J Mol Evol
DOI 10.1007/s00239-016-9773-5
ORIGINAL ARTICLE
Alexandr I. Oparin and the Origin of Life: A Historical
Reassessment of the Heterotrophic Theory
Antonio Lazcano1
Received: 21 November 2016 / Accepted: 24 November 2016
 Springer Science+Business Media New York 2016
Abstract The heterotrophic origin of life proposed by A.
I. Oparin in the 1920s was part of a Darwinian framework
that assumed that living organisms were the historical
outcome of a gradual transformation of lifeless matter.
Eighty years ago, he presented a much more detailed
scheme of the processes that may have led to life. As
argued here, the development of the heterotrophic theory
has been shaped by an entangled scenario in which a
number of technical and scientific developments concur, as
well as non-scientific issues including the Stalinist period
and the tensions of the Cold War atmosphere. What has
been largely ignored until now is the key role played by
Haeckels ideas in shaping Oparins theory. The hetero-
trophic theory has been erroneously described as a meta-
bolism-first hypothesis in which genetic material was not
included due to ideological pressures of the Soviet gov-
ernment. As shown here, both characterizations are mis-
taken. The development of Oparins views and the ensuing
debates cannot be understood without considering the
confrontation between Mendelism and Darwinism during
the first three decades of the past century, combined with
the doubts surrounding the existence of genes.
Keywords Oparin
Heterotrophic theory
Mendelism

Origin of life
& Antonio Lazcano
alar@ciencias.unam.mx
1 scientific criticisms have been raised against Oparins
Miembro de El Colegio Nacional, Facultad de Ciencias,
UNAM, Apdo.Postal 70-407, Cd. Universitaria,
04510 Mexico City, Mexico
Introduction
Eighty years ago, the Russian edition of A. I. Oparins
book the Origin of Life was published in Moscow.
Although it had the same title of the 1924 monograph in
which he first presented his proposal of a heterotrophic
origin of life, the depth and the extent of the 1936 book
were substantially different. In his 1936 book, Oparin
presented a detailed description of the processes that may
have led to the emergence of the first living beings based
on evidence drawn from a wide range of scientific fields,
astronomy, chemistry, geology, planetology, biochemistry,
microbial physiology; all developed in a surprisingly
coherent picture of evolution that started with the synthesis
of organic compounds in a highly reducing primitive Earth,
followed by a process of precellular evolution that led to
the emergence of primordial anaerobic heterotrophs.
Two years later, the English translation of the book was
published in the USA. It soon got a favorable review by the
Russian-born USA biochemist William S. Malisoff, who
accurately described it in the May 29, 1938 New York
Times issue as a semi-popular summary of the subject that
would be a landmark for discussion for a long time to
come. Oparins book rapidly caught the attention of a
number of major scientists, including John D. Bernal,
Norman Pirie, Norman Horowitz, and Cornelius van Niel,
who realized that Oparins scheme not only explained how
life could have appeared but could also be the basis of a
meaningful classification of bacteria (van Niel 1946).
Perhaps not surprising for a book published during the
suffocating atmosphere Stalinist era by an author who was
part of the Soviet establishment, a number of political and
views. As argued here, the heterotrophic theory has been
shaped by an entangled scenario that in which a number of
123

technical and scientific developments that included space
exploration, the extended misconception that bacteria
lacked genes (whose actual existence was doubted by
many), the birth of molecular biology, and its initial con-
frontation with biochemistry and cell biology as well as
non-scientific issues that included the hardships of the
Stalinist period, including the pernicious influence of
Lysenko and his followers, the distrust of Soviet scientists
by many Western scientists, and the tensions of the Cold
War atmosphere (Lazcano 1992, 1995; Fry 2002).
Although a number of analyses of the genesis of Opar-
ins proposal have been published that have led to the
recognition of the scientific and political influences that
shaped them (Graham 1972, 1993; Farley 1977; Fry 2002;
Lazcano 2010; Falk and Lazcano 2012), what has been
largely ignored until now is the key role played by
Haeckels ideas in shaping Oparins theory. His hetero-
trophic theory has been erroneously described as a meta-
bolism-first hypothesis (Bedau and Cleland 2010) in which
genetic material was not included due to ideological
pressures of the Soviet government (Muller 1961; de Duve
1991). As shown here, both characterizations are mistaken.
The development of Oparins views and the ensuing
debates cannot be understood without considering the
confrontation between Mendelism and Darwinism during
the first three decades of the 20th century, combined with
the doubts surrounding the existence of genes. Oparins
ideas were shaped not only by the adoption of Haeckels
scheme of evolution that started with the formation of the
Solar System and the Earth itself, but also by the view that
in bacteria, or Monera in Haeckels original terminology,
the protoplasm was the organ of both inheritance and
nutrition (Lazcano 2016). As summarized here, Oparin was
far from being the only one who assumed that this was the
case. In this paper, I discuss these issues, as well the
intricate political interpretation of Darwins theory in the
USSR during the periods that shaped the heterotrophic
theory of the origin of life.
Darwinism as a Political Battle Cry
As shown by the writings of Nikolai N. Strakhov, a
renowned 19th century philosopher and literary critic, by
the time the first Russian translation of Origin of Species
was published in 1864, Darwins ideas had already gained
considerable attention in academic and were also well
entrenched among social reformists. Together with Stra-
khov, Kliment A. Timiriazev, a prominent plant physiol-
ogist and agronomist well known for his liberal political
views, became the main popularizer of evolutionary ideas.
Thanks to his efforts, Darwinism played a major role in the
development of a secular atmosphere and soon became an
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J Mol Evol
essential component of Russian philosophical attempts to
develop a materialistic ontology of science (Vucinich
1988; Kolchinsky 2008).
Darwins ideas in Russian though were not limited to
science and philosophy, but rapidly became part of the
ideological discussions that characterized the politically
charged atmosphere at the turn of the 20th century. The
association of Darwins writings with liberal political ideas
was rapidly transformed into a battle cry of the radical
younger intelligentsia. This included the Russian Marxists,
who attempted to demonstrate that Darwins philosophical
premises should be considered as part of the ideological
struggle against the autocratic Czarist regime. This was
summarized in Georgy V. Plekhanovs statement that
logically, Marxs investigation begins precisely where
Darwins ends, and reinforced by Lenins declaration that
militant materialists should join forces with natural scien-
tists, a statement that reinforced the search for secular
explanations of biological phenomenon and the political
interpretation of evolutionary ideas (Vucinich 1988).
As documented by Bowler (1988), towards the end of
the 19th century Darwinian explanations based on natural
selection were increasingly criticized, and alternative pro-
posals based on Mendelism and other mechanisms were on
the rise. This was not the case of Russia. As A. O. Ko-
valevskii, an influential Russian embryologist, wrote in the
late 1860s, Darwins theory was received in Russia with
profound sympathy. While in Western Europe it met firmly
established old traditions which it had first to overcome, in
Russia it appearance coincided with the awakening of our
society after the Crimean War and here it immediately
received the status of full citizenship and ever since has
enjoyed wide popularity (cf. Graham 1993). Mendelism
and Hugo de Vries mutation theory had few followers, and
as their confrontation against those advocating natural
selection, Darwinism become a component of the official
ideology of the USSR. Timiriazev, who was nicknamed
Darwins Russian bulldog, explicitly stated after the 1900
rediscovery of Mendels laws of inheritance that the
Mendelians and mutationists were the main targets of his
war on anti-Darwinists (Vucinich 1988)long before
Lysenkos merciless attacks on genetics.
In 1861, an anonymous essay published in the Russian
Library for Reading stated that the greatest contribution
of the Origin of Species in its setting the stage for a sci-
entific study of the origin of lifethe greatest of all mys-
teries (Vucinich 1988). The first to do so was Alexander I.
Oparin, a young biochemist who had joined the laboratory
of Alexei N. Bakh, an eminent scientist and political fig-
ure at the Karpov Physicochemical Institute. There he
worked on photosynthesis and, like many others, quickly
adopted the idea that metabolism was the outcome of
oxidation and reduction reactions that were coupled inside
J Mol Evol
cells and became aware of the extraordinary structural and
biochemical complexities of photosynthetic autotrophy
(Lazcano 2010).
Oparin was part of a generation that had grown up
experiencing the influence of the liberal, high-bourgeois
cultural and scientific circles of Saint Petersburg and
Moscow. He was also a convinced evolutionist. As a stu-
dent, he had attended the lectures given regularly by
Timiriazev, who had left the university in protest against
the Czarist government and due to his ill-health, and who
limited his meetings with students and colleagues to small
gatherings in his Moscow flat that Oparin attended. By the
time he graduated, his academic background included
natural history, biochemistry, and plant physiology, a
knowledge acquired within a research tradition strongly
committed to organismic, integral approaches in the anal-
ysis of natural phenomena. Oparin was not only well
acquainted with nearly all the literature on evolution
available in Russia, but, perhaps even more important, also
with the Darwinian method of comparative analysis and
historical interpretation of life features (Lazcano
1992, 2010).
For Oparin and many others, heredity was not concep-
tualized in terms of genes, whose existence was held in
doubt by many. The list of skeptics includes none other
than Thomas Hunt Morgan, who as late as 1933 stated that
there is no consensus of opinion amongst geneticists as to
what the genes arewhether they are real or purely ficti-
tious (cf. Cobb 2015). Like many of his contemporaries,
Oparin was convinced of the absolute incompatibility
between Mendelism and Darwinian evolution and accepted
Haeckels idea that in the Monera, biological inheritance
could be explained in terms of growth and division of the
bacterial protoplasm.
While Timiriazev supported Pasteurs rejection of
spontaneous generation and agreed that all extant life came
from life (Vucinich 1988), Oparin could not reconcile his
Darwinian credence in a gradual, slow evolution from the
simple to the complex, with conventional idea that when
life had appeared spontaneously, it was already endowed
with an autotrophic metabolism that included chlorophyll,
enzymes, and the metabolic ability to fix CO2 and to syn-
thesize organic compounds from it. Because a hetero-
trophic anaerobe is metabolically simpler than an
autotrophic one, the former would necessarily have
evolved first. Based on the simplicity and ubiquity of fer-
mentative reactions, Oparin argued that the first organisms
must have been heterotrophic bacteria unable to synthesize
their own food but fully dependent on the organic material
present in the primitive milieu, which he assumed was of
abiotic origin.
Development of this hypothesis led to his 1924 small
booklet The Origin of Life, where Oparin suggested that
the first living entities had been heterotrophic cells pre-
ceded by a slow and lengthy period of abiotic syntheses
and accumulation of organic compounds that had taken
place soon after the Earth was formed, a supposition
based on the presence of organic molecules in meteorites
and on the extraordinary 19th century corpus of synthetic
organic chemistry. Oparins commitment to a Darwinian
perspective is shown not only in his conclusion that the
universality of fermentation was evidence of a hetero-
trophic origin of life, but also in his proposal of a step-
wise, slow process of precellular evolution. The book can
be read as the work of a young and talented researcher
with abundant enthusiasm and free of intellectual preju-
dices, who was able to look for the first time beyond the
boundaries separating a wide different scientific fields,
from astronomy to biochemistry and cell biology (Miller
et al. 1997).
Ernst Haeckel: The Spontaneous Generation
of Monera
Although Darwins work had developed principles of his-
torical explanation that could be used to explain the
appearance of life, with one single known exception, he
refrained from publishing his ideas on this issue (Pereto
et al. 2009). This gap in the theory created an uncomfort-
able situation for many of his followers, including the
German naturalist Ernst Haeckel. Perhaps because of his
deep admiration of Darwin, at first, he limited his criticism
to a rather discrete footnote that he included in his mono-
graph Die Radiolarien, where he wrote that The chief
defect of the Darwinian theory is that it throws no light on
the origin of the primitive organismprobably a simple
cellfrom which all the others have descended. When
Darwin assumes a special creative act for this first species,
he is not consistent, and, I think, not quite sincere
(Haeckel 1862).
Few years later, Haeckel discussed the issue in consid-
erable detail in a chapter of his popular 1868 book The
History of Creation, in which he underlined the differences
between Lamarck and Darwin. While Lamarck had
accepted the possibility of spontaneous generation, wrote
Haeckel, Darwin passes over and avoids this subject, as
he expressly remarks that he has nothing to do with the
origin of the soul, nor with that of life itself. At the con-
clusion of his work he expresses himself more distinctly in
the following words: I imagine that probably all organic
beings which ever lived on this earth descended from some
primitive form, which was first called into life by the
Creator, a statement that Haeckel, who has severed all ties
with religion early in his life, found profoundly disturbing
and intellectually unsatisfactory (Richards 2008).
123

Haeckel was one of the first to look at microscopic life
from an evolutionary perspective. Based not only on the
availability of better microscopes, but also by his formid-
able understanding of biology; in 1866, he enlarged the
traditional two kingdoms taxonomy by creating the Pro-
tista, a third realm formed by microorganisms, which he
argued were ancestral to plants and animals. Although
along his career, Haeckel varied the taxonomic limits of his
newly created kingdom, he consistently included within the
bacteria and blue-green algae within the Monera, a Pro-
tistan subgroup that lacked a cell nucleus, which he had
speculated was the repository of heredity material
(Richards 2008). According to Haeckel, Monera were the
oldest biological group, in which the gel-like protoplasm
was the organ of both inheritance and nutrition.
Haeckels books had been translated into Russian long
before the Bolshevik Revolution, and Oparin was well
acquainted with his ideas (Lazcano 2016). Haeckel was
convinced that there was no essential difference between
the living and inert matter and that natural processes stand
in a material, causal, and historical connection. Since the
living and the non-living obey the same physical and
chemical laws, a direct link can be established between
them. Based on his monistic idea of the unity of Nature,
Haeckel proposed a secular scheme of evolution in that
included the spontaneous origin of life. Starting with
Kants nebular hypothesis for the origin of the Solar
System, Haeckel described the formation of the Earth and
the subsequent condensation of the primitive oceans. As
he wrote, [I]t was not till the earths crust had so far the unity of all Nature, and the unity of her laws of
cooled that the water had condensed into a fluid form, it
was not till the hitherto dry crust of the earth had for the
first time become covered with liquid water, that the
origin of the first organisms could take place. For all
animals and all plantsin fact, all organismsconsist in
great measure of fluid water, which combines in a pecu-
liar manner with other substances, and brings them into a
semi-fluid state of aggregation. We can therefore, from
these general outlines of the inorganic history of the
earths crust, deduce the important fact, that at a certain
definite time life had its beginning on earth, and that
terrestrial organisms did not exist from eternity, but at a
certain period came into existence for the first time
(Haeckel 1876).
As reviewed elsewhere (Lazcano 2016), Haeckel
explicitly assumed spontaneous generation of the
Monera and, as he wrote in The History of Creation,
[t]he differences which exist between the simplest
organic individuals and inorganic crystals are deter-
mined by the solid state of aggregation of the latter,
and by the semi-fluid state of the former. Beyond that
the causes producing form are exactly the same in both.
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J Mol Evol
This conviction forces itself upon us most clearly, if we
compare the exceedingly remarkable phenomena of
growth, adaptation, and the correlation of parts of
developing crystals with the corresponding phenomena
of the origin of the simplest organic individuals
(Monera and cells). The analogy between the two is so
great that, in reality, no accurate boundary can be
drawn (Haeckel 1876).
Now, how are we to conceive of this origin of the
first organisms?, asked Haeckel and added that Let us
see if in reality the origin of a first organism out of
inorganic matter, the origin of a living body out of
lifeless matter, is so utterly inconceivable and beyond all
experience. In one word, let us examine the question of
spontaneous generation, or archigony. In so doing, it is
above all things necessary to form a clear idea of the
principal properties of the two chief groups of natural
bodies, the so-called inanimate or inorganic, and the
animate or organic bodies, and then establish what is
common to, and what are the differences between, the
two groups, added Haeckel, [if] we assume the
hypothesis of spontaneous generation for the origin of
the first organisms, which in consequence of reasons
mentioned above, and especially in consequence of the
discovery of the Monera, has lost its former difficulty,
then we arrive at the establishment of an uninterrupted
natural connection between the development of the earth
and the organisms produced on it, and, in this last
remaining lurking-place of obscurity, we can proclaim
Development (emphasis in original, Haeckel 1876).
For Haeckel the unity of all Nature meant the evo-
lutionary continuity between the inorganic world and living
entities, but in the absence of a specific mechanism on how
the transition had taken place, he appealed to spontaneous
generation (Lazcano 2016). Oparin rejected this possibility,
and his reinterpretation of the available chemical data
within an evolutionary sequence was used to support his
proposal that the first organisms had been preceded by a
stage of prebiotic evolution during which the abiotic syn-
thesis of organic compounds taken place (Oparin 1924). In
doing so, he masterly separated the idea of spontaneous
generation of organisms from the chemical and biochemi-
cal origins of life. As John D. Bernal wrote many years
afterwards, what Oparin said about this process in his first
book was his most original contribution to the origin of
life, [that] is entitled From uncombined elements to
organic compounds. This is the forward-looking expla-
nation of the thesis which inspires the whole work. At that
time it was necessary to restate in modern terms the kind of
historic process which might have led to life appearing on
the Earth (Bernal 1967).
J Mol Evol
The Maturation of the Heterotrophic Theory
Oparin was not the only one who proposed a heterotrophic
origin of life. As reviewed elsewhere (Bada and Lazcano
2003), somewhat similar suggestions were made indepen-
dently in 1924 by the geochemist Charles Lipman and the
microbiologist R.B. Harvey, although they lacked the sci-
entific and methodological refinements of Oparins thesis.
Another proposal came from the Scottish polymath John B.S.
Haldane, who in a short article published in 1929 also sug-
gested that the origin of life had been preceded by the syn-
thesis of organic compounds. Based on experiments by the
British chemist E.C.C. Baly, who claimed that he had syn-
thesized amino acids and sugars by the UV irradiation of a
solution of CO2 in water, Haldane suggested that the absence
of oxygen in a CO2-rich primitive atmosphere had led to the
synthesis of organic compounds and the formation of a hot
dilute soup. He was keenly aware of DHerelles discovery
of phages and suggested that viruses represented an inter-
mediate step in the transition from the prebiotic soup to the
first heterotrophic cells. Life may have remained, wrote
Haldane (1929) in the virus stage for many millions of years
before a suitable assemblage of elementary units was
brought together in the first cell. When Haldane spoke of a
virus-intermediate stage between the prebiotic soup and the
first cells, he had in mind, like the American geneticist
Hermann J. Muller and many others, the possibility that
genes and viruses were the same and that proteins rather than
nucleic acids were the information bearers (Muller
1922, 1947).
Oparin published his first book during a period of major
social and political changes in the USSR. The late 1920s
were a chaotic period during which the Russian Academy of
Sciences was thoroughly restructured by the Bolshevik
leaders as part of the first five-year plan. This was a crucial
period for Soviet science during which many institutions
were created under the control not only of researchers but
also of state bureaucrats, which explicitly encouraged
dialectical materialism as scientific ideology. In 1927,
Oparin was appointed Professor of Biochemistry in the
University of Moscow, and that same year published
Chemical theory of of the origin of life in the Journal of
the Communist Academy of Sciences (Oparin 1927), the first
of his many essays and short books in which the signifi-
cance of Marxism to life sciences was addressed. Although
Oparin never joined the Communist Party, he rapidly
became part of the establishment and assisted his former
mentor Bakh in the creation of the Institute of Biochemistry,
where he worked on the biochemistry of tea and beets. In
1942, Oparin became Head of the Department of Plant
Biochemistry of the University of Moscow and four year
later, became full member of the Academy of Sciences and
Head of the Institute of Biochemistry, which was named
after Bakh.
Oparin had approached the origin of life problem in his
1924 pamphlet with intellectual versatility and admirable
fresh scholarship. His pioneering ideas on the primordial
character of anaerobic heterotrophs and on their subse-
quent evolution were a radical departure from the views
sustained by most of his contemporaries and represent an
attempt to extend Darwinian evolution to the non-living
chemical systems that preceded life. In retrospect, how-
ever, it is clear that his first pamphlet was the harbinger of
his meticulously researched 1936 volume. In his second
book, Oparin not only abandoned his nave and crude
materialism, but also provided a thorough presentation
and extensive analysis of the literature on the abiotic
synthesis of organic material. Based on a detailed analysis
of astronomical data, an extensive reinterpretation of
synthetic organic chemistry, and on the available data in
cell biology and microbial metabolism, in this new book,
he argued with clarity that the primitive Earth was a
highly reducing environment. Following Mendeleyevs
ideas on the origin of petroleum, Oparin argued that iron
carbides of geological origin had reacted with steam
forming hydrocarbons. Their oxidation would yield
alcohols, ketones, aldehydes, etc., that would then react
with ammonia to form amines, amides, and ammonium
salts. The resulting protein-like compounds and other
molecules would form a dilute solution, where they would
aggregate to form colloidal systems, such as coacervates,
from which the first heterotrophic microbes evolved
(Oparin 1936, 1938).
Oparins new volume was a strikingly original book and
reflects not only his intellectual maturation and the incor-
poration of the non-reductive principles of natural law
within the framework of a historical narrative. It also
echoes the changes in a society that was attempting to
develop science, art, and culture within the framework of
dialectical materialism (Graham 1993). But, those were
troubled times, a tortured and troubled epoch during which
the model of Stalinist science became entrenched and a
climate of intellectual and political repressions developed.
Stalins three major purges took place during the
19361938 period, and the price paid by Soviet society is
appalling. Huge numbers of artists, writers, and scientists
were victims of prosecutions and ideological censorship
during this period, which also marks the ascent of Trofim
D. Lysenko, a shrewd agronomist who soon gained the
favor of Stalin. And, yet, a number of scientists still
believed that the non-reductive principles of dialectical
materialism could shape the framework in which their
theories and explanations could be based. This was true not
only of the Soviet Union, but also in other countries where
123

a number of distinguished Western scientists, like J.
D. Bernal and J. B. S. Haldane, had similar goals.
In his second book, Oparin rejected not only the spon-
taneous generation Haeckel had termed archigony, but also
set himself apart from the efforts of Herrera, Leduc, and
other mechanistic materialists who attempted to explain the
origin of life by the mere coming together of organic
compounds. Certainly his writings have a period flavor, but
as underlined by Malisoff (1938), Oparin stressed the
materialist viewpoint of the evolution of life as matter. He
is a decided antimechanist. Those would confuse mecha-
nism with materialism will have much to learn from this
naturalistic-minded scientist and added that Life has origin of life was a mutationists attitude, not a Darwinian
neither arisen spontaneously nor has it existed externally. It
must have, therefore, resulted from a long evolution of
matter, its origin being merely one step in the course of its
historical development. This view was shared by many,
including Lanham (1952), who argued that Oparins 1938
book provides an exceptionally fine model of the appli-
cation of the historical (in the sense of evolutionary)
approach to basic biological problems, in contrast to what
has often been a purely mechanical approach.
In his 1936 book, Oparin rejected the possibility that
viruses represented primordial life forms because of their
strict dependence of cells to complete their biological
cycles and reiterated that biological inheritance was the
outcome of growth and division of coacervate drops. This
view, which appears to be rather nave from a contempo-
rary perspective, was nevertheless consistent with Haeck-
els position that, as noted above, had argued that the
Monera lack nucleus and traces of the hereditary sub-
stances found in other organisms. Oparin was not alone in
this idea. Johannsen had coined the word gene in 1909,
but had rejected the possibility that it was an actual phys-
ical entity, and in his 1933 Nobel Lecture, Morgan declared
that he was not sure of their existence (cf. Cobb, 2015), and
as late as 1942 Julian Huxley wrote that [] bacteria
have no genes in the sense of accurately quantized portions
of hereditary substances; and therefore have no need for
accurate division of the genetic system which is accom-
plished by mitosis (Huxley 1942).
The Search for a Primordial Gene
Driven by his secular convictions, the American physicist
Leonard Troland suggested in a series of papers published
from 1914 onwards that the first living being had been
nothing more than a catalytic, self-replicating molecule
which he that had suddenly appeared in the early oceans.
According to Troland (1914), this hypothetical primordial
genetic enzyme, which he identified with nucleoproteins
present in the cell nucleus (Fry 2006), was endowed with
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autocatalytic properties that allowed it to self-multiply, and
with heterocatalytic abilities from which metabolism arose.
It did not take long for Muller to modify Trolands
hypothesis and propose that the ancestral molecule had
been, in fact, a gene. Although the actual nature of genes
was still a mystery and many doubted their existence,
Muller argued that the first living entity had formed
abruptly and consisted of little more than a mutable gene,
or set of genes, endowed with catalytic and autoreplicative
properties (Muller 1926). He was a founding member of
Morgans fly room in Columbia University and fancied
himself as an evolutionist. However, his explanation of the
one (Lazcano 2010). Mullers proposal can be understood
in terms of his commitment to Mendelian genetics: given
the appearance of a genetic material capable of replication,
mutation and further replication of mutant forms, for
Muller evolution would automatically follow (Pon-
tecorvo 1982).
Neither Troland nor Muller predicted the catalytic
activity of nucleic acids nor should be considered precur-
sors of the RNA World hypothesis. As summarized by
Ravin (1977), at the turn of the 20th century, Goldschmidt
(1917) assumed that the rate of organ differentiation
depended on genetically determined differences in enzy-
matic activities, and instead of arguing that hereditary
factors determined enzyme activity, he hastily concluded
that the genetic factors of genes were the enzymes
themselves that resided in the cell nucleus.
Although they meet briefly, Muller and Oparin never
discussed their views on the origin of life (Falk and Laz-
cano 2012). Muller was a restless, imaginative scientist
who had moved to the USSR in 1933, convinced that sci-
ence could play a key role in shaping a better society. He
rapidly became disappointed with the dictatorial aspects of
Soviet life and Lysenkos influence in genetics and was
forced to leave the country in 1937. Ten years later, in his
famous Pilgrim Trust Lecture titled The Gene, Muller
(1947) wrote about Oparins proposal with considerable
sympathy: the idea, aptly expounded in detail by
Oparin (1938), that there must have been an extended
accumulation of ever more complex organic combinations,
permitted by the absence of living organisms that would
break them down, before genetic material could acciden-
tally arise from them and be suitable provided with the
components needed for its own reproduction.
Such appreciation did not last for long. By 1948, a
number of Soviet scientists had started to resist Lysenkos
growing influence and he reacted violently by closing
laboratories, firing researchers, and proscribing the teach-
ing of genetics. Oparin and many others have been accused
of conveniently overlooking the situation (Medvedev 1969)
as they went along with Lysenko and sailed uncomfortably
J Mol Evol
close to the wind. Because their survival depended on it, it
may be disingenuous to criticize them for their accom-
modation with Lysenko and the Soviet establishment
(Miller et al. 1997). Muller took a firm stand against
Lysenko and his minions, making the clash between him
and Oparin unavoidable. The result was an intense debate
characterized by sharp ideological and scientific exchanges
that reverberate to this day (Falk and Lazcano 2012).
Oparin was certainly ill-disposed against Mendelian
genetics, not only because of political reasons, but also
because he refused to accept the possibility that life
depended on the chance emergence of a single gene.
This led Muller to state that [the suggestion based on
Haeckel that] protoplasm had originated first and had
the capability of manufacturing not only the genetic
material but also its own complex organization The
Russian Oparin has since the early 1930s espoused this
view and has followed the official Communist Party line
by giving the specific genetic materials a back seat
(Muller 1966).
The growing antagonism between Oparin and Muller
can be explained not only by their philosophical and
political differences, but also in terms of the now largely
forgotten conflict between biochemistry and molecular
biology (Falk and Lazcano 2012). Although it took Muller
more than a year to actually read the Watson and Crick
(1953) paper, he quickly used the developments in
molecular genetics and the success in prebiotic syntheses to
update his gene-first proposal by arguing that what had
emerged in the primitive oceans had been, in fact, a pri-
mordial DNA molecule: it is to be expected that at last,
just before the appearance of life, the very ocean had
become, in Haldanes (1929, 1954) vivid phraseology, a
gigantic bowl of soup, wrote Muller, and added drop
into this a nucleotide chain and it should eventually
breed! (Muller 1961).
A few years later Muller stated that life as we know
it, if stripped of all its superstructures, lies in the three
faculties possessed by the gene material. These may be
defined as, firstly, the self-specification, after its own
pattern, of new material produced by it or under its
guidance; secondly, of performing this operation even
when it itself has undergone a great succession of per-
manent pattern changes which, taken in their totality, can
be of a practically unlimited diversity; thirdly, of, through
these changes, significantly and (for different cases)
diversely affecting other materials and, therewith, its own
success in genetic survival. Muller added that the gene
material alone, of all natural materials, possesses these
faculties, and it is therefore legitimate to call it living
material, the present-day representative of the first life.
(Muller 1966). In other words, for Muller (and many
others), the essence of life lies in the combination of
autocatalysis, heterocatalysis, and mutability, i.e.,
evolvability.
For Muller, who maintained his detestation of all things
Soviet and remained bitterly disillusioned by Stalins
regime and Lysenkos tragic affair, life could be so well-
defined that the exact point at which it started could be
established with the sudden appearance of the first DNA
molecule. But, DNA alone is functionally inept, and Oparin
refused to admit that life could arise all at once by a
spontaneous generation of a single catalytic and replicating
molecule stripped of all other recognized attributes of
extant life. In 1957, while the Soviet academic establish-
ment was still reeling from the all powerful structure that
Lysenko had dominated during Stalins lifetime, Oparin
wrote in his new book The Origin of Life on the Earth that
the molecule of nucleic acid in contemporary living
organisms is not an independent living molecule, it is
only a part of living protoplasm, an organ of that proto-
plasm subserving a function necessary for life (Oparin
1957).
Oparin (1957) consistently rejected the possibility of a
mechanistic explanation of the origin of life by the mere
self-assemblage of functional parts and insisted on the key
role of precellular evolution. As he wrote, it would be
wrong to suppose that there first arose proteins, nucleic
acids and the other complicated substances found in the
protoplasm, which had intramolecular structures which
were extremely well and efficiently adapted to the perfor-
mance of particular biological functions and that living
protoplasm itself arose as the result of a combination of
these substances (Oparin 1957).
The alternative to these simplistic models, wrote
Oparin, was to recognize that the conditions of the
prebiotic environment had led to the formation of
polymers in the shape of polypeptides and polynu-
cleotides, assemblages having, as yet, no orderly
arrangement of amino acid and nucleotide residues
adapted to the performance of particular functions.
These polymers were, nevertheless, able to form multi-
molecular systems, through these were undoubtedly
simpler than living protoplasm. It is only by the pro-
longed evolution of these systems, their interaction with
their environment and their natural selection that there
developed the forms of organization characteristic of the
living body: metabolism, proteins, nucleic acids and
other substances with complicated and purposeful
structures which characterize the contemporary living
organism (Oparin 1957). In other words, there was no
spontaneous origin of the exquisite structure and func-
tional properties of nucleic acids, enzymes, or metabo-
lism, but it is only through an extension of Darwinian
evolution to the subcellular components that their
emergence can be understood.
123

Conclusions
As Farley (1977) stated, Oparins (1938) book may be the
most significant work ever published on the origin of life.
This as well be true. In 1952, a year before the results of
the MillerUrey experiment and the double-helix model of
DNA were published, Lanham (1952) wrote that [i]t is
probable that Oparins contribution to the vast amount of of
organization of biochemistry that has taken place in the last
two decades will out to be a major one; in addition, his
book provides an exceptionally fine model of the applica-
tion of the historical (in the sense of evolutionary)
approach to basic biological problems, in contrast to what
has often been a purely mechanical approach.
Quite ironically, 1953 was not only the year in which the
publication of the MillerUrey experiment appeared to
validate the basic premises of the heterotrophic theory, but
also the year in which the double-helix model of DNA
marked the rise of molecular biologists, many of which at
first despised evolutionary studies and were contemptuous
of Oparins approaches (Graham 1993). The old descrip-
tions of central biological processes that came apart with the
birth of molecular biology showed few signs of putting
themselves back together, but until the very end of his long
scientific career, Oparin remained a staunch antireduction-
ist. As shown by his last essay, [O]ne must clearly
imagine that there were no polynucleotides capable of
replication or polypeptides having some specificity in their
sequence under the influence of these polynucleotides
which entered the selective process but rather as a whole
system. In this same text, Oparin reiterated the non-
teleological argument implicit in his idea of what he had
termed pre-natural selection, which is the attempt to Bernal JD (1967) The origin of life. Weidenfeld and Nicolson,
extend Darwinian evolution to the non-living chemical
systems from which the structure and function of subcellular
components evolved (Oparin 1972). As he added, [In the
primitive soup]both the complex order of chemical
reactions characteristic of biological metabolism and any
kind of biological structure were absent. In particular, even
though they possess certain intramolecular organization and
catalytic action, the protein-like polymers of the primor-
dial soup are principally different from protein of present-
day organisms. The structure and the enzymatic action of
the latter are found everywhere completely adapted to per-
form the function which they carry out in living entities.
Such adaptiveness or purposiveness, of organization Goldschmidt R (1917) A further contribution to the theory of sex.
even at the molecular level, was certainly absent from the
simple aqueous solution of chemical compounds. This
purposiveness could only arise during the process of the
origin of life, at the transition from chemical to biological
evolution, on the basis of the formation and natural selection
of integral prebiological systems (Oparin 1972).
123
J Mol Evol
Eighty years after Oparins second book was published,
it has become clear that the open character of his theory of
chemical evolution and of a heterotrophic origin of life has
allowed the incorporation of new discoveries and the
development of more accurate descriptions of possible
primitive scenarios without destroying its overall structure
and premises. The heterotrophic theory is not chiefly about
a highly reducing primitive atmosphere or about coacer-
vates, but about the gradual, but not necessarily slow, of a
number of changes brought about by the emergence of
more complex structures and processes during prebiotic
evolution. The current schemes are not without difficulties,
and there are of course massive blind spots. However, by
placing the origin of life well within a Darwinian per-
spective, Oparin transformed the study of the origin of life
as from a purely speculative questions into an evolutionary
issue, thus providing a framework into which a large
number of observations and experiments ranking from
astrophysical phenomena to microbial metabolisms can be
studied.
Acknowledgements Support from project UNAM-PAPIIT
IN223916 is gratefully acknowledged. I thank Sara Islas, Ricardo
Hernandez-Morales, and Alberto Vazquez Salazar for the help with
the manuscript.
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