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The first virologists and medical virology in the USSR the 1930th.



ISSLEDOVANIYA

The first virologists and medical virology in the USSR the 1930th

E.S. Levina

Institute of history of natural sciences and equipment of S.I. Vavilov RAS, Moscow, Russia; e.s.levina@gmail.com

In article bright events of early history of virology in Russia, in particular the short period of existence of department ultrafiltuyushchikhsya viruses of Institute of microbiology of Academy of Sciences of the USSR and Central Virus Laboratory Narkomzdrava are discussed by RSFSR. Opening by L.A. Zilber of the phenomenon of symbiosis of a virus and a microbic cage and a discussion concerning the nature of this phenomenon are described during the All-Union virus meeting (1935); discussions on a problem of vaccination against flu between A. Smorodintsev and L. Zilber at meetings of Committee on flu of NKZ RSFSR (1936). The history of opening of the virus nature of the Far East tick-borne encephalitis (1937) connected with tragic events in lives of scientific community of medical microbiologists of the second half of the 1930th, their reflection in scientific literature and journalism and also a role of scientific works of medical virologists directed by key questions of fundamental biology in the second half of the 20th century is considered

The medical virology historically developed as the section of medical microbiology. By the beginning of the 1930th was known of viruses very little. Viruses were considered as infectious agents who pass through standard filters, the detaining bacteria (Berkfeld's candles and Shamberlen's candle), and do not breed in any other environment, except living cells of the susceptible owner. They were described as the certain "the filtered infectious beginning". By the end of the 1930th the sizes and forms of virus particles were already determined (Stanley, 1938; Elford, 1938). Believed that

© E.S. Levina

Utrudnim of the State Institute of National Health Care (SINHC) of NKZ RSFSR, 1926 lower row (from left to right): G.V. Vygodchikov, article laboratory assistant Pyzin; the first row (sit, from left to right): A.A. Zakharov, V.V. Frize, V.A. Barykin,

L.A. Zilber, L.M. Hatanever, A.A. Kompaneets; the second row (stand, from left to right): F.B. Kruk, P.V. Smirnov, M.P. Globkova, V.A. Chernokhvostov, O.V. Barykina, A.I. Goldin; the third row (stand, from left to right): (?), A.F. Kononova, E.N. Levkovich, (?), M.Yu. Grundfest, A.V. Beylingson, N. Utkina. top row: technicians of Microbiological institute Narkomzdrava (the photo from archive of family of Zilber-Kiselyov)

diameter of particles fluctuates from 10 to 300 millimicron and that the most part of viruses activators of an infection at animals — spherical shape, except for a virus of the poliomyelitis having the form of a thin stick.

In the 1930th in researches in the field of medical virology in the USSR two problems prevailed: flu and encephalitis. Work was concentrated mainly in scientific centers in the territory of RSFSR, more precisely in capital institutions — Moscow and Leningrad, and only in post-war time virologic scientific laboratories in Siberia and in the Far East were formed. Researches on flu should be developed in two equally important directions:

1) etiology and epidemiology of flu;
2) prevention and therapy of flu.

Researches on encephalitis were initiated by Narkomzdrav and the Defense Ministry in connection with the outbreak in the Far East of a disease of an unknown etiology and also included the called directions. In this case the task was complicated by need to find the vector of a disease pathogen as at the first approach to a problem (complex expedition of 1937) the inoculable nature of spread of an infection was revealed.

Among the scientists developing these problems, the largest figures were L.A. Zilber and A.A. Smorodintsev. The circle of specialists virologists in the 1930th was very narrow, and it is no wonder that Zilber and Smorodintsev's ways were repeatedly crossed. They were attracted in the same scientific councils and the commissions, they were opponents on problems of flu and encephalitis, pupils and Zilber's employees began the 1930th became Smorodintsev's employees in the late thirties — the 1940th. Their scientific activity, opening, polemic and opposition present the bright and sometimes drama history of formation to the USSR to medical virology.

General virology and flu

Opening in 1933 of the causative agent of epidemic flu (U. Smith, K. Andrews and P. Leydlow) quickly got a response in the Soviet laboratories. As, it agrees to the English data, the virus of flu could be allocated only on the African polecats, the lack of these animals did not give in the beginning the chance to develop work on studying a problem, so important for national health care, in the USSR. However by L.A. Zilber (Zilber, etc., 1937) it was shown that the flu virus, contrary to opinion of the English authors, can be allocated with direct infection myshey1, and this method was soon accepted by all laboratories. Later the susceptibility of rats to an influenzal virus was established, and scientists received one more laboratory animal for experimental studying flu and allocation of its activator. Activization of researches was caused by the flu epidemic which happened in 1936 in Leningrad, and even more large-scale, covered the large cities European part of the country, in 1940. In the Leningrad group of virologists and clinical physicians actively worked and still the young scientist proved as the capable organizer of researches A.A. Smorodintsev, then.

Anatoly Aleksandrovich Smorodintsev (1901 — 1986) graduated from medical faculty of the Tomsk university in 1923. Began scientific activity at the Tomsk bacteriological institute as the assistant, then underwent active service in RKKA as the regimental doctor of the Turkestan front where under the leadership of the parasitologist N.I. Latyshev and the infectiologist S.V. Viskovsky participated in protection of employees of bodies against mass diseases of tropical malaria. After demobilization it was sent to Leningrad for specialization in microbiology in department of comparative pathology of the Institute of Experimental Medicine (IEM) under the leadership of O.O. Gartokh. Here it conducted a number of researches in the field of medical bacteriology, namely in theoretical and applied disinfection: the course of streptococcal sepsis, pneumococcal lobar pneumonia and focal staphylococcal infections is studied. It for the first time proved existence

1 Tsit. according to the report of Central Virus Laboratory for 1936 Opubl.: Kiselyov, Levina, 2004, page 181.

the expressed correlations between weight of a clinical course of these diseases and quantitative tension of the microbic center in an organism of patients. Similar regularities were revealed by it in the course of the analysis of a batsillonositelstvo at a typhoid as in its short-term and asymptomatic "contact" forms, and at massive, long-term and steady forms of a typhoid in convalescents who were the main tank and a source of dispersion of bryushnotifozny infections (Tokarevich, 1981).

In 1933 A.A. Smorodintsev was appointed the head of department of bacteriology of the Leningrad scientific research institute of epidemiology and microbiology of Pasteur where was engaged in studying an etiology, pathogenesis and vaccinal prevention of flu. It and the staff of department, together with clinical physicians M.D. Tushinsky A.A. Korovin, on the basis of propaedeutic clinic of the 1st Leningrad medical institute during 1933 — 1936 carried out clinical laboratory observations on groups of volunteers.

Results of these and other observations were discussed at meetings of Committee on flu at the Academic Medical Council (AMC) of MZ RSFSR and members of this committee made a speech at a special session of UMS on flu which took place on November 14 — 17, 1936 2 At a session: V.A. Barykin, I.A. Dobreytser, L.A. Zilber and A.A. Smorodintsev and also L.I. Falkovich and E.V. Arhin, employees L.A. of Zilbera3.

Lev Aleksandrovich Zilber (1894 — 1966) these years was already mature scientist (Kisselev et al., 1992; Kiselyov, Levina, 2004). Being within 8 years a pupil and the employee of N.A. Barykin, the extreme supporter of the physical and chemical direction in immunology, he did not share the teacher's views on the nature of antibodies and developed own concept formulated by it for the first time in the report at the X Congress of bacteriologists, epidemiologists and health officers (1926), and is later in the monograph (Zilber, 1928). The statement of the author of rather proteinaceous nature of antibodies and antigens was supported further with his researches in the field of practical immunology — development so-called sugar antidenaturatsionny (HELL) vaktsin4.

In 1923 it for the first time received and described serological transformation of microorganisms on the example of vulgar a protea: proteas, placed in the kollodiye-vy sack isolating a microbe of Wednesday placed in an organism of a sypnotifozny guinea pig therefore vulgar proteas gained ability to react to antibodies to the causative agent of a typhus (Zilber, 1923). This opening preceded widely known work of F. Griffith in which practically the same reception, as at Zilber is used: the proof of transformation of one type of a pneumococcus in another under the influence of the ekstratsellyulyarny agent, in this case at joint introduction to mice of examples of live culture of one and the killed culture of other strain (Griffith, 1928). The chain of opening which foundation was laid by Zilber resulted in the following fundamental result — the transformation executed in 1944 the Urban district of Everi, K. Mac-Leoda and M. IAC Carti by means of pure DNA of one of pneumococci. It is known that the last experiment proved DNA role as material carrier of heredity (Avery et al., 1944).

To the middle of the 1930th Zilber gained experience of the epidemiologist, having headed group of specialists in elimination of outbreak of plague in Nagorno-Karabakh (1930) and smallpox — in Kazakhstan (1932), taught and conducted research, being professor and the head of the department of microbiology of the Central institute of improvement

2 State Archive of the Russian Federation (SARF). T. 8009. Op. 2. 71.
3 The structure of Committee see: GARF. T. 8009. Op. 2. 157. L. 117.
4 See primech. 1 at the end of article.

Lev Zilber (on the right) and Alexey Zakharov, 1934 (archive of family of Zilber-Kiselyov)

(CIU) of doctors in Moscow. In 1932 it became the deputy director of the Moscow bacteriological institute of I.I. Mechnikov where began works on virology.

In the center of its attention from now on and up to 1937.

It is impossible to call statement of this problem ordinary, however from the position taken in microbiology by Zilber in any way, it is quite explainable. First, at that time almost nothing was known of viruses, except the fact of their existence in the form of "the filtered infectious agent", and appears from Zilber's biography that from the very beginning of the scientific career he preferred to undertake the questions which are a little developed. Secondly, though it was also the step from bacteriology towards virology, in the center of attention and in this case there were microbes, viruses were rather tools, but not subjects of the analysis.

The essence of a task came down to whether it is possible to find one way or another interaction of microbes and viruses. Its statement was contrary to a top trend of world microbiology which sought to work with the pure cultures of the individual microbes introduced still by L. Pasteur and R. Koch. It was considered as a great achievement, and it was valid that. However the aspiration to work with pure cultures, at all advantages of such approach, completely excluded an opportunity to investigate intermicrobic and microbic and virus interactions which could not but be in living organisms.

In 1933 Zilber published article in which the question of a ratio of the "pure" and "mixed" cultures as a methodical basis of microbiological researches was sharply raised (Zilber, 1933).

Model which was used by Zilber — cultivation of an ospenny virus on yeast. Of course, Zilber understood that the probability of a meeting of the virus of smallpox affecting animals, and cages of the yeast which is usually not parasitizing on animals is extremely small if not to tell is insignificant. Therefore it was represented by model system, but not imitation of the situation which is found in the nature. The choice of yeast was connected with simplicity of their cultivation (technology of cultivation of animal cages in vitro at that time did not exist). Besides, a basic difference between eukariota and prokariota as well as between bacteria and viruses, it was not established and realized yet. As smallpox affects animals, i.e. eukariot, the barmy (eukariot-ny) model in this regard was adequate from an all-biological position and later time. As for a smallpox virus, at this time in the USSR worked only with three viruses of animals — smallpox, herpes and rage, therefore, the choice was small.

The group of the scientists involved with Zilber to this program from Bacteriological institute of NKZ USSR and the Central State Scientific Control Institute (CSSCI) of L.A. Tarasevich, subsequently the State control institute of medical biological medicines participated in researches. As barmy culture Torula kephir fungus was taken, and as virus — 8 strains of an ospovaktsina and 1 strain of human smallpox are tested.

After successful experiments of cultivation of smallpox on yeast the experiments were extended to viruses of herpes and rage.

Zilber's influence on the interest of researchers in studying viruses in their interaction with microbes can be tracked according to reports at the All-Union meeting on studying ultramicrobes and the filtered viruses which took place in December, 1935 in Moscow.

All-Union meeting

The meeting was organized under the auspices of Academy of Sciences of the USSR at the initiative of L.A. Zilber who interested with this idea of the director of Institute of microbiology of Academy of Sciences of the USSR, the large microbiologist, Georgy Adamovich Nadson (1867 — 1940). The institute grew from the microbiology of Academy of Sciences of the USSR created by G.A. Nadson Laboratorii in Leningrad where Georgy Adamovich worked at the same time at the State radiological and radiological institute and where influence of X-rays on variability and heredity of yeast and mold mushrooms was for the first time established to them (Nadson, Filippov, 1925). In 1934 the Academy of Sciences of the USSR was transferred to Moscow, the Microbiological laboratory received the status of institute and an opportunity to be located indoors on Big Kaluga ulitse5 together with other institutions of the academic Bioassociation.

The documents which remained in RAS Archive demonstrate that the most part of loading on the organization of a meeting in the House of congresses and conferences of Academy of Sciences of the USSR laid down on L.A. Zilber. As the vice-chairman of the organizing committee, the member of program committee, he corresponds on all questions (financing of a conference, the invitation of participants, the organization of places in hotel and hostels, food of participants, the publication of theses and works of a conference). In addition, he makes at the first meeting the program report, after an opening speech

5 Nowadays Leninsky Ave., 33.

G.A. Nadsona and a ritual greeting of the audience to the government and companion Stalin (on December 14), and with the second report devoted to the symbiotic phenomena at viral infections (on December 16). It prepared article for the Pravda newspaper about the meeting course.

The experts who are already working with viruses of animals and plants gathered for the first time.

The list of participants and a subject of reports are extremely interesting. Not only medical and veterinary specialties, from the staff of bacteriological institutes and the stations to the elder of domestic microbiologists and immunologists of the honorary academician N.F. Gamaley, professorate of Medical genetic institute and Military scientific and medical institute of RKKA are presented. Reports are made by physiologists and geneticists of plants, such famous scientists as N.I. Vavilov, Doncho Kostov, V.L. Ryzhkov. Narkomat's guide of agriculture and Narkomat of health care is invited. The organizing committee assumed the invitation and foreign scientists, but the sanction for mailing of invitations was not received in view of limitation of means (in 1935 in Moscow and Leningrad the International physiological congress was already carried out). Reports and in a debate were made by a lot of youth, subsequently taken the noticeable place in medical virology and microbiology: E.N. Levkovich, A.K. Shubladze, A.D. Sheboldayeva, V.D. Timakov, N.A. Zeytlenok, etc.

The first report of Zilber represented the review of a condition of works on virology in the world and contained recommendations to the organization of researches in this area in the USSR:

"... Studying the filtered viruses achieved in recent years enormous success, there were resolute shifts in development of a number of the most difficult problems. Unfortunately, we lag behind this rapid growth, work on studying the filtered viruses is still insufficiently developed in our country.

An insistent task which, first of all, has to be considered by the real conference is need of elimination of this lag and broad expansion of study at us the filtered viruses. On this business considerable funds will be required. But it is hardly possible to doubt that they will pay off in the next time. As studying the filtered viruses demands very expensive and special equipment and as shots of experts in this area at us are not numerous, the organization of this work in our country on the following scheme is represented to me the most expedient. The academy of Sciences has to be the center of theoretical work in this area and study mainly biology of the filtered viruses. For this purpose it has to have a necessary complex of laboratories. At the same time Narkomzdrav, People's Commissariat for Agriculture represented by Veterinary management and Academy of agricultural sciences of V.I. Lenin have to create the virus laboratories devoted to special studying viruses of the person, animals and plants. This division should not have formal character because in a number of cases quite expediently parallel study, both viruses of animals, and viruses of the person.

Along with it virus work at microbiological and veterinary institutes has to be strengthened.

The close attention needs to be paid to training. It is necessary to ask Narkomzdrav to organize through the Central institute of improvement of doctors long-term courses for training of specialists on the filtered viruses which along with the general theoretical preparation in this area would give also special preparation on viruses of the person, animals and plants. It is necessary to send abroad to virus institutes of experts for acquaintance with methods of studying the filtered viruses" (Zilber, 1937, and 15).

The report "The symbiotic phenomena at viral infections" in which the thought developed that the possibility of symbiosis of viruses and microbes is an independent and important problem both from the all-biological point of view, and from a position of medical microbiology, caused a heated debate.

Generalizing experimental data, L.A. Zilber suggested about the possible, in his opinion, mechanism of interaction of a virus and a microbic cage in the conditions of joint cultivation:

"We know that the virus is an obligate parasite of living cell, we know that the virus throughout the millennia meets in any infections when it gets into an animal and vegetable organism, it gets into airways, and into a pharynx, etc. where it meets flora which covers these gate. Whether this meeting which takes place of the millennium can be indifferent? It is illogical to assume that the virus, developing devices for life only in living cell, cannot at the same time develop also ability to reproduction on that cage which it meets the millennia. I do not know any biological law and any biological theory which would speak against such assumption. Therefore it is possible to think that the virus, being absorbed on a cage, on this cage and breeds. But it is possible to assume also another. Perhaps, the virus will not be absorbed on a cage at all, and will get into a cage, and having got into a cage, can remain or not remain in it. Farther a virus, having got into a cage, can breed in a cage, and such opportunity cannot be excluded. At last, also other forms at which the virus, remaining in the environment, nevertheless, in the environment will breed, stimulated in this regard by a microbe as it is represented on the scheme are possible... And at last, the virus with a microbe with the antagonism phenomenon is possible in such combination. The question of antagonism of a virus and a microbe is not lifted in literature at all. Existence of a microbe can be adverse for a virus, on the other hand — presence of a virus can be adverse for a microbe" (Zilber, 1937, page 219).

Having mentioned the works in which results of selection of separate colonies of the yeast containing a virus are given, the speaker shows that it is possible to increase sharply virulence of cultures and to bring it to a limit. He emphasizes this fact as the proof that

"... the virus in yeast, undoubtedly, is transferred by the most barmy cage, but not Wednesday in which there is a growth of barmy culture. & lt;...> At last it is established that these cultures contrary to all that we know, can remain at the room temperature, keep the virulence.

& lt;...> These features of culture & lt;...> demonstrated that viruses in these cultures undergo biological changes, and it, of course, and it was necessary to expect because it is difficult to think that the filtered virus, one of characteristic properties of which is ability to light variability which acts even when we intertwine a virus from one susceptible animal to another — a dog and a rabbit, the person — it would be difficult to think that the virus, entering the symbiosis phenomenon with a microbe, will not change" (Zilber, Vostrukhova, 1933, 1934; Zilber, Wostruchowa, 1933; Zilber, Timakov, 1934). "Our works were checked and also lt are now checked by a large number issledovateley6.;...> The Phenomenon about which we speak was called by us an allobioforiya — carriage of other life. It seemed to us that we have the right to enter this name because hardly someone can deny that this phenomenon is, undoubtedly, a peculiar form of symbiosis, a symbiosis form which was not in the field of attention of researchers, a symbiosis form which has certain specifics, and, owing to this fact, this

6 Ospenny cultures were transferred to CGNKI, CIEM, Mechnikovsky institute in Kharkiv (see: Zilber, 1937, page 222).

the form has the right for the independent name. It seems to me that even impartial observers who do not agree with us on those theoretical prerequisites from which these observations grew cannot deny nevertheless that the fact that in these numerous experiments the carriage virus microbes takes place. How differently it is possible to explain these phenomena?

& lt;...> It is necessary to tell several words and about whether the carriage of viruses is microbes the main form of their existence.

Barykin specifies that viruses as it was for the first time proved by us, change in microbic cages, and that therefore if the allobioforiya would take place under natural conditions, viruses in general would have to degenerate. It is possible that viruses really would have to change if their reproduction on microbes was the only form of their existence on Earth. But nobody and anywhere, as far as I know, insists on it, and is unclear why Barykin raised this question. & lt;...> In a number of the works devoted to an allobioforiya the change of immunogene properties of cultures which in certain cases, for example at a typhus, occurs pretty fast, already in the first generation is noted. Undoubtedly, this fact takes place concerning some cultures of the filtered viruses. However there are a lot more ambiguities. The fact is that along with the facts which speak about easing of immunogene ability of cultures there are experiments speaking about them activity very big in this regard. whether

alloforny cultures Have any practical value?

I still avoided to comment on it because for me is absolutely clear that the new biological phenomenon has to be comprehensively studied before it is able to receive practical use and that not any biological phenomenon in general can be used practically. However now there are works in which authors point to a possibility of practical use of alloforny cultures" 7.

Considering that experiments on an allobioforiya were conducted in different laboratories by different researchers with different viruses, various cultures of microorganisms owners, it seems extremely improbable that their results were in all cases artifacts.

In the Zilbera laboratory the strain of a virus of smallpox existed in allobioforny culture with a kefiric fungus more than 13 years and died in 1941 when Zilber was in the conclusion, and the situation in Moscow did not dispose to classes the science distracted from defensive tasks.

In 1956, having returned to interpretation of the experiments executed in 20 years before Zilber discussed three opportunities which theoretically could be implemented in allobio-forny cultures (absorption of viruses on microorganisms; carriage of a virus microbes; reproduction of a virus in microbic cages). He considers all listed forms of interaction of viruses and microorganisms as different forms of manifestation of symbiosis between them and considers that the most frequent form is the viroforiya (carriage of viruses microbes) though he at the same time gives numerous cases of absorption of viruses on different microbic cages. Here it introduced the interesting idea that the bakteriofagiya evolutionarily could arise from a viroforiya (Zilber, 1956).

In January, 1936, after a successful completion of a meeting, the administration resolved issues of the organization of two centers of virologic researches — the Central Virus Laboratory (CVL) Narkomzdrava of RSFSR and department of the filtered viruses of the Institute of microbiology of Academy of Sciences of the USSR consisting of two sections — viruses of animals and viruses of plants. The fate of these first specialized virologic laboratories and their research teams was defined by the events far from the world of science, and in 1937 — 1938 was solved directly by the country leaders.

7 Cm primech. 2.

NKZ RSFSR central virus laboratory

CVL was organized on the basis of Bacteriological institute of I.I. Mechnikov according to the order Narkomzdrava. Reporting to the people's commissar P.G. Sergiyev about results of work of Laboratorii for the first year of its existence, the director L.A. Zilber notes inevitable difficulties of organizational character ("work could be developed only in the second quarter 1936 in the absence of own room and the equipment; a part of scientific personnel is forcedly accepted on a half of a rate and combines work in other scientific institutions") and emphasizes one of important results of work of the first year — staff recruitment. From 15 scientists of Laboratory 12 have special preparation on viral infections, 2 of them have degree of the doctor and 7 — degree of the candidate medical nauk8. Presence, also obligatory those years, in the state "three Party members and one sympathizer" is noted. The scientific program planned under three sections is executed: studying the mechanism of antiviral immunity (to viruses herpes encephalitis and an infectious ektromeliya, a pilot study); an etiology of epidemic flu (strains of a virus of the Moscow flash of 1936 are allocated, comprehensive study and comparison with the English strains is carried out them); studying biological properties of the causative agent of a typhus (the new faultless method of diagnosis of an experimental typhus is developed) and experimental measles (are in the current year not finished and will be continued in the following) 9. The relevance of the put problems and a combination in their development of fundamental and practical tasks is obvious. On the mechanism of antiviral immunity it is established that leukocytes do not destroy the studied viruses in an organism of immune animals: the immune organism gets rid of viruses not by their destruction as it takes place with bacteria, and by their allocation through kidneys. The result has not only theoretical value, but also explains difficulty in receiving antiviral serums on large animals: at immunization, for example, a virus of encephalitis of a horse an enormous part of a virus as a result, according to the author, "gets to a stall", but not to an animal organism (see: Zilber, etc., 1937a, page 53).

As for data on flu, we will remind that the epidemic flashes of the Spaniard which swept across Europe and reached Russia in the 1920th extended freely since the medicine did not develop specific treatment of viral flu yet. In CVL as it is noted above, were not only infectious strains are allocated, but also the possibility of allocation of strains from the person is experimentally proved by direct infection not of polecats which cultivation is in vitro accompanied by great difficulties, and mice that significantly facilitated receiving strains. It allowed to develop the same year enough a virus, to carry out vaccination of volunteers, to establish its full harmlessness and to specify a technique and also to study influence on a virus of flu of various chemical agents.

These works which were continuation of researches which were conducted by Zilbe-rom and his colleagues since 1932 at department of microbiology of the Central institute of improvement of doctors and in TsGNKI laboratory of L.A. Tarasevich were crossed on subject with A.A. Smorodintsev's works 1933 — 1937 in department of bacteriology of the Leningrad institute of epidemiology and microbiology of Pasteur.

8 Award of academic degrees was entered into practice by the solution of SNK USSR in 1934
9 Archive of family of Zilber-Kiselyov. Published: L.L. Kiselyov, Levina E.S. Lev Aleksandrovich Zilber. M.: Science, 2004. Page 181-182.

In the draft of the staff list of CVL offered by the director six departments from which three scientific (morfobiologichesky, immunological and department of malignant tumors), three auxiliary (photographic and histologic offices and a vivarium) appear. The offer of department of malignant tumors is essential: Zilber admitted one of performances of 1935 that in 1934 he was already ready to be engaged in viruses with which connect the malignant growth of cages and fabrics. About same L.A. Zilber's letter which remained in personal archive of L.L. Kiselyov to E.N. Levkovich, at that time to the employee of CVL testifies:

"Elizabeth Nikolaevna Mnogouvazhayemaya!

I will return to Moscow near on September 5. Apparently, you will return not earlier, write to me: Crimea, Koreiz, sanatorium of KSU "Gaspra". I will write to you then from where to receive a strain of tumors.

Look at work of Lochart&a in Brit .Med. Journ. No. 3877, 1/3 April, 1935, there the report of views on a zlok. tumors and in Pr. Medical 8/V No. 37 too 1935

In my plans and in general, and concerning you nothing changed (it is very difficult to force them to change me). On the contrary, everything very much favors to my undertakings in this area. NKZ gave me 40 thousand on the last quarter for virologic work. From Leningrad comes to me (illegibly), it is already approved by my deputy. And all prospects are very favorable.

I am very glad that you have well a rest and recover. It will be necessary to organize so in Moscow work that all this did not come to naught, and on the contrary — would be fixed. I think that it, certainly, is possible.

Accept my warm hi,

L. Zilber".

The report of views on malignant tumors is mentioned in the letter not accidentally: this problem will become the main scientific interest of Zilber in post-war years and will remain to that until the end of his life.

In February, 1937 in connection with the CVL expansion there are several offices, one of which — department of neurotropny viruses — is headed by Elizabeth Nikolaevna Levkovich (1900 — 1982). It is the country's first organizational structure which is purposefully engaged in neurotropny viruses.

E.N. Levkovich, 1940 (archive of family of Zilber-Kiselyov)

Institute of Pasteur of the Discussion on a problem of vaccination against flu

The problem of pathology, pathogenesis and prevention of flu since 1934 was in the center of scientific interests of department of bacteriology of Institute of Pasteur. Here the main attention was paid to clinical trials, in particular comparative studying clinical reactions to introduction to volunteers of laboratory strains of a stick of Pfeyffer or a virus of the flu, virulent for polecats, subjected long

attenuation in passages on white mice. Researches were put and conducted in spite of the fact that an etiologic role of a stick Pfeyffera was considerably shaken by materials of bacteriological and serological inspections of patients in the period of the "Spanish" flu 1918 — 19

Authors of these works, however, remind that in 1931 the research in which the combined participation of a pnevmotropny virus and a gemoglobinofilny stick of pigs in an etiology of influenzal pneumonia of pigs, on clinical and experimental properties exclusively close to flu of the person was established was published. R. Shoup in this respect stated a hypothesis according to which an epizooty of pneumonia at pigs in 1918 — 19 arose owing to infection of animals with the Spaniards virus of the person. Further this virus was preserved in herds of pigs in the state low-changed over time of which the anti-gene structures close to the option of the "Spanish" virus of the person which is not allocated and definitely not identified, but continuing to remain in population of people were characteristic. This hypothesis received in the early thirties wide rasprostraneniye10.

In the conditions of clinic the volunteers (medical students of the Leningrad higher education institutions groups on 15 people) were observed within 14 days of September — December, 1935 after inhalation of aerosol of culture of a stick of Pfeyffer. Detailed inspection by therapists (M.D. Tushinsky, A.A. Korovin), otolaryngologists (Ya.A. Gottlieb) and also bacteriological and serological researches of patients were conducted. In February — April, 1936 according to the same scheme the survey of the patients who received aerosol introduction flu virus medicines was carried out (a strain Leningrad, is allocated with cultivation on polecats during a flu epidemic in January, 1936 and is adapted in the course of long passages to lungs of white mice that considerably weakened this virus for people). Results of this kliniko-experimental work as Smorodintsev wrote, "had significant effect on fast recognition of a pnevmotropny virus the true causative agent of flu at people and its further use for active immunization against flu" (Smorodintsev, 1981, page 30). Besides, it prepared the popular brochure about flu for health education of the population (Smorodintsev, 1939).

In 1938 A.A. Smorodintsev participated in the second Far East expedition, in 1939 — went to the third Far East expedition. The first Far East expedition (1937) L.A. Zilber, soon after its end ran the People's Commissariat for Internal Affairs arrested by bodies. The events which came during the period from return of Zilber and colleagues from Khabarovsk in August, 1937 and before its release from prison in June, 1939 will be considered below. Here we will return to a flu problem in which study both virologists continued to be engaged, despite their interest in studying the causative agent of tick-borne encephalitis — a neurotropny virus. The open discussion of two specialists in a problem of vaccination against flu took place after World War II, during the All-Union conference on flu in the spring of 1946 11, but data of researches of the 1930th

In the report Zilber were a basis of a discussion states the approach to creation of the vaccine against flu in the need in which country is very high. It, as well as all experts, oz

Grande Gabriela Agnese
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