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CHAPTER THREE

EMERGENCE OF MOLECULAR BIOLOGY

vreprtoted

 
- 87 -

Microbiology. Compared with other biological sciences, micro-
biology has been characterized by W. Braun in his text on bacterial
genetics as ''one of the last strongholds of Lamarckianism. n2low
panel appointed by the National Academy of Sciences (U.S.A.) ex-
plained the reasons for this as follows:

Because of their biological material and

their divorcement from the mainstream of
genetic thinking, bacteriologists were often
led to adopt a Lamarckian view of inheritance
long after this model had been rejected by a
majority of the biological community. Micro-
biologists had, for many years, been greatly
impressed with the apparent genetic plasticity
of microorganisms. It was, for example,
easily possible to develop cultures that were
resistant to various lethal agents simply by
including them in the growth medium. Simi -
larly, cultures capable of utilizing the sugar
lactose could readily be derived from non-
utilizers by passage.through media in which
lactose was the principal source of carbon and
energy. It seemed that virtually any specific
change desired could be brought about by intro-
ducing the proper agent. The feeling thus arose

\, that these agents were causing instructional
changes in the genetic makeup of the organism....
A series of ingenious experiments were per-
formed to determine whether selective agents
played any directive role in bacterial mutations.
The first involved resistance to bacterial viruses
and established that the resistant mutants found
in a series of independent cultures grown in the
absence of virus indicated that a heritable modifi-
cation leading to resistance occurred randomly in
the absence of the lethal selective agent. To such
experiments were added others using the method of

 

2lw, Braun, Bacterial Genetics (W. B. Saunders: Philadelphia,
1953), p. 32.
- 88 -

replica plating, which permitted the isolation
and identification of pure resistant clones...
from cultures that had never been exposed to
the lethal agent. Bacteriology was no longer
the last stronghold of Lamarckism.

' The experiments referred to above were those of S, Luria and M. Del-
bruck (1943) and of J. Lederberg and E, M, Lederberg (1952), but they
did not totally dispel the view that some acquired characteristics in
bacteria were heritable. As Edward Adelberg noted: ''The Leder-
bergs' experiments convinced even the strongest supporters of the
theory of directed variation the 'pre-adaptive' mutants exist, but not

that such mutants account for all of the resistant cells which are re-

vealed by a drug. 23

Conclusive evidence was finally provided in 1955 by L. L. Ca-

valli-Sforza and J, Lederberg. a4 But even in the late 1950s such

22 Biology and the Future of Man, ed. by Philip Handler (Oxford
‘University Press: New York, 1970), pp. 20, 22. The panel on mole-
cular biology consisted of Sol Spiegelman (chairman), K. C. Atwood,
Paul Berg, Edwin S. Lennox, Cyrus Levinthal, and Charles A.
Thomas, Jr.

23Edward A. Adelberg, "Introduction", Papers on Bacterial
Genetics (2nd ed.; Little, Brown and Co.: Boston, 1966), p. 2.
The experiments referred to are: S. E. Luria & M. Delbruck, "Muta-
tions of Bacteria From Virus Sensitivity to Virus Resistance", re-
printed ibid., pp. 75-95, originally in Genetics, 1943, pp. 491-511;
and J. Lederberg and E. M. Lederberg, "Replica plating and indirect
selection of bacterial mutants", Journal of Bacteriology, 1952, p. 399.

 

 

244, L. Cavalli-Sforza & Joshua Lederberg, "Isolation of Pre-

Adaptive Mutants in Bacteria by Sib Selection", Genetics, 1956,
pp. 367-381; reprinted in Papers on Bacterial Genetics, pp. 96-110.
- 89 -

Western workers as A. C. R. Dean and C. Hinshelwood believed and
were attempting to prove experimentally that exposure to some factors
in a culture medium could cause a "physiological reconstruction" with-
in the cell which, if sufficiently prolonged, could result in heritable
modification. 2

Such opposition to the predominant views of bacterial geneticists
was not extensive in the West, but its continued existence demonstrates
that a belief in the possible inheritance of acquired or environmentally
induced characteristics had intellectual roots in microbiology which had
nothing to do with Lysenko's theories. The."expulsion" of Lamar-
ckianism from Western microbiology, if it pceurred at all, took place
in the mid-1950s. Even today the scientific language used by micro-
biologists includes artifacts of these Lamarckian conceptions: Mpacte-
rial adaptation", "training''a culture, 'inducing'' resistance, ‘adaptive
variation", and so forth.

These facts are helpful in understanding why bacterial genetics

was not wholeheartedly embraced by many leading Soviet microbio-

logists. True, the development of Soviet bacterial genetics was not

 

254, C. R. Dean & C. Hinshelwood, "Aspects of the Problem of
Drug Resistance in Bacteria", in Drug Resistance in Micro-Organisms:
Mechanisms of Development, ed. by G. E. W. Wolstenholme &
C. M. O'Conner (Little, Brown & Co.: Boston, 1957), p. 4. On this
point, for the account of their work by a Soviet microbiologist who
visited London in March, 1957, see N, D. Ierusalimskii, 'Simpozium
po adaptatsii mikroorganizmov k lekarstvennym veshchestvam v Anghii",
- Vestnik Akademii nauk SSSR, 1957, No. 7, pp. 58-61.
-~ 90 -

totally stymied: such geneticists as S. M., Gershenzon, S. I. Alik-
hanian, and V. L. Ryzhkov, who by the early 1940s had already begun
work on bacterial or viral genetics, continued it in the 1950s ina
variety of institutional settings. 7° But such work did not develop very
extensively at the main Soviet center of microbiological research, the
Academy's Institute of Microbiology, and the reasons can be traced in

the writings of its director.~!

 

26s. M. Gershenzon worked in his laboratory of microbiology in
the Institute of Zoology of the Ukrainian Academy of Sciences in Kiev;
after 1966, this laboratory was expanded into a new Institute of Micro-
biology and Virology. S. I. Alikhanian headed a laboratory in the In-
stitute of Antibiotics within the Ministry of Health and, after 1958, a
laboratory in the Radiobiology Division of the Kurchatov Institute of
Atomic Energy. V. L. Ryzhkov had been eiected a corresponding
member of the Academy in 1946. Beginning in 1961, their views ap-
peared with greater frequency in Vestnik: see, for example,
V. L. Ryzhkov, "Fiziologiia virusov i khimioterapiia virusnykh
boleznei", Vestnik Akademii nauk SSSR, 1961, No. 8, pp. 59-63; and
S. M. Gershenzon, 'Molekuliarnye osnovy reproduktsii i izmenchi-
vosti virusov", ibid., 1964, No. ll, pp. 71-77.

270n the work of the Institute during the period, see "Ob aktiv-
nom izmenenii uslovii sredy mikroorganizmami", Vestnik Akademii
nauk SSSR, 1955, No. 8, pp. 98-99; '"'V Institute mikrobiologii', ibid.,
- pp. 78-79; ''V Institute mikrobiologii'', ibid., 1956, No. 8, pp. 90-91;
"Ispol'zovanie mikrobiologicheskikh protsessov v promyshiennosti",
ibid., 1957, No. 8, pp. 109-111; "Razvitie sovetskoi mikrobiologii",
ibid., 1964, No. 7, pp. H1-113; and the annual reports appearing in
Vestnik and Izvestiia Akademii nauk SSSR (biol. otd.) by Nesmeianov,
Keldysh, Topchiev, Engel'gardt, and Sisakian. Such research did
take place ona rodest scale, however, especially in the laboratories
of M. N. Meisel! and N. D. lerusalemskii, but it only achieved pro-
per scope after 1966 when N. D. Ierusalemskii was made director of
the institute of microbiology and virology in the Pushchino complex.
- 9] -

Aleksandr Aleksandrovich Imshenetskii (1905- ) became the
director of the Institute of Microbiology in 1949 - months after the
August session - and held the post at least through the late 1960s.28
In that capacity, he attended many international conferences on micro-
biology and genetics, and made lecture tours in England and the United
states.29 He was also primarily responsible for articulating in Aca-
demy publications the successes and goals of Soviet microbiology.

. His writings from 1955 through the early 1960s indicate almost
no awareness of the importance of work on bacterial induction, trans-
duction, and phage genetics. Concerning these, his article in 1955 on
'The Longrange Future of Microbiology" contains only the following
rather confused passage:

This touches upon the method of the so-
called "induction" of the properties of one
species of microbe in another. Work of
this sort is not always irreproachable me-

thodologically, since the action of the living
products of one species on another sometimes

280On his career through 1967, see Aleksandr Aleksandrovich
Imshenetskii, Akademiia nauk SSSR, Materialy k biobibliografii
uchenykh SSSR (Nauka: Moscow, 1967).

 

29 For reports on trips to Japan, England, Sweden, the United
States, and Canada, see his articles 'Geneticheskil simpozium v
Japonii", Vestnik Akademii nauk SSSR, 1957, No. 1, pp. 63-67;

VW mikrobiologicheskikh uchrezhdeniiakh Anglii", ibid., 1958, No. 4,
“pp. 66-68; "Mezhdunarodnyi mikrobiologicheskii kongress", ibid.,
No. ll, pp. 69-72; "Mikrobiologicheskie issledovaniia v SShA", ibid.,
1961, No. 6, pp. 72-75; and "VII Mikrobiologicheskii kongress",
ibid., 1963, No. l, pp. 66-69.
~ 92 -

yields a new form corresponding to a third
species. Hence, the specificity of these
variations remains unproven, Frequently,
such investigations relate to pathogenic
microbes, in which species specificity rests
on extraordinarily minute differences. In
such species ''fractions'" the transition from
one species to another has been achieved, but
these transitions can sometimes occur even
without any induction of properties as a result
of the laboratory life of the microbe, i.e. by
the action of the sum total of factors to which
they are exposed in laboratory conditions.
Only further profound study of the metabolism
of microorganisms can lead to a mastery of
the means to directionally vary their bio-
chemical activity.

This article, and in particular the passage cited above, were strongly
criticized by R. L. Ryzhkov ina letter to the editors of Vestnik. Ryzh-
kov took issue with Imshenetskii for ignoring foreign work on recombi-
nation, transformation and the hereditary mechanism in bacteria and
phage, results which "whether you like them or not...are perfectly
precise, have been verified in a whole series of laboratories and con-
stitute a fundamental revolution in our conceptions of the development

_of microbes.... ol

In his article, Imshenetskii was expressing the views of a tra-

ditional microbiologist rather than of a bacterial geneticist: he dwelt

30A. A. Imshenetskii, 'O perspektivakh razvitiia mikrobiologii',
Vestnik Akademii nauk SSSR, 1955, No. 6, p. 47.

3ivion. Ryzhkov, "Pistmo v redaktsiiu: K voprosu o perspcekti-
vakh razvitiia mikrobiologii", ibid., 1956, No. 1, p. 123.
-~ 93 -

on problems of species definition, was impressed with the great
variability and plasticity of bacteria, and believed their properties
could be changed by factors in the environment, although he was vague
as to the mechanism. Ina report ona genetics symposium in Japan
in 1956, he was highly skeptical of using such words as transduction,
crossing-over, sexuality, genes and DNA in describing processes
occurring between bacteria and phage, commenting: "There is not the
slightest doubt that such conclusions and analogies have little founda -
tion and are highly speculative in character. 32 But he continued:
"Yet it would be incorrect because of this not to recognize the achieve-
ments of genetics, of which it is justly proud. The functional-morpho-~
logical method for the study of the nucleus and chromosomes has
brought forth very much of value...and we should develop these ap-
proaches, more rapidly. 133° In his other writings, whenever he dis-
cussed such Western results, he usually emphasized the works of Dean
and Hinshelwood, and continued to be skeptical not only of the validity

32a. A, Imshenetskii, 'Geneticheskii simpozium v Iaponii",
ibid., 1957, No. 1, p. 67.

33ypid.
- 94 -

of the results-of bacterial genetics, but also of their usefulness. 34
One gets a feeling that he simply does not regard such work as the

province of microbiology.

One of Imshenetskii's remarks is especially relevant to this
point:

Twenty years ago in a conversation with
the author of the present article, an out-
standing Soviet botanist expressed the view
that the study of biological structures less
than one tenth of a micron in size is already
the task of the physicist, not of the biologist.
Now, in connection with the problem of the
localization of various enzymes inside the
cell, the electron microscope is aiding the
study of biochemical activity and morpho-
logy of granules which are substantially
smaller,

34On Hinshelwood, see A. A. Imshenetskii, 'V mikrobiolo-
gicheskikh uchrezhdeniiakh v Anglii", ibid., 1958, No. 4, p. 67.
On the lack of utility of such work, see A. A. Imshenetskii, ''O neko-
torykh zadachakh selektsii mikroorganizmov", ibid., 1959, No. 10,
pp. 32-38; A. A. Imshenetskii, 'Mikrobiologicheskie issledovaniia v
SShA", ibid., 1961, No. 6, pp. 72-75, where he comments, '™The
connection between genetic investigations and microbial selection is
very weak, and the theoretical bases of selection have been elaborated
only poorly" (p. 75); A. A. Imshenetskii, "VIII Mikrobiologicheskii
kongress", ibid., 1963, No. 1, pp. 66-69, where he comments, ''How~
ever, from all those who entered into discussion on the importance of
genetics in technical microbiology, it became perfectly clear that
theoretical genetics, which has given so much to our understanding of
the general laws of heredity and variability, is very far removed from
the demands of practice" (p. 68); and "Aktual'nye zadachi mikrobio-
logii", ibid., 1963, No. 3, pp. 82-90.
-95-

It would be incorrect to speak of the mole-
cular biology of microbes, but it is possible to
study the living processes of the microbial cell
occurring on the molecular level, and itis being
conducted along a broad front.

Imshenetsxii was not alone in these views. Similar motifs frequently
appeared in the writings of other Soviet microbiologists during this |
period: skepticism towards Western results; belief in the inheritance
of acquired bacterial characteristics; concern with species delinea-
tions; emphasis on the views of Dean and Hinshelwood when discussing
Western work; and the tendency to view developments in bacterial and
biochemical genetics as somehow not directly relevant to the practical

tasks of microbiology. 36

Such views obviously have a great similarity with those of
Lysenko, whose theories emphasized the possibility of the inheritance
of acquired characteristics by means of the "assimilation" by the

organism of changed external conditions, occasionally making possible

i

leaps from one species into another. 3? But it would be a mistake to

354, A. Imshenetskii, "Sovremennye zadachi obshchei mikro-
biologii', ibid., 1961, No. 10, pp. 46-47.

36For example, see N. N. Zhukov-Verezhnikov, "O znachenii
mikrobiologicheskikh dannykh dlia razrabotki teorii vidoobrazovaniia",
Voprosy filosofii, 1957, No. 2, pp. 117-127; and N. N. Zhukov-Verezh-
nikov & A. P. Pekhov, "Genetika mikroorganizmov i sovremennye
vzgliady na sushchnost' nasledstvennosti", ibid., 1958, No. 6, pp. 127-
138.

37See, for example, T. D. Lysenko, Agrobiologiia (Moscow,
1952); "Novoe v nauke o biologicheskom vide", Botanicheskii zhurnal,
1953, No. 1, pp. #4-56; and ''Teoreticheskie osnovy napravilennogo
izmeneniia nasledstvennosti sel'sko-khoziaistvennykh rastenii", Prav-
da, January 29, 1963, pp. 3-4.

 
- 96 -

see the views of these microbiologists as identical to those of Lysenko,
who in fact criticized what he regarded as their excessive Lamar-
ckianism:

The more I familiarize myself with the
situation in this field of biology, the more
obvious it becomes to me that many of our
outstanding scientific workers in micro-
biology, even those who consider themselves
partisans of Michurinist biology, have hitherto
adopted positions with regard to the so-called
adaptive variability of microorganisms which
are essentially Lamarckian in nature.

It is well-known that Lamarckism is closer
to the truth than Weismannism in all its old
and new variants.... But neither the earlier
Lamarckism nor the current theory of adaptive
variability of microorganisms can correctly
explain the development of the living world....

Idealists and mechanicists in biology con-
sider that the quality of hereditary variability
does not depend on the quality of the factors
acting. Hence they say that no sort of adaptive
‘variability exists and that those forms and
strains of microorganisms which are resistant

~ to one or another antibiotic or medicinal sub-
stance are derived from non-resistant ones,
not by means of adaptive variation, but by
means of the selection and reproduction of re-
sistant forms already present in the popula-
tion....Against such arguments the partisans
of Lamarckism are powerless.... Why don't
our microbiologists who consider themselves
Michurinists maintain Michurinist positions on
these questions ? 38

There is no need to dwell on Lysenko's ''Michurinist" explanation,

based on his law of "adequate variability" [adekvatnaia izmenchivost']

387. Dp. Lysenko, ''Za materializm v biologii', Voprosy filo-
sofii, 1958, No. 2, pp. 109-110.
- 97 -

but itis interesting that he regarded views such as those expressed by
Imshenetskii as more Lamarckian than Michurinist. It thus seems
likely that at least part of the resistance to molecular biology among
Soviet microbiologists came from firmly rooted intellectual traditions
of the discipline.

Biochemistry. Biochemistry played a greater role in the emer-
gence of molecular biology in the Soviet Union than any other discipline.
The field's importance can be seen from the following fact: from
Lysenko's ascendancy in 1948 through the Academy re-organization of
1963, every Academic Secretary of the Division of Biological Sciences
was a biochemist.

Following the 1948 session, Lysenko's supporter A. I. Oparin
became the head of the division, and during the subsequent years he
presided over the dissolution of genetics research within the division.
In 1956, his colleague from the Institute of Biochemistry, V. A. Engel'-
gardt replaced him and worked actively to re-establish genetics and
create conditions for the rapid development of Soviet molecular bio-
logy. Finally, from 1959 through 1963, their colleague N. M. Sisakian -
also from the Institute of Biochemistry - presided over the division.

As we shall see, Engel'gardt's role is relatively unambiguous,
he was a consistent and outspoken supporter of molecular biology and
molecular genetics. The same cannot be said of Oparin and Sisakian,

however. From 1948 through the mid-1950s, both strongly supported