Journal of Genetics © Indian Academy of Sciences

DOI 10.1007/s12041-017-0831-6

HALDANE AT 125

J. B. S. Haldane and the origin of life

STÉPHANE TIRARD∗

François Viète Center for Epistemology and History of Science and Technology, University of Nantes, Nantes, France
∗ E-mail: [email protected].

Abstract. In 1929 the British biologist John Burdon Sanderson Haldane published a hypothesis on the origin of life on earth,
which was one of the most emblematic of the interwar period. It was a scenario describing the progressive evolution of matter on
the primitive earth and the emergence of life. Firstly, this paper presents the main ideas put forward by Haldane in this famous text.
The second part makes comparisons between Haldane and Alexander Ivanovitch Oparin’s ideas regarding the origins of life (1924).
These two theories, apparently very similar, presented distinct conclusions. The third part focusses on Haldane’s reflections on the
emergence of life during the 1950s and 1960s, and shows how they were linked to the recent developments of prebiotic chemistry and
molecular biology.

Keywords. origin of life; Haldane; Oparin; prebiotic chemistry; RNA world.

Introduction The first part of this paper reviews the main ideas put
forward in Haldane’s famous paper, which had a great
During the second part of the 19th century, the issue of the impact on the history of ideas on the origin of life. Accord-
origin of life was renewed by the emergence of evolutionary ing to the British biologist, life was able to emerge on
theory, on the one hand, and by the refutation of sponta- earth through a progressive chemical evolutionary process,
neous generation theory, particularly after Louis Pasteur’s which he described by means of a very clear and concise
experiments, on the other hand. Two solutions were pro- scenario.
posed to this issue: the first regarded the possibility of the The second part of this paper makes comparisons
progressive evolution of matter on the primitive earth, and between Haldane and Oparin’s ideas regarding the origins
the second concerned the panspermia theory claimed, for of life (1924). For several reasons, their papers are often
instance, by William Thomson (1872) or Svante Arrhenius associated in the Oparin–Haldane hypothesis. It is impor-
(1908) (Fry 2000; Tirard 2006). Panspermia was largely tant to compare them to understand the reason behind this
abandoned at the end of the 1910s (Tirard 2013). In the association, as well as to underline the important concep-
1970s, it was rarely used (Crick and Orgel 1973; Hoyle and tual distinctions between them.
Wicramasinghe 1979) as an assumption made to under- The third and last part focusses on Haldane’s reflections
line and discuss the improbability of the emergence of life on the emergence of life during the 1950s and 1960s. Hal-
and was not shared by the community of specialist on the dane’s return to this issue in several papers showed his great
origins of life (Dick 1996; Fry 2000). Therefore, during the interest in it and confirmed the originality of his thought.
interwar years, the several important hypotheses put forth
were evolutionary. John Burdon Sanderson Haldane pub-
lished one of the most emblematic hypotheses in 1929. In 1929: A scenario of the origin of life on the earth
a short text, he brilliantly associated his reflection on the
nature of life with a scenario of the origin of life on the Haldane’s first contribution to the origin of life was pub-
earth (Haldane 1929). (For an overview of the history of lished in The Rationalist Annual in 1929. When Haldane
the theories on the origin of life see Dick (1996), Farley wrote it, he occupied two positions. Since 1923, he was a
(1997), Fry (2000), Kamminga (1991) and Tirard (2010)). reader in biochemistry at Cambridge and, starting with
 Stéphane Tirard

1927, he also had a position at the John Innes Horticul- possibility of an intermediate state: ‘The first living or half
tural Institution (Clark 1972). At the end of the 1920s, living things were probably large molecules synthesized
he was a well-known scientist, excelling in physiology, under the influence of the Sun’s radiation, and only capable
biochemistry, enzymology, genetics, and the evolutionary of reproduction in the particularly favourable medium in
theory. His paper from 1929 undoubtedly benefited from which they originated. Each presumably required a variety
his impressive knowledge. It is often considered as one of of highly specialized molecules before it could reproduce
the first synthetic papers on this topic and it constitutes itself, and it depended of chance for a supply of them.’
a milestone in the history of ideas on the origin of life. It Then he continued with the emergence of a cell: ‘The cell
has the double characteristic of being addressed to a large consists of numerous half-living chemical molecules sus-
public and presenting original views. It is notably for these pended in water and enclosed in an oily film. When the
two reasons that it was recorded for posterity. whole sea was a vast chemical laboratory the conditions
To introduce the issue, Haldane first drew attention to for the formation of such films must have been relatively
the fact that, even if the old idea of spontaneous generation favourable; but for all that life may have remained in the
had been abandoned in the 19th century, it was still possi- virus stage for many millions of years before a suitable
ble to accept that such an evolutionary process occurred in assemblage of elementary units was brought together in
the past. Second, he questioned the possibility of viruses the first cell. There must have been many failures, but the
being alive. He was indeed very interested in the debate first successful cell had plenty of food, and an immense
on this issue. At that moment, viruses were only known as advantage over its competitors.’
agents of infectious diseases. They were invisible and had These previous quotations show how Haldane orga-
the property of being able to pass through the tiniest filter nized a hypothesis on the origin of life constituted by
used in microbiology laboratories. In his paper, Haldane three main stages depending on the conditions of the prim-
focussed on d’Herelle and Bordet’s opposing views. The itive earth. Firstly, organic molecules were synthesized
former, who discovered bacteriophages, which infect bac- under the action of ultra-violet light on primordial mixture
teria, claimed that these viruses were living organisms. The of water, carbon dioxide, and ammonia. Secondly, under
latter believed them to be a ferment. Haldane preferred the action of the sun’s radiation on this hot dilute soup,
to follow the intermediate view of the American geneti- large molecules capable to reproduce themselves emerged.
cist Muller (1926), who compared ‘the bacteriophage to a Thirdly, cells were formed.
gene—that is to say, one of the units concerned in heredity’
(Haldane 1929). Finally, Haldane claimed that ‘The bac-
teriophage is a step beyond the enzyme on the road to life, Oparin and Haldane: two parallel ways
but it is perhaps an exaggeration to call it fully alive’ (Hal-
dane 1929). Undoubtedly, his reflection on viruses was very Oparin and Haldane are very often associated in histori-
heuristic in terms of the issue of the limits of life (Podolsky ography and their hypotheses are evaluated as very similar.
1996) and particularly of the origin of life. This can be explained by a variety of reasons. Firstly,
Regarding the scenario of the origin of life on the earth, their publications were quasi simultaneous. Haldane’s text
Haldane began his description after the cooling of the came five years after Oparin’s (Oparin 1924). However,
earth, when it developed a solid crust and when water was it is important to note that he did not know about the
condensed. He insisted on the primitive conditions and, Soviet scientist when he wrote his own paper. Therefore, it
according to him: ‘The primitive atmosphere contained is an interesting case of simultaneity, which amplified their
little or no oxygen and was rich in carbon dioxide (…). common posterity. Secondly, their two texts described,
The sun was perhaps slightly brighter than it is now, and step-by-step, using a very similar method, the progressive
as there was no oxygen in the atmosphere the chemically emergence of life on the primitive earth. Thirdly, the pos-
active ultraviolet rays…’ sible influence of Marxist ideas on Haldane and Oparin
His assumption could be considered as a phototrophic was often discussed (Graham 1973; Gouz 2012; Lazcano
pathway of synthesis of organic molecules. He claimed 2016). It is important to underline that, in their first texts
that: ‘when ultra-violet light acts on a mixture of water, on the origin of life, there was no reference to Marxism
carbon dioxide, and ammonia, a vast variety of organic or to political influences. At that time, Haldane had polit-
substances are made, including sugars and apparently ical ideas which were more to the left, but he had not yet
some of the materials from which proteins are built up’. joined the Communist Party; he did it at the beginning
He added that: ‘before the origin of life such substances of the Spanish war. It seems possible to claim that Hal-
must have accumulated till the primitive oceans reached dane wrote this text without any political or philosophical
the consistency of hot dilute soup’. This metaphor of the influences other than simple materialism. When it comes to
‘soup’, invented by Haldane, was continuously and widely Oparin, it also appears that, at the beginning of the 1920s,
used in literature. It certainly contributed to the posterity he was motivated by his own interest in evolution and that
of this text. Haldane continued with the explanation of his Marxist ideology did not appear in his work. Fourthly, a
conception of the first living things, and insisted on the last common point must be underlined even if it is rarely
 J. B. S. Haldane and the origin of life

signalled. Both Oparin and Haldane insisted on the histor- actively pursued the field of the origin of life throughout
ical character of the process of the origin of life, which was his career. He published an important book in 1936, which
unique in the past and did not leave any geological traces. was translated into English in 1938 with the title The ori-
In this regard, they noticed the particular position of sci- gin of life, and, as biochemist, he became the leader of the
entists when confronted with such a problem and Haldane Soviet school of the origin of life. After the WWII, Oparin
did not hesitate to write: ‘The biochemist knows no more, devoted his career to the origin of life. In the Soviet context
and no less, about this question than anyone else. His igno- led by Lysenko, he was constrained to neglect the develop-
rance disqualifies him no more than the historian or the ment and consequences of molecular biology and partic-
geologist from attempting to solve a historical problem’ ularly the roles of nucleic acids. However, despite the Cold
(Haldane 1929). War, Oparin stayed in contact with Western specialists on
However, beyond the common characteristics of their the origin of life and focussed his own work and that of his
models, some differences existed in their respective con- school on the metabolic and energetic aspects of the issue.
ceptions of primitive life. Oparin’s paper, which was longer
than Haldane’s, insisted more on the formation of the The extensions of Haldane’s thought on the origin of
earth. However, they agreed on the absence of O2 and the life
presence of CO2 in the primitive atmosphere. According
to them, the first organic synthesis occurred in the prim- During the 1950s, Haldane returned to the issue of the
itive atmosphere and continued in seawater. However, an origin of life in several papers, in which he revisited his
important difference existed regarding the final products own views and those of his colleagues. Pirie illustrated very
imagined by the two scientists. According to Oparin, the well how Haldane was able to connect the more up-to-date
organic compounds aggregated, producing some little ‘bits scientific thought (Pirie 1968). This was undoubtedly the
of gel’, which prefigured the primitive cells. Oparin always case in the 1950’s.
focussed on metabolism and, starting in 1936, he used He was very stimulated by the recent changes occurring
coacervates which, according to him, ‘may be compared in the scientific context. Firstly, the 1950s stood out as
to the properties of protoplasm’. He claimed that ‘the the beginning of a new period for the study of the origin
coazervate represents a special type of concentrated col- of life, with the first experiments of prebiotic chemistry.
loidal sol, in which the water molecules are rigidly oriented This method was used to study possible chemical path-
with regards to the colloidal particle. A real separation is ways in experimental conditions respecting the supposed
thus brought about between the shell of oriented water conditions of the primitive earth. Calvin inaugurated this
molecules and the free molecules of the equilibrium liq- direction in 1951. He exposed CO2 in solution to gamma
uid’ (Oparin 1938). rays and obtained formic acid (Garrisson et al. 1951). Two
In contrast, the successive hypotheses proposed by Hal- years later, Stanley Miller tested a hypothesis suggested by
dane in 1929 focussed increasingly on molecules respon- Harold Urey. In a famous experiment, he exposed a mix-
sible for heredity. Contrary to Oparin, Haldane followed ture of CH4 , NH3 , H2 O and H2 to electric discharges for
the same lines as Muller who claimed, in 1926, that the one week, showing the production of amino acids (glycine,
gene was the basis of life (Muller 1926; Fry 2000; Falk α-alanine and β-alanine) (Urey 1952; Miller 1953). There-
and Lazcano 2012). He notably referred to genes when fore, these two experiments were emblematic of a new and
he focussed on the issue of the growth and reproduction very active field with chemical investigations and scien-
of large molecules, claiming: ‘They occur, it would seem, tific debates on the origin of life (Ponnamperuma and
in certain polymerizations which are familiar to organic Gabel 1968). Secondly, the 1950’s were remarkable due to
chemists. In my opinion the genes in nuclei of cells still the development of molecular biology, which revealed the
double themselves in this way. The most familiar analogy roles of nucleic acids and their relationship with proteins.
to the process is crystallization.’ Therefore, it was in this new context, characterized by
It is necessary to also underline the differences regard- the double emergence of prebiotic chemistry and molecu-
ing the issue of the primitive metabolism. The progressive lar biology, that Haldane confirmed his interest in global
complexity of organic matter described by Oparin argued reflections on the origin of life. His claim from 1929 regard-
for a heterotrophic process. Haldane, taking a contrary ing half-living molecules found a new meaning in this new
stance, as seen above, insisted on the role of light in chem- conceptual context, due to the fact that molecules were
ical synthesis, and preferred an autotrophic process. now identifiable with nucleic acids. Contrary to Oparin,
The last point to be underlined regards the place of he clearly adopted the new concepts of molecular biology.
the origin of life in their respective careers. As mentioned His main lines of vision on the origin of life stayed the
above, Haldane was already an accomplished scientist in same as in 1929, with a progressive evolution of matter
1929, with a large panel of specialities. Thereafter, the ori- from molecules to cell (Haldane 1954, 1957). However,
gin of life was only one among his many subjects of study, it referred to recent biochemical data. It was based on a
and he returned to this topic only in the 1950s. In con- first stage of simultaneous syntheses of three fundamental
trast, Oparin, who first specialized in plant physiology, categories of complex organic molecules: polysaccharides,
 Stéphane Tirard

proteins and nucleic acids, which were capable of replica- tion of a biologically relevant RNA pattern might be very
tion. Then he imagined that a monolayer of protein could greatly increased, without any supposition that a vital force
enclose some of these molecules. However, he changed his or soul was guiding the molecules into the right configu-
mind on primitive atmosphere and claimed that it con- ration’ (Haldane 1965).
tained methane rather that CO2 .
Haldane completed his hypotheses nourished by new
concepts on molecular biology and biochemistry. How- Conclusion
ever, his work on the emergence of life appeared to be
closely linked to his reflection on minimal life. The follow- Haldane is often presented, together with Oparin, as the
ing quote is a perfect illustration of his approach: ‘I believe author of one most important hypotheses of the mid-war
that life demands not only self-reproducing molecules but period on the origin of life. Throughout his life, he main-
a self-reproducing system of such molecules’ (Haldane tained an interest in this issue and, more generally, in
1957). Beyond this first principle, he claimed: ‘The min- fundamental issues such as nature and the definition of
imum living organism which I can imagine would contain minimal living organism.
a copyable nucleic acid spiral, whose structure enabled it to He was also able to participate in the renewing of the
make at least the following enzymes’ (Haldane 1957). He reflection on origin of life during the 1950s and 1960s and
provided a list: a nuclease, a proteinase, phosphokinases, a incorporated the newest data of molecular biology in his
nucleosidase. He added that ‘It would also contain a supply own original approach. His last contribution to the issue
of a self-reproducing pyrophosphoric ester, possible ATP. was the very interesting assumption that RNA was impor-
Such a system would automatically synthesise adenosine. tant at the origin of life.
It would be surrounded by a monolayer of protein, possi-
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