Onproliferation

References
T.A Abolina and V.N. Savelyev, “Study of  the virulence of  cholera vibrio isolated in Azerbaijan SSR” 
(in Russian), in: Aktualnye voprosy epidem., profil. i diagn. OOI. Tez. dokl. nauch. konf. (Abstracts of  Reports 
to the Scientific Conference: Current Issues in Epidemiology, Prevention, and Diagnosis of  High Risk Infections), 
Stavropol, 1989, pt. 1, pp. 3-4.
A.F. Bryukhanov, “Molecular-biological characterization of  El Tor cholera vibrio strains of  various 
origins” (in Russian), Author’s abstract of  candidate dissertation, Saratov, 1991.
N.F. Bystry, et al., “Method of  differentiating virulent and avirulent vibrios using specific virulent 
bacteriophages” (in Russian), Problemy OOI, 1970, no. 1, p. 123.
G.M. Grizhebovsky, Cholera in the Caucasus (in Russian), Doctoral dissertation, Stavropol, 1997.
B.A. Kiyakhtanov, L.F. Zykin, R.T. Gerasimenko, et al., “Cholerigenicity of  El Tor vibrios” (in Russian), 
Zdravookhr. Turkmenistana, 1977, no. 9, pp. 12-16.
E.A.  Mosktivina,  “Scientific  basis  for  the  principles  of   improving  cholera  control  measures”  (in 
Russian), Author’s abstract of  candidate dissertation, Saratov, 1996.
V.P. Sergiev (editor), Epidemiologichesky nadzor za kholeroy v SSSR (Epidemiological Surveillance of  Cholera in 
the USSR), Moscow, 1989.
V.I. Svyatoy, V.M. Razvykh, and V.A. Friauf, “Distinguishing features of  the ecology of  El Tor vibrios 
circulating in Turkmen SSR” (in Russian), Zdravookhr. Turkmenistana, 1991, no. 1, pp. 30-33.
V.I.  Svyatoy,  R.T.  Gerasimenko,  and  V.M.  Razvykh,  “Results  of   a  controlled  field  epidemiological 
experiment to determine the epidemicity of  hemolysis-positive El Tor cholera vibrios” (in Russian), 
Zdravookhr. Turkmenistana, 1991, no. 2, pp. 35-38.
V.P. Vlasov, and Ye.V. Monakhov, “Prospects for molecular-biological approaches to studying cholera” 

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(in Russian), Abstracts of  reports to the All-Union Conference on Cholera, Rostov, 1988, p. 44.
L.F. Zykin, B.A. Kiyatkhanov, and R.T. Gerasimenko,  “El Tor vibrios of  various enteropathogenicities” 
(in Russian), Zhurnal mikrobiologii, 1978, no. 3, pp. 115-19.
L.F. Zykin, V.I. Svyatoy, and R.S. Zotova, “Study of  enteropathogenic hemolytic El Tor vibrios” (in 
Russian), Zhurnal mikrobiologii, 1978, no. 2, pp. 118-19.
L.F. Zykin, and A.T. Yakovlev, Ocherki po laboratornoy diagnostike opasnykh infektsiy (Briefs on the Laboratory 
Diagnosis of  Dangerous Infections), Saratov, Izd. SGU, 1993, pp. 75-82.
Editor’s Note
M.I. Levi (p. 225)
This note discusses considerations for publishing “How it really was” by L.F. Zykin (pp. 217-225). It also discusses 
the emotions raised by questions of  priority of  scientific discoveries.
Full translation:
The  Interesting Stories… are not subject to censorship by the editor. The authors are solely 
responsible for their content. Authors must understand the responsibility they are undertaking. 
However, none of  this excludes the possibility that different authors will express different 
opinions about a particular phenomenon or a particular person.
Problems of  priority rather often carry a heavy emotional load that makes them the subject 
of  various claims and analyses. One of  these conflicts is described by L.F. Zykin in his article, 
“How It Really Was.”
In a number of  cases, some of  the active authors for our series have had the opportunity to 
read through manuscripts before publication. In the present case, researchers who took part 
in studying cholera in our country were given the opportunity to read the article by L.F. Zykin. 
As a result, the editor received responses that we publish below. Readers should note that we 
did not feel we had the right to refuse to publish L.F. Skin’s article or change its content, but 
we recognize that it would be reasonable to present other opinions.
What Do You Mean ‘How It Really Was’
R.S. Zotova (pp. 226-29)
Commentary on the article “How it really was” by L.F. Zykin (pp. 217-25).

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Full translation:
L.F. Zykin mentioned my name in his reminiscences. In fact, I worked at the Turkmen AP 
Station for a long time and was a direct participant in several of  the events described.
In 1965, when cholera outbreaks occurred in Iran, Afghanistan, Uzbekistan, and elsewhere, 
extensive cholera prevention measures were taken in Turkmenia because the republic borders 
all these countries. At the time, I was working in the Kizil-Atrek (Gyzyletrek) district along 
the Iranian border. The Atrek (Etrek) River flows through this district and is the main water 
source for most of  the district’s population. Every evening, we heard Turkmen-speaking 
medical workers from Iran urging residents of  Turkmenistan to wash vegetables and fruits in 
potassium permanganate solution, not to drink untreated water, and so on.
In two months of  work, we isolated from Atrek River water about 50 strains of  Heiberg 
group one vibrios agglutinating with O-cholera serum in diagnostic titers. At that time, similar 
cultures were isolated from nearly all the water bodies in the republic.
Around November or December, N.V. Uryupina, senior scientist at Mikrob, brought us 
Mukherjee phages. She familiarized us with what were then new methods (identification tests, 
differential  tests,  etc.).  Working  with  her  we  identified  strains  isolated  from  the  towns  of  
Kushka [Serhetabat] and Kizil-Atrek. This work identified the strains as El Tor vibrios, most 
of  which were Ogawa serotype, some were Inaba.
The director of  the Turkmen AP Station at that time was Mariya Mikhaylovna Tikhomirova. 
She asked me to develop the results into a candidate dissertation. I took the data to Mikrob. 
Yevgeniya Ilinichna Korobkova agreed to direct my dissertation work. This took place at the end 
of  the year, and the topics for the new year had already been approved. Boris Konstantinovich 
Fenyuk, deputy scientific director of  Mikrob, convened the Academic Council, which approved 
my dissertation topic. In addition, Boris Fenyuk helped me learn new methods, including 
luminescence microscopy. I write about this in detail because I wanted to gratefully remember 
Mariya Tikhomirova, Yevgeniya Korobkova, and Boris Fenyuk, who lived, worked, trained 
students, and contributed very much to the study of  high-risk infections, mainly the plague 
pathogen.
I defended my dissertation in 1969. During that entire time, there were no epidemics in 
Turkmenistan, but El Tor vibrios continued to be isolated from the environment (waters, 
wastewaters,  fish,  and  frogs).  There  was  an  urgent  need  to  determine  the  virulence  of   the 
strains. V.I. Svyatoy was assigned to study this problem and L.F. Zykin agreed to direct his 
work.
I.V. Isupov, D.L. Shmerkevich, N.S. Goncharova, and other scientists at Mikrob also studied 
the virulence of  El Tor vibrios isolated from the environment in Turkmenia. In one instance, 

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the scientists observed a restoration of  the cholerigenic properties of  weakly virulent strains 
of  El Tor vibrios by passing them through the small intestine of  nursling rabbits.
This work was duplicated by a commission based at the Turkmen AP Station. There were 
different opinions about the cholerigenicity syndrome of  the dead rabbit. In my view, the 
syndrome was positive, but other people thought it was negative. The dead rabbit’s small 
intestine, which was swollen with clear liquid, contained several very small green lumps. This 
caused the dispute about the cholerigenicity syndrome.
It should be noted that at the same time as V.I. Svyatoy’s work, other work was being done in 
the AP Station laboratory to study whether El Tor vibrios isolated from various environmental 
features in Turkmenia were capable of  producing choleragen exotoxin in vitro (using the 
terminology of  that time). This work was done by Elvira Zhukova, a graduate student at 
the N.F. Gamaleya Institute, and was directed by I.A. Shaginyan, director of  the Genetics 
Laboratory at that same institute.
In the first stage of  this work, Zhukova found that the “Turkmen” strains were differentiated 
by the following characteristic; El Tor vibrios isolated from patients produced large 
amounts of  toxin, while those isolated from the environment produced little toxin or 
were atoxigenic vibrios.
At present, as Zykin already noted, the virulence of  El Tor vibrios is evaluated based on the 
potential ability to produce cholera toxin (Vct+) or the absence of  this ability (Vct–). L.S. 
Podosinnikova, who wrote a doctoral dissertation on El Tor vibrios isolated from various areas 
of  the former Soviet Union, also noted a difference in strains based on the presence or absence 
of  the gene responsible for the synthesis of  cholera toxin (Vct+ or Vct–). I do not know what 
became of  the work done by Svyatoy or Zhukova, because soon afterward I left Turkmenia 
and never did any more work with vibrios. But why did Zykin not mention Zhukova’s work in 
his article? After all, this was unique work for those times.
From Zykin’s article, I learned that Svyatoy did not defend his dissertation, and the author 
blamed D.L. Shmerkevich and N.S. Goncharova. The Academic Council makes the decision 
about the defense of  a dissertation, and they were never members of  the Academic Council of  
Mikrob Institute. Incidentally, Goncharova died of  cancer, as did Svyatoy.
Now, about the reversing of  cholerigenic properties of  cholera vibrios: again, Podosinnikova 
showed that in two cases out of  four, a stable reversal of  cholerigenic properties of  weakly 
virulent Vct+ strains of  El Tor vibrios was obtained by passage through the intestine of  
experimentally infected nursling rabbits.
As for the philosophical statement of  film director Eizenshtein, the only people who can answer 
that are personnel at the Turkmen AP Station who continue to live and work in Turkmenia. 

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After all, over 20 years have passed since the events described by Zykin. During that time, they 
could have analyzed the epidemiological situation and determined whether the strains did or 
did not have the Vct gene.
In this regard, I can again quote Podosinnikova: “In a number of  areas (Uzbekistan, 
Turkmenistan, Rostov, Astrakhan, Donetsk, and other regions), repeated cholera outbreaks 
were recorded against a background of  a long period of  isolating El Tor vibrios from the 
environment.”
So what do you mean, “How It Really Was”?
R.S. Zotova
P.S. On January 14, 1998, I called I.A. Shaginyan and asked what had become of  Zhukova. 
He said that Elvira successfully defended her candidate dissertation and continued to work at 
Turkmen Institute of  Epidemiology and Microbiology (TIEM). At one time, she was deputy 
scientific  director  there.  In  her  dissertation,  Zhukova  concluded  that  some  El  Tor  vibrios 
circulating in the environment of  Turkmenia did not produce exotoxin (choleragen), while 
others produced it to varying degrees.
Dear Yury Grigorevich
Yu.M. Lomov (pp. 229-31)
Commentary on the article “How it really was” by L.F. Zykin (pp. 217-25).
Full translation:
Thank you for the chance to read L.F. Zykin’s manuscript of  reminiscences about one of  the 
challenging periods for workers at the Turkmen AP Station.
Reminiscences are always subjective and emotionally colored, which places a certain 
responsibility on the authors and requires gentleness and accuracy, especially when talking not 
only about the fate of  people, but about problems of  the group. In this regard, I would like 
to note that the anti-plague system is a rare example of  close collaboration and unity between 
science and practice.
At your request, I shared the manuscript with E.A. Moskvitina and L.S. Podosinnikova. During 
the 1970s and 1980s, they worked with specialists from Turkmen AP Station on cholera 
epidemiological surveillance taking into account the properties of  El Tor vibrios isolated 
from Turkmenia. Podosinnikova also participated in the multifaceted study of  the reversal of  
virulence in El Tor vibrios found in water bodies in cholera-free areas, including Turkmenia, 

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and also participated in the commission that verified the results of  this work in 1978. We would 
like to note a certain bias of  Zykin in describing a complicated time for public health science 
and  practice  in  evaluating  the  epidemiological  significance  of   cholera  vibrios  from  surface 
waters. The article contains irritating inaccuracies, hence the bias expressed in the title. In fact, 
everything was more complicated than Zykin describes, but there was no standoff  between 
science and practice. Neither scientists nor practitioners were able to provide factual data on 
the “safety” of  the strains. They did not have suitable tools to do this. V.I. Svyatoy was not the 
only person who had this intuition.
The possibility of  differences in the “local” El Tor vibrio strains isolated from waters in 
Turkmenia was first raised by R.S. Zotova, a scientist at Turkmen AP Station, in her dissertation 
work in 1969. In the 1970s, this work was continued by V.I. Svyatoy, a scientist at the same AP 
station, who examined a large number of  cholera vibrio strains of  local origin and showed that 
they were “weakly” virulent or were not virulent. However in those years, it was impossible to 
distinguish them from dangerous pathogens that had entered the water and lost their virulence. 
A situation similar to that in Turkmenia took place in the Sochi area, where, since 1969, cholera 
vibrios were isolated from certain rivers every year, although there were no cholera outbreaks.
Specialists from all institutions of  the anti-plague system searched for criteria to differentiate 
“dangerous” strains. Proof  of  this is shown by the collaborative research done during 1973-78 
by all the AP institutes and Turkmen AP Station, as well as the commission at Mikrob in 1978 
organized by the USSR MOH to investigate the possibility of  reversal of  virulence in strains 
isolated from cholera-free areas. This work failed to show that the strains isolated from waters 
in Sochi, Turkmenia, and other cholera-free areas could become virulent.
In the 1980s, based on the synthesis of  data on cholera vibrios isolated from various 
environmental features in different areas of  the USSR (Moldavia, Ukraine, Russia, Armenia, 
Azerbaijan, Turkmenia, Uzbekistan, and others), the Rostov AP Institute, as the lead institute 
for cholera, with the participation of  leading specialists from other institutes, submitted to 
the Main Administration for Quarantine Infections, USSR MOH, data that became the basis 
for  “Instructions  for  Organizing  and  Conducting  Cholera  Control  Measures”  (1981).  This 
document established preventive measures, i.e., measures to identify cholera vibrios from 
environmental features, which, back then, helped reduce the social and economic costs of  
cholera epidemic surveillance.
The sorting of  cholera vibrio strains into epidemically significant ones that have the cholera 
toxin gene versus non-epidemic strains (without this gene) became possible only in the 1980s 
with the introduction of  the molecular probe method. Following on the work by American 
researchers who showed that the Vct– strains are not pathogens of  epidemic cholera, this 
method was used by specialists in this country (G.M. Grizhebovsky, V.P. Vlasov, Ye.V. 
Monakhov, A.F. Bryukhanov, and others). The analysis of  this characteristic for strains isolated 
in the USSR during the seventh pandemic in areas with different epidemiological situations 
(L.S. Podosinnikova) made it possible to evaluate the epidemiological situation in areas where 

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Vct– cholera vibrios had been isolated every year, in order to develop the basis for dividing 
the country into zones by type of  cholera epidemic (E.A. Moskvitina), and also in order to 
propose differences in the extent of  measures to be taken when cholera vibrios with different 
toxicities are isolated from patients.
Thus, the experience and factual data of  practicing public health workers, supplemented by 
scientific research using new methodologies, served as the basis for the changes of  tactics for 
conducting cholera prevention and control measures as formulated in standard documents, 
first in 1991, “Instructions for Organizing and Conducting Cholera Control Measures,” USSR 
MOH  Order  No. 390 of  October 1, 1990, and later, in the next edition of  the document 
published in 1995 under the same title.
In addition, to placing V.I. Svyatoy in opposition to all the specialists of  the system, several other 
inaccuracies found their way into Zykin’s article, in particular, the rejection of  the theoretical 
basis of  the possibility of  using the phage method to evaluate the virulence of  cholera vibrios. 
At a certain stage during a period of  over 15 years, this method was very convenient for practical 
public  health  purposes  because  of   the  difficulty  of   experimentally  evaluating  virulence.  The 
resistance to phages became a hindrance to the method only in the 1990s.
This, briefly stated, is the viewpoint of  specialists of  the lead institute for cholera concerning 
the very complicated issue of  the 1970s and 1980s of  evaluating cholera epidemics in different 
areas and determining the epidemic significance of  strains isolated from surface waters. This is 
somewhat different from Zykin’s subjective bias expressed in each word of  this article, because 
of  which it is hardly worth publishing.
Institute Director, Honored Scientist of  the Russian Federation,
Academician of  the Russian Federation Academy of  Natural Sciences,
Professor Yu.M. Lomov
In Response to the Request Concerning the Article by L.F. 
Zykin
R.T. Gerasimenko (p. 231)
Commentary on the article “How it really was” by L.F. Zykin (pp. 217-25). 
Full translation:
… I agree with everything that is said and no changes are needed. If  possible, please mention 
the physician L.I. Alieva in the section concerning the rabbit experiments. She was a virtuoso 
in the laboratory work of  infecting rabbits and mice.

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How It Was Proven That the Cholera Outbreak in 1965 Was 
Caused by El Tor Vibrio
Leonid Fedorovich Zykin (p. 232-38)
This chapter describes the investigation of  a cholera outbreak in Kara-Kalpak that began in the summer of  1965 
and lasted through early 1966. It discusses how the El Tor bacterium was identified as the cause of  the outbreak and 
describes the controversy concerning these findings.
Isolation of  Cholera Toxin by Soviet Scientists
Leonid Fedorovich Zykin (pp. 239-51). 16 references, one photograph.
This chapter describes developments in cholera research by the author and others from the 1960s through 1990s. It also 
discusses the changing theories on the nature of  cholera toxin and its effects on animal models. Last, it describes the 
development of  a cholera vaccine and diagnostic test.
Forgotten Photographs
M.I. Levi, Yu.G. Suchkov (pp. 252-94). 42 photographs.
This section contains photographs (group and individual portraits) of  researchers and other AP system personnel that 
were taken during the 1930s through the 1990s. Most photographs are undated.
Plague Vaccine Strain Yields a Thermobiotic
M.I. Levi (pp. 295-97). 1 figure.
This chapter is, in effect, an abstract of  recent research findings that demonstrate that the EV vaccine strain of  the 
plague bacterium produces a thermobiotic similar to that produced by Bacillus stearothermophilus.
Index of  Names in Volume 7
pp. (302-13)
Not included in this paper. 

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v
oLuMe
 8 (1998)
Foreword
Moisey Iosifovich Levi (p. 3)
Introduction to the eighth volume of  the “Interesting Stories...” series.
Full translation:
Life goes on, and now, dear readers, the Eighth Volume of  the Interesting Stories… is in your 
hands.  Our  cellar  of   memories  is  nearly  bare,  “some  are  far  distant,  some  are  dead….”
83
  
Therefore,  along  with  historical  articles,  we  are  publishing  thorough  scientific  reviews  and 
original fundamental research. Even in these articles, we are trying to include elements in the 
lives of  institutions and individual scientists.
The mainstream media have noticed us; in particular, the monthly Sovershenno Sekretno, no. 10, 
1998, published a long article by T.M. Belousova entitled “Plague.”
84
In this volume, we acknowledge the 80th anniversary of  the announcement, although not 
the actual founding, of  Mikrob in Saratov. This institution occupies a glorious and honored 
position in the AP service.
We will be grateful to our readers for any comments and criticisms about the published 
materials.
M.I. Levi, Editor
High-Risk Infections in the Research of  Zinaida Vissarionovna 
Yermolyeva
Elena Alekseevna Vedmina (p. 4-21). Four photographs.
This  chapter  is  a  biographical  sketch  of   Z.V.  Yermolyeva,  a  prominent  microbiologist  and  administrator,  which 
highlights her laboratory research and fieldwork with high-risk infections, including cholera and plague.
83
  This is a line by the thirteenth-century Persian poet Sadi which Aleksandr Pushkin cites in the final stanza of  his epic 
poem, Eugene Onegin: “Of  those who heard my opening pages / in friendly gatherings where I read, / as Sadi sang in earlier 
ages, / ‘some are far distant, some are dead,’” (1979 Charles Johnston translation).
84
  A translated version of  this article is included in Part II of  this paper.

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