, applied epidemiology and immunology, and other disciplines. Acad. Timakov has performed well as science and public health organizer, too.

Vladimir Dmitrievich Timakov was born on July 22, 1905. Upon graduation from middle school, the youth left for Siberia where he got enrolled in the Department of Medicine of Tomsk University. His teachers were eminent scientists of the day, such as I. Losifov (anatomist), A. Timofeyevsky (author of in vitro cultivation of organic tissues), M. Kurlov. As a bright student Vladimir Timakov was recommended for a postgraduate course at the Department of Microbiology headed by Prof. P. Butyagin, a medical doctor who founded the Siberian school of bacteriology and microbiology, and organized the Tomsk Institute of Bacteriology. Under his tutorship Timakov carried out his first research works.

In 1929 Vladimir Timakov became a certified general practitioner. He made laboratory experiments, surveyed outbreaks of typhoid fever and sanitary conditions in the locality, and looked into the causes of epidemics.

In 1934 the young medical doctor was invited to take a job at the Turkmen Institute of Microbiology and Epidemiology, where he headed a department in charge of vaccine and serum output. He focused attention on combating such grave infectious diseases as dysentery, typhoid and typhus, smallpox and rabies. Proceeding from the data he obtained from many experiments on animals and vaccinations of the local population, Dr. Timakov saw it was necessary to upgrade preventive medication for intestinal infections. His fresh, innovative approach saved good health of thousands and thousands. Meanwhile in 1936 the young researcher defended his Cand. Sc. thesis on the antigen, immunogen and reaction characteristics of AD and ordinary heat-treated vaccines. His work on immunity had gained renown by that time. Under the supervision of Dr. V. Suknev, heading Tomsk University’s Department of Microbiology and Epidemiology, V. Timakov studied filterable forms of bacteria, concentrating thereby on the immunogenetic action of inactivated (dead) vaccines. The incidence of intestinal infections was still high at the time, while prophylactic remedies were but of little effect. V. Timakov summed up his research findings in a doctoral dissertation dealing with lactic typhoid and paratyphoid vaccines (1941).

Later in the 1930s and early 1950s V. Timakov zeroed in on problems related to the heredity and variability of microorganisms. His laboratory was one of the first in this country to undertake versatile studies of bacteriophages – the viruses proliferating within bacterial cells and destroying them. These are high-specificity microorganisms: for instance, dysentery phages attach only to analogous (dysenteric) bacteria so as to inject their hereditary material. Typhoid phages cannot infect choleric vibrions, while these do no harm to dysenteric pathogens. And so on down the line. As Timakov and his team found out, it was possible to identify bacterial infection by the presence of corresponding phages in body secretions, in foodstuffs and in drinking water, too. A new phage diagnostic method, the reaction of successive growth of the titer of the specific phage, was thus evolved.

In time Timakov and his coworkers moved into a qualitatively new, molecular level of research. For example, phage DNA can be inoculated into a bacterium in vitro in a procedure that does not occur under natural conditions. More than that, such artificial contamination sparks proliferations of heterologous (foreign) bacteriophages. Such experiments carried out by Vladimir Timakov and Professor Boris Ilyashenko heralded a gene engineering age.

There was something else to attract interest: small fragments of DNA discovered in bacteria; though not bound to the chromosome as a rule, these fragments carry genes responsible for many properties of the bacterial cell. Such genetic elements, the plasmids, are endowed with intriguing characteristics: additional to and independent of the cell chromosome and dispensable to the cell, they are capable of autonomous replication. That is plasmids can be a source of additional genetic information. Dr. Timakov, conscious of the future pathways of science, set up a laboratory involved with plasmid molecular genetics. Discovery of mechanisms underlying the mutual interaction of plasmids and their effect on bacterial cells could help unravel the secret of drug resistance of microorganisms.

V. Timakov has made a major contribution in the identification of mechanisms responsible for the pathogenic action of bacteria, i.e. heir ability to infect the organism. Jointly with his pupil, Prof. Valentina Petrovskaya, Dr. Timakov determined the causes of Pathogenicity of intestinal bacteria. the results of these studies are summarized in their book Biology and Genetics of Flexner Shigellae (1972).

Vladimir Timakov was one of the pioneers in studying microorganisms devoid of a thick cell wall and in elucidating their role in relapsing (recurring) infections; he is the author of the theory on mycoplasmas and L-forms of bacteria. Individual bacterial cells, not killed by medical drugs, lose the larger part of their cell wall and take on the spheroid form. They kind of get underground, become latent, and are hard to detect with the use of regular diagnostics. In their new guise L-bacterial forms are still capable of inducing pathogenic processes, albeit in a modified form.

The point is that L-forms of different bacteria endure for a long time and become causative agents of prolonged chronic diseases (meningitis, rheumatism, urogenital infections, etc.), which are more difficult to cure than those caused by bacteria having a thick cell well. As to mycoplasmas, these are a separate class of microorganisms likewise capable of infecting the organism. V. Timakov was closely involved with studying both pathogenic mycoplasmas and L-forms of bacteria and developing laboratory diagnostic methods.

In the late 1960s V. Timakov set up a task research team that was to study the latent forms of infections. It was a big mystery: where and how an influenza virus survived in between epidemics? Perhaps within the lost organism? Devising a target-oriented method, Timakov and his pupils isolated an active influenza virus from flu-infected mice a month, three and six months after the bout. More than that, the host murine females with a long history of virus carriage passed down the virulence to offspring. Young mice born to them developed bad aftereffects in the form of bad lesions of organs and tissues.

Vladimir Timakov devoted more than 40 years to teaching. The subject-matter of his lectures and practicals is condensed in the manual Microbiology (1973), still thought to be one of the best by virtue of its high theoretical level. He pioneered in organizing tuition courses on molecular genetics and molecular biology of microorganisms. Vladimir Timakov was one of the men who organized this country’s first medico biological department at the N.I. Pirogov Second Medical College in Moscow now graduating medical doctors with a good background in biophysics, biochemistry and biocybernetics.

For many years V. Timakov was board chairman of the national Society of Microbiologists, Epidemiologists and Infectionists: he was Deputy Editor-in-Chief of the editorial board of the Great Medical Encyclopedia and editorial board member at many specialist journals here and abroad.

“The main thing for man of science is to be useful to people, to see the fidelity of his findings and be sure that he is on the right track.” That was his motto both as scientist and citizen, and he abided by it all through his life.

 


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