J. theor. Biol.

(1997) 187, 583–593

Biogenesis Itself
T G́

Hungarian Academy of Sciences, Ecological Modelling Research Group, Cogitator, H-2626

Nagymaros, Rákóczi, u. 46, Hungary

(Received on 29 March 1996, Accepted on 26 April 1996)

In the biological sense, biogenesis is the spontaneous assembly of program-controlled, self-reproducing

fluid automata under prebiotic conditions. In order to understand this phenomenon, principles of the
theory of fluid automata should be laid down, as well as those of cycle stoichiometry which makes the
exact, quantitative design of such chemically organised fluid automata possible. In addition, we need
a minimum model of programme-controlled, self-reproducing fluid automata, the so-called chemoton
model. All this together ensures the possibility of studying biogenesis under the conditions assumed
correct.
7 1997 Academic Press Limited

Objective Interpretation of Some Concepts

In the general evolutionary sense, biogenesis is a Hard machineries (such as mechanical automata,
long process, as it includes the formation of electric or electronic instruments) are built of solid
conditions on the surface of a given planet needed parts and the arrangement of these parts corresponds
for the origin of life, the spontaneous formation to a well-defined geometrical order. This geometrical
and accumulation of chemical compounds necessary order is characteristic of the function of the given
for the development and functioning of most machinery, destroying this order results in the loss of
simple living systems, the development of the the specific function.
specific parts or subsystems of living organisms Fluid machineries, on the contrary, do not contain
(such as macromolecules, membranes, autocatalytic any solid part, and though their parts are connected
cycles, etc.), together with the ensurance of in accordance to a strictly determined order, this
the formation and continuous recycling of raw order is not a geometrical one. In our case, the fluid
materials needed for the continuous operation of machineries are chemical machineries, their elements
living systems. are dissolved chemical compounds, and the order
In the biological sense, biogenesis is a very short ensuring their functions is a chemical organisation,
process, as it includes the assembly of fluid that is, a reaction network. For example, the
machineries possessing the ability of hereditary well-known oscillatory chemical systems do not have
variability appearing at self-reproduction and serial any geometrical structure, shown by the fact that they
self-reproduction processes. keep on oscillating undisturbed even when stirred.
In the physiological sense, biogenesis might Nevertheless, they should have some machine-like
even mean an instantaneous event, if it concerns structure to show such a regularly changing,
the moment when the viable system starts to oscillatory behaviour. Actually they do have such an
operate. internal structure: the order in which the various
The objective of this paper is to interpret chemical reactions proceed in the oscillatory reaction
biogenesis in the second, biological sense, i.e. mixture are connected to each other. This structure
the spontaneous assembly of fluid machineries can be conveniently visualised as a chemical reaction
possessing the ability of self-reproduction and genetic network, its functioning can be predicted in an exact
variability. way by means of chemical kinetics. (The fact that this

0022–5193/97/160583 + 12 $25.00/0/jt960391 7 1997 Academic Press Limited

584 . ́

invisible chemical organisation can be converted into parts, whereas the latter only as a whole (Leibniz,
geometrical structures in certain cases, for which just 1705, 1710, 1714). References to similar thoughts also
oscillatory reactions serve as spectacular examples is appear in the works of Bertalanffy and Schrödinger
another matter.) (Bertalanffy, 1952, Schrödinger, 1944).
In spite of the fact that in these reaction systems Actually only the simplest living systems, my-
each elementary step can be described exactly with coplasms and thermoplasms can be regarded as pure
stoichiometric equations, for the description of the fluid automata; in an early phase of evolution
chemical organisation of the system, usual chemical semi-hard (cell organella) and hard (cell walls)
equations are not applicable. The reason for this is elements appeared in living beings. Through these,
that the loops of chemical feedbacks, the members of geometrical organisation was discovered, which now
cycles and networks are eliminated in the overall plays a decisive role in the majority of the living
equation, as—due to their cyclic operation—they world. Thus, the majority of living beings are
appear at both sides of the overall equation, i.e. they regarded as soft automata, in which fluid and
are, at the same time, both, raw materials and geometrical organisation are present simultaneously.
products. This is why chemical stoichiometry is In soft automata, the basic function is fulfilled by fluid
unable to include catalysis—for example the oper- organisation (metabolism), the submicroscopic results
ation of enzymes—in its equations. of which are transformed into mechanical or electric
Cyclic stoichiometry (Gánti, 1976a) was born to processes at a microscopic or macroscopic level.
solve this problem. This makes the exact, quantitative Thus, the understanding of biogenesis in the
interpretation of chemical feedbacks and cycles, even evolutionary sense requires the clarification of
that of self-reproducing (autocatalytic) processes whether fluid machineries could be formed spon-
(Gánti, 1976b) possible. taneously, moreover, whether self-reproducing sys-
For fluid automata, namely, the realisation of tems could be developed on the surface of the
self-reproduction is possible. In the case of hard primordial Earth. From the biological viewpoint, if
automata, self-reproduction of parts is impossible due such systems can spring into existence, one needs to
to geometrical restrictions. No such limitation exists study whether their spontaneous coupling could lead
for fluid automata—see autocatalytic reaction sys- to the development of fluid supersystems that could
tems—, thus self-reproduction is realistic. It is also be regarded as living systems. The fluid structural
possible that self-reproducing fluid automata (chemi- conditions of this coupling also needs to be clarified.
cal supersystems) are formed, from self-reproducing The first thing that needs to be decided for all these
parts, i.e. from various autocatalytic reaction systems. problems to be reasonable is what can be considered
There is also a theoretical possibility for the living.
formation of chemical supersystems in which simple
chemical self-reproduction is combined with spatial
division (Gánti, 1975, 1978a). Cycle stoichiometry is Life Itself
capable of handling the organisation of these systems The extent of which this subject has decreased from
quantitatively as well (Gánti, 1978a, 1979a). the focus of todays scientific interests is notable. In
All this led to the elaboration of the general theory the last decades, practically only Varela has been
of fluid automata (Gánti, 1984). By means of this, examining this problem (Varela, 1979, 1994; Varella
fluid automata can be designed and dimensioned as et al., 1974). It is most interesting, as the question:
mechanic engineers or electric engineers design their ‘‘what is the essence of life?’’ is not only the basic
hard (mechanical, electric) machines and instruments. problem in biology as a science, and is not only an
Fluid automata designed this way have already found inevitable condition for the interpretation of the
industrial application in producing fine chemicals biogenetic process, but it is also indispensable in the
(Gánti, et al. 1970; Gánti & Csóka, 1973, 1975). ethical and legal clearing up of social-religious
Living systems are also fluid automata as to their conflicts such as the problem of abortion, organ
basic functions, since their energy manipulating, mass transplantation or euthanisia. Thus, studies on the
transforming, even regulating and programme- merits concerning the real nature of life originate
control processes proceed in solutions, i.e. in the fluid from times when there was not an exact answer to this
state. This was first recognised by Leibniz, who question due to the lack of appropriate scientific
emphasised in several of his works that natural or (mainly molecular biological) knowledge (Leibniz,
divine automata—that is, living beings—are distin- 1705, 1710, 1714; Schrödinger, 1944; Bertalanffy,
guished basically from manmade machines by the fact 1995; Bauer, 1935). Works incorporating the results
that the former are automata down to their smallest of molecular biology did not receive enough publicity
   585

due to the lack of interest in the field (Gánti, 1971, type. They constitute a supersystem through the
1977, 1989). stoichiometric connection between them, thus they
The result from the viewpoint of biogenesis is total are unable to function without each other. Moreover,
chaos. For example, Sydney Fox considers his the membrane encloses the whole supersystem, which
proteinoid microspheres living (Fox, 1964, 1965, thereby forms a spatial unit. It can be proven that,
1973) without providing the criteria for life. The case even in its most primitive form, this compartmen-
is similar with Bahadur and his formations called talised supersystem divides into two identical
Jeewanu. His works are disdained because of the compartments when the amount of its internal
simple technical methods applied, though it could not materials is duplicated, as a result of mere
be excluded that in his experiments living systems physico-chemical conditions (Gánti, 1975; Gánti &
were present (Bahadur, 1966, 1967; Bahadur & Gáspár, 1978; Verhás, 1989), that is, it is capable of
Rangayanaki, 1970, 1983). The situation was proliferation by fission. The model can be decom-
somewhat similar in the works of Clair Folsome posed to its elementary chemical steps; its chemical
(Folsome, 1976, 1977; Folsome & Brittain, 1981), processes can be calculated by means of cyclic
who used up-to-date methods but never stated that stoichiometry.
his formations were alive although it could not be The author considers the chemoton model not as
excluded that the objects which appeared in his an intermediate station of biogenesis, but as the basic
experiments could be considered living. All these model of living systems. This statement can be proven
experiments can be regarded as alchemistic (not in the from two different points of view. On the one hand,
pejorative sense of the word), since the results were it is possible to investigate whether the organisation
born as a consequence of complex, confused effects of a chemoton is present in living systems. On the
caused by the given external conditions without the other hand, the exact nature of the model allows us
exact knowledge of the elementary processes in- to determine the reaction kinetic equations of the
cluded. elementary steps (Békés, 1975; Gánti, 1984). The
Two of the theoretical models tried to cross the behaviour of the given chemoton under various
border between living and non-living things: the internal-external conditions can be calculated factu-
hypercycle model (Eigen, 1971; Eigen & Schuster, ally by the numerical solution of the differential
1979) and the chemoton model (Gánti, 1971, 1975, equation system obtained (Békés, 1975; Csendes,
1978a). The common key is that both are fluid 1984). The results should then be checked to see
automaton models and both are chemical supersys- whether they predict a behaviour similar to that
tems constructed from autocatalytic chemical sys- expected from living beings, i.e. whether chemotons
tems. (It is an interesting fact that both were fulfil the criteria of living systems.
published almost on the same day, at the beginning There is now evidence that a chemoton-type
of October 1971). However, there are also some organisation is present in living beings, although at
fundamental differences between them. In the the birth of the model this was not so. Every cell,
hypercycle (at least in the original variant, because without exception, possesses a metabolic network
later various interpretations were also published) the transforming external nutrients into its own internal
autocatalytic subsystems consist of RNA or RNA- materials, ensuring thereby the energy provision of
like macromolecules together with RNA-polymerase- the cell. Every living cell has a genetic apparatus
type macromolecules of enzyme functions. The reproducing itself in a template process and governing
hypercycle itself is not separated from its environment the operation of the whole supersystem. Every living
(compartmentalisation problem) and in addition, the cell is surrounded by a cell membrane, which
model is not capable to evolve in that direction. Its selectively transfers materials between the internal
functioning essentially outlines an imaginary evol- and external space. Moreover, in every cell, again
ution path of informational operations. Eigen does without exception, the metabolic network produces
not say that the hypercycle is the model of a living the materials necessary for replication of templates
system, but he supposes that biogenesis is realisable and growth of the membrane. In fact the chemoton
through hypercyclic systems. model is just the representation of fluid organisation
Unlike the hypercycle, three different autocatalytic by a reaction network (expediently in a form
cycles are coupled to form a chemical supersystem in simplified to the utmost), and the quantitative
the chemoton model. One of them is an autocatalytic description of this chemical supersystem by means of
reaction network consisting of small molecules, the cycle stoichiometry.
second is a template polymerisation system, and the However, to obtain proof of the living nature of
third is a membrane-growing system of autocatalytic the system is not so simple, because it necessitates a
586 . ́

criterion or criterion system, on the basis of which it (6) During their continuous proliferation, could the
can unambiguously decide whether a system is living chemical supersystems have suffered serial genetic
or not (life criteria). Such a generally accepted system changes, leading finally to the development of the
of criteria does not exist in biology. Therefore, present living world?
simultaneous with the development of the chemoton
model, a new system of life criteria, broader and The first two questions will not be dealt with in this
stricter than any other already existing which also study, partly because they belong to the field of
takes into account the results of up-to-date biology, chemical evolution and partly because since the
has been developed (Gánti, 1971) and further refined classical experiments of Miller (1953), thousands of
(Gánti 1977, 1978b, 1989). If we accept this system of publications have proven that the answer is yes. The
criteria for distinguishing between living and non-liv- last two questions will not be dealt with, because they
ing systems, then systems possessing the organisation are beyond the scope of this paper. However, a
of a chemoton have to be considered living systems on ‘‘positive’’ answer is also probable for these; a
the basis of both the logical thinking over their detailed discussion of this subject is to be found in the
operation and the results of computer simulations. monograph of the author treating this question
Concerning the chemoton model it should be (Gánti, 1989).
emphasised that it is the basic model of fluid Thus, the third and fourth questions will be dealt
organisation, i.e. it provides the chemical-stoichio- with in what follows. That is, the possibilities of the
metrical connections from which the specific proper- formation of the three subsystems of a chemoton, the
ties of the system originate. Thus, its validity is prebiotic development of a connection between them,
independent of the question of whether its elementary and their coupling into a chemical supersystem of
steps take place according to the laws of mass action chemoton organisation will be discussed. The
alone, or if they are catalytically accelerated, or even ‘‘subsystems’’ themselves are, also chemical systems,
whether this catalytic process itself is subjected to which can even be very complex themselves, but
regulations, as occuring like those in the present living within the chemoton as a system, they operate as
world through enzyme regulation. subsystems.
Another point to be emphasised is that the usual It should be noted here that, although the
representation of the chemoton model is expediently chemoton model contains strict restraints for the
an oversimplified form containing only the stoichio- coupling of the reactions and for the stoichiometric
metric key steps of the system (Fig. 1). Its cycles can relations, no requirements are included for the
be substituted by networks of arbitrary complexity, if concrete nature or the composition of its chemical
they are autocatalytic and satisfy the stoichiometric components. If, for example, reaction systems of
requirements of the key steps. chemoton organisation could be constituted from
In the possession of such a quantitative model, the silicon-based compounds, they would also behave as
general question of how life was born, can be divided living systems. However, to our present knowledge,
into partial questions which can be answered the formation of such reaction networks is only
scientifically, and even experimentally. These ques- probable for carbon compounds.
tions follow. Thus, for clarifying the process of biogenesis, at
least the spontaneous, abiotic formation of three
(1) Under the prebiotic conditions on Earth, was it different, stoichiometrically connectible reaction sys-
possible that compounds suitable for coupling into tems consisting of organic compounds should be
autocatalytic reaction systems were formed? proved. One of them is the metabolic subsystem, the
(2) Could autocatalytic systems be formed and second one is an information subsystem operating by
operate successfully? template polymerisation, whereas the third one is a
(3) Were there systems among them which corre- two-dimensional, fluid membrane layer capable of
sponded to the criteria related to the different autocatalytic proliferation.
subsystems of the chemoton?
(4) Could these systems be coupled to supersystems
of chemoton organisation? The Metabolic Subsystem
(5) Was there a continuous provision of raw material The metabolic subsystem is the motor of the whole
for the large-scale proliferation of chemical supersys- supersystem. Its task is to transform raw materials so
tems with chemoton orgnisation, i.e. could cycles of that the internal materials of its own network are
material transformations be formed which continu- doubled between two divisions, producing meanwhile
ously regenerated the raw materials consumed? the materials needed for the self-reproduction of the
   587

T
m
+k

A2
X Y

A1
A1 A3
R

pV n V 1

A5 A4 V'

pV n pV n V n
pV n

T'

T"

Tm
1
Tm+

Tm

F. 1. The minimum model of chemotons. Three self-producing subsystems coupled stoichiometrically: Cycle A : 2A, template
polycondensation pVn : 2pVn and membrane formation Tm : 2Tm . This coupling results in a proliferating, programme-controlled fluid
automaton, known as a chemoton.

other two subsystems or their precursors. In the chemoton. However, it has not actually been
minimum chemoton model this is represented by a investigated until now: no ‘‘metabolic map’’ of any
five-step autocatalytic cycle. One of these steps stands cell type is known at present in its whole complexity
for the introduction of nutrients into the system, one and concreteness.
for waste material formation, two for the formation Although the metabolic subsystem of living cells
of the raw materials of the two other subsystems, and consists of several hundreds of reaction steps, in every
finally one for an autocatalytic process, i.e., the living cell it fulfills the requirements of the minimum
production of an internal compound of the cycle. This chemoton model: it produces raw materials or
is much more complex in actual living cells—the core precursors for the reproduction of its own material
of the metabolic system, which consists mainly of and that of the other two subsystems by utilising
reaction networks of organic acids and carbo- nutrients and producing waste materials. The
hydrates, is represented by this single reaction in the existence, nature and connections of reaction
588 . ́

networks operating under prebiotic conditions have atmosphere by means of light, thus, the formose
hardly been investigated experimentally, however, reaction principally possesses the properties required
from the fact that the formation of small organic for the metabolic subsystem of the chemoton
molecules has been detected in chemical evolution model.
experiments, it follows unambiguously that such Although it was previously a general conviction
reaction networks necessarily have been operating that the primordial atmosphere was a reducing one,
under primordial conditions. in the last decades there had been an increased
The first concrete reaction network supposed to be opinion that it was neutral or weakly oxidising. In this
operating under prebiotic conditions is the reaction case, the abiotic formation and accumulation of
system called formose reaction. The reaction was organic compounds is not so evident as in the
discovered by Butlerow in 1861, its autocatalytic case of a reducing atmosphere. Therefore, reaction
nature was recognised by Neuberg in 1902, whereas systems capable of carbon-dioxide fixation, and thus
the main steps of the reaction system were elaborated of its utilisation as raw material, were investigated.
by Langenbeck in 1942. Its prebiotic significance was Such reaction systems are known in the living world.
emphasised mostly by Decker in his numerous works First of all, the Calvin cycle should be mentioned,
(Decker, 1973, 1974, 1978; Decker & Speidel, 1972; which is a very complicated autocatalytic reaction
Decker & Heidmann, 1978). However, this prebiotic network when decomposed to its elementary steps.
role was also recognised in parallel by other authors Related to it is the so-called C4-pathway, which is an
(Cairn-Smith & Walker, 1974; Cairn-Smith et al., alternative path in certain bacteria and plants.
1972; Gánti, 1978b; Quayle & Ferenci, 1978; Degani No experimental results concerning the abiotic
& Halmann, 1967, 1971; Gabel & Ponnanperuma, operation of these carbon-dioxide fixing reaction
1967; Reid & Orgel, 1967). In spite of all this, systems are available. These reaction pathways are
knowledge concerning the kinetics and mechanism of also suitable for the production of stoichiometric
the formose reaction does not originate from chemical coupling in nucleic acid and membrane synthesis.
evolution experiments (Mizuno et al., 1970, 1971, Thus, they are also suitable for playing the role of a
1972; Mizuno & Weiss, 1974). metabolic network in a supersystem of chemoton
The first step of the reaction system is an organisation.
aldol-condensation: from two formaldehyde mol- It appears, mainly in certain prokaryotes, that
ecules one glycolaldehyde molecule is formed in a carbon-dioxide fixation is related to organic acids
very slow step. Further steps are also based on rather than to sugars. This way is the so-called
aldol-condensation and intramolecular transform- reducing citric acid cycle, which is essentially a citric
ations; however, these steps are very rapid. Thus, in acid cycle operating in the opposite direction, and
the process, glyceraldehyde, 1-3 dihydroxy-2 also being autocatalytic. Wächtershäuser discusses in
propanone, then aldoses and ketoses of 4–6 carbon several of his works the possibility of the operation of
atoms and ketoses of 7–8 carbon atoms are also an archaic variation of the reducing citric acid
formed. The reaction proceeds either in a basic media, cycle under abiotic conditions, where part of the
or in the presence of catalysts (carbonate apatite, OH-groups are substituted by SH-groups, and part
aluminium oxide). of the carbonyl-groups by their thio-derivatives
As formaldehyde is one of the most abundant (Wächtershäuser, 1990, 1992). At present it is not yet
organic molecules in the Universe, and it can also be clear, how such a reaction network consisting of
formed by photochemical reactions in the atmos- carboxylic acids can be coupled to a prebiotic nucleic
phere, it can be assumed that it has played a acid and/or membrane synthesis. It is also a problem
fundamental role in the genesis of life. This that, according to the assumption of Wächtershäuser,
assumption is supported by the fact that, among the operation of the cycle necessitates the surface of
its intermediates, certain glycerine derivatives can pyrite. Thus, in the form proposed by him, it could
be found in the formose reaction cycle, which hardly operate within compartmentalised self-repro-
make a stoichiometric coupling possible in the ducing chemical supersystems.
direction of membrane formation. Pentoses, needed All this indicates that under primordial conditions,
for the information subsystem, also appear in the depending on their nature, more possibilities prob-
reaction mixture, thus making a stoichiometric ably existed for the formation of autocatalytic
coupling towards nucleotide template polymerisation reaction networks corresponding to the metabolic
possible. In addition, the raw material of the subsystem of the chemoton. No concrete proof exists
formose reaction is continuously reformed from for this yet, since no experiments have previously been
methane and water in the reducing prebiotic performed in this direction.
   589

The Information Subsystem them. It can be proven that this process leads to the
The role of information subsystem is played in the development of sequence-dependent functions, e.g., in
chemoton model by a polymer molecule possessing the case of ribonucleic acids (Gánti 1974, 1979b,
template properties, on which the new information- 1983). Thus, the problem is further simplified, since
carrying strands are built as copies of the template. At one should not look for a random evolution of sign
first, the model does not differentiate whether the sequences independent of certain functions in
‘‘primordial soup’’, but a mechanism suitable for the
template is formed by polymerisation or polyconden-
programme-control of the given self-reproducing
sation steps; whether it is homopolymeric or is built
chemical supersystem, through the simplest possible
of different building units; whether the template
realisation. This can be sought for most expediently
process proceeds by homologeous or complementary
in the field of abiogenic template polymerisation of
pair building. It does not contain, naturally, any
ribonucleic acids.
restriction concerning the nature of the template
The possibility of non-enzymatic template polym-
either, i.e. if it is a nucleic acid, whether it is a
erisation was first proven in 1968 by several
ribonucleic acid or a deoxy ribonucleic acid. What is
independent groups of researchers (Weimann et al.,
prescribed in the model is only that its raw materials
1968; Sulston et al., 1968; Schneider-Bernlohr et al.,
should be formed in the metabolic subsystem,
1968). Later, the possibility was pursued mainly by
polymer formation should occur on the surface of the
groups organised by Oró, Orgel and Lohrman.
template by copying its structure and in the process
However, other scientists also investigated the reality
a by-product should be produced in a stoichiometric
of non-enzymatic template polymerisation of ribonu-
quantity; the by-product is then utilised in a cleic acids by applying different condensing agents,
stoichiometric amount in the membrane formation. different conditions and different metal ions to the
In its simplest form, this can be the condensation polymerisation process (Ybanez et al., 1971a, b; Oró
product of the polycondensation process. In the & Stephan-Sherwood, 1974; Sawai, 1981; Sleeper &
minimum chemoton model shown here, this stoichio- Orgel, 1979; Sleeper et al., 1979; Lohrmann et al.,
metric combination is supposed. 1981; Orgel, 1983; etc.). Recently, the results of
The task of the information subsystem is to Kiedrowski and co-workers deserve most attention in
programme-control the operation of the whole this subject. In addition to well-reasoned stoichio-
supersystem. This programme is, at present, imagined metric aspects, the authors also study the chemical
and discussed as being coded in sign sequences. kinetic behaviour of these reaction systems. In their
However, in fact, this method of information storage latest work, they presented a template for the
is a later result of the development of information polymerisation processes of deoxyhexa-nucleotides
operations. Therefore, efforts to study the spon- (von Kiedrowski, 1986, 1993; von Kiedrowski et al.,
taneous abiogenic formation of information-carrying 1989, 1991; Sievers et al., 1994).
sequences without taking into account the formation However, these works have not yet determined the
and development of information utilising systems do formation of information subsystems in primordial
not lead—in actual fact, they cannot lead—to success. conditions, although the possibility of non-enzymatic
It can be shown that the programme-control of template polymerisation processes has been proven
self-reproducing chemical supersystems of the chemo- unambiguously.
ton type is also possible to determine without the
storage of information by sign sequences. This can be
done by means of stoichiometric control through the
fact that information on the system is being carried
by the signs built into the template. This becomes The Membrane Subsystem
more complicated if templates are built of two or The study of prebiotic membrane formation began
more different kinds of signs; in this case, besides the with some accidental discoveries. In the early 1960s
different amounts of the various signs and the total Sidney Fox prepared an aqueous solution of materials
amount of signs, the ratios of signs can also carry obtained by the heating of amino acids, and not only
information. determined the presence of water-soluble proteinoides
In the case of co-polymers built of more than one in the solution, but also water-insoluble, microscopic
sign, sign sequences can naturally be formed spheres of 1 mm in diameter, which he called
accidentally. These sign sequences are inherited by the proteinoide microspheres. The membrane surround-
descendant systems through the self-reproduction of ing these microspheres proved to be of a two-dimen-
the supersystem, and can have more or less errors in sional liquid nature (Fox, 1964, 1965, 1973, 1975).
590 . ́

spheres was detected by Krishna Bahadur from India, means of cycle stoichiometry, the whole metabolic
who irradiated solutions of ‘‘primordial soup’’ map of the chemical supersystem can be determined,
containing salts of molibdenum. He called the decomposed to elementary steps, and its stoichio-
microscopic spheres found in his reaction mixture metric relations can be calculated. Thus, by
Jeewanu (Bahadur, 1964, 1966a, 1967). Such micro- calculation alone, without time-consuming and costly
spheres have been obtained by irradiation with experiments, it can be decided whether the operation
UV-light performed by Fraser & Folsome. Their of any hypothetical variant is stoichiometrically
starting materials consisted of N2, CH4, CO2 and possible or not.
water. The authors also established that the Our working group constructed the whole meta-
formation of such microstructures is autocatalytic bolic map of a hypothetic, but concrete prebiotic
(Fraser & Folsome, 1975; Folsome, 1976, 1977; chemoton model [M. Hidvégi & T. Gánti, published
Folsome & Brittain, 1981). in Gánti (1989a)] and calculated its stoichiometry [E.
Kenyon and Nissenbaum prepared two kinds of Szathmáry & T. Gánti, published in Gánti (1989a)].
microspheres: from a solution of amino acids and This metabolic map contains the reactions of about
sugars, melanoidin-type microspheres were obtained, 100 intermediates; they are already partly known, and
whereas by simply letting a formaldehyde solution partly assumed to be prebiotic chemical reactions. In
of ammonium cyanide stand, aldocyanine micro- one cycle within the metabolic map, amounts of all
spheres were found in the solution (Kenyon & the components constituting the chemical supersys-
Nissenbaum, 1976; Polloch & Heiderer, 1979). tem (either product, or intermediate) become
Japanese scientists observed the development of stoichiometrically doubled, with the consumption of
microspheres in amino acid solutions which also given amounts of nutrients and the secretion of the
contained formaldehyde and had the composition of waste material. Nutrients are: (NC)2, NH2CN, HC4N,
modified sea-water, which they called marigranules or H2O, H2CO, HCN, NH4, Pi, HCONH2, H*; waste
marisomes. materials formed are: NCCONH2, CO(NH2)2, CO2;
These experiments can be justly called alchemist their amount is accurately determined by the overall
trials, in the sense that the given formations come into cyclic stoichiometric equation of the supersystem. H*
existence under appropriate chemical and physical means that the hydrogen originates from some
conditions, but without knowledge of the chemical undefined donor, among the nutrients.
details in the processes. In spite of this, these The basis of the metabolic subsystem of this
experiments clearly show that under the assumed concrete prebiotic chemoton is a formose reaction
primordial conditions, the general tendency has been network, which is autocatalytic ensuring thereby its
the formation of membrane-surrounded micro- own reproduction. Its information subsystem is a
spheres, i.e., compartmentalisation, which has oc- template process in which RNAs are formed from
curred under very different conditions and with very ribonucleotide-imidazolides with the liberation of
different compositions. imidazole on the template surface. Two subsystems
Recently, very good progress has been achieved, are connected to each other by two hypothetic
mainly resulting from the works of Luisi and his pathways: both start from the ribose evolved in the
research group. Their experiments are no longer formose network, but in one of them purin
alchemistic. They work with well-defined chemical nucleotides, in the other pyrimidine nucleotides or
substances, the reactions taking place can be followed their imidazolides are synthesised. Their quantitative
chemically, the autocatalytic nature of the formation relations are determined by the composition of
of their membranes can be measured experimentally. templates (hereditarily), thus here, before the
In their latest works—based on the results of appearance of information-carrying specific se-
Kiedrowski—they even determined template poly- quences, the programme-controlling role of templates
merisational replication within the microspheres is determined stoichiometrically.
(Bachmann et al., 1992; Böhler et al., 1994). Hidvégi suggested that a compound consisting of
glycerine diphytanol ether and imidazole formed
the basis of the membrane subsystem. Thus, the
The Programme-controlled, Self-reproducing, following pathway essentially connects membrane
Prebiotic Chemical Supersystem formation with the other two subsystems: glyceralde-
Until recently, no experiments had been performed hyde evolving in the formose reaction in phospho-
for the preparation of such systems although some rylised with acetyl phosphate, then it forms
laboratories had taken up the subject among their an ether-bond with two geranyl-geranyl pyrophos-
projects. On the basis of the chemoton model, by phate molecules. Subsequently, the side-chains are
   591

hydrogenised to phytanol, and the diphytanol ether subsystems. Thus, an extra pathway is needed for the
thus formed reacts with the imidazole liberated in synthesis of purin bases, for that of geranyl-geranyl
template polymerisation. pyrophosphate and for the production of acetyl
Several other connected pathways should also phosphate. This latter has two different roles: an
operate within the supersystem besides these three acetylating function and the role of a phosphate

RNA Membrane

RNA-polycon Membrane
Imidazolide
densation formation

Nucleotide
imidazolides

T-synthesis T
HCHO
Imidazolide
pathway

NH 3
P

Acetyl- P
Nucleotide cycle
cycle (regeneration)

NH3

Nucleotide
synthesis

HCN Glyceraldehyde
– P

Ribose

HCHO
P

Acetyl- P
Formose Glyceraldehyde synthesis
cycle
(de novo)

HCHO

F. 2. Scheme of the metabolic map for a concrete prebiotic chemoton. ‘‘T’’ is the sign for the membrane-forming molecule, in this
particular case the compound of glycerin diphytanol ether with imidazole.
592 . ́

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