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Origin of the Species
The Mystery of Life's Origins: Chapter 9
Specifying How Work is to be Done
In Chapter 7 we saw that the work necessary to polymerize DNA and protein
molecules from simple biomonomers could potentially be accomplished by
energy flow through the system. Still, we know that such energy flow is a
necessary but not sufficient condition for polymerization of the macromolecules
of life. Arranging a pile of bricks into the configuration of a house requires
work. One would hardly expect to accomplish this work with dynamite, however.
Not only must energy flow through the system, it must be coupled in some
specific way to the work to be done. This being so, we devoted Chapter 8 to
identifying various components of work in typical polymerization reactions. In
reviewing those individual work components, one thing became clear. The coupling
of energy flow to the specific work requirements in the formation of DNA and
protein is particularly important since the required configurational entropy
work of coding is substantial.
Theoretical Models for the Origin of DNA and Protein
A mere appeal to open system thermodynamics does little good. What must be done
is to advance a workable theoretical model of how the available energy
can be coupled to do the required work. In this chapter various theoretical
models for the origin of DNA and protein will be evaluated. Specifically, we
will discuss how each proposes to couple the available energy to the required
work, particularly the configurational entropy work of coding.
Before the specified complexity of living systems began to be appreciated, it
was thought that, given enough time, "chance" would explain the origin of living
systems. In fact, most textbooks state that chance is the basic explanation for
the origin of life. For example, Lehninger in his classic textbook
We now come to the critical moment in evolution in which the first semblance
of "life" appeared, through the chance association of a number of
abiotically formed macromolecular components, to yield a unique system of
greatly enhanced survival value.1
More recently the viability of "chance" as a mechanism for the origin of life
has been severely challenged.2
We are now ready to analyze the "chance" origin of life using the approach
developed in the last chapter. This view usually assumes that energy flow
through the system is capable of doing the chemical and the thermal entropy
work, while the configurational entropy work of both selecting and coding is the
fortuitous product of chance.
To illustrate, assume that we are trying to synthesize a protein containing 101
amino acids. In eq. 8-14 we estimated that the total free energy increase (G)
or work required to make a random polypeptide from previously selected amino
acids was 300 kcal/mole. An additional 159 kcal/mole is needed to code the
polypeptide into a protein. Since the "chance" model assumes no coupling between
energy flow and sequencing, the fraction of the polypeptide that has the correct
sequence may be calculated (eq. 8-16) using equilibrium thermodynamics, i.e.,
[protein concentration] / [polypeptide concentration] = exp ( -
= exp (-159,000) / 1.9872 x 298)
or approximately 1 x 10-117
This ratio gives the fraction of polypeptides that have the right sequence to be
[NOTE: This is essentially the inverse of the estimate for the number of
ways one can arrange 101 amino acids in a sequence (i.e., I /
in eq. 8-7)].
Eigen3 has estimated the number of polypeptides of molecular weight
10 4 (the same weight used in our earlier calculations) that would be
found in a layer 1 meter thick covering the surface of the entire earth. He
found it to be 1041. If these polypeptides reformed with new
sequences at the maximum rate at which chemical reactions may occur, namely 1014/s,
for 5 x 109 years [1.6 x 1017 s], the total number of
polypeptides that would be formed during the assumed history of the earth would
1041 x 1014/s x 1.6 x 1017s = 1072
Combining the results of eq. 9-1 and 9-2, we find the probability of producing
one protein of 101 amino acids in five billion years is only 1/ 1045.
Using somewhat different illustrations, Steinman4 and Cairns-Smith5
also come to the conclusion that chance is insufficient.
It is apparent that "chance" should be abandoned as an acceptable model for
coding of the macromolecules essential in living systems. In fact, it has been,
except in introductory texts and popularizations.
Neo-Darwinian Natural Selection
The widespread recognition of the severe improbability that self-replicating
organisms could have formed from purely random interactions has led to a great
deal of speculation---speculation that some organizing principle must have been
involved. In the company of many others, Crick6 has considered that
the neo-Darwinian mechanism of natural selection might provide the answer. An
entity capable of self-replication is necessary, however, before natural
selection can operate. Only then could changes result via mutations and
environmental pressures which might in turn bring about the dominance of
entities with the greatest probabilities of survival and reproduction.
The weakest point in this explanation of life's origin is the great complexity
of the initial entity which must form, apparently by random fluctuations, before
natural selection can take over. In essence this theory postulates the chance
formation of the "metabolic motor" which will subsequently be capable of
channeling energy flow through the system. Thus harnessed by coupling through
the metabolic motor, the energy flow is imagined to supply not only chemical and
thermal entropy work, but also the configurational entropy work of selecting the
appropriate chemicals and then coding the resultant polymer into an aperiodic,
specified, biofunctioning polymer. As a minimum, this system must carry in its
structure the information for its own synthesis, and control the machinery which
will fabricate any desired copy. It is widely agreed that such a system requires
both protein and nucleic acid.7 This view is not unanimous, however.
A few have suggested that a short peptide would be sufficient.8
One way out of the problem would be to extend the concept of natural selection
to the pre-living world of molecules. A number of authors have entertained this
possibility, although no reasonable explanation has made the suggestion
plausible. Natural selection is a recognized principle of differential
reproduction which presupposes the existence of at least two distinct types of
self-replicating molecules. Dobzhansky appealed to those doing origin-of-life
research not to tamper with the definition of natural selection when he said:
I would like to plead with you, simply, please realize you cannot use the
words "natural selection" loosely. Prebiological natural selection is a
contradiction in terms.9
Bertalanffy made the point even more cogently:
Selection, i.e., favored survival of "better" precursors of life, already
presupposes self-maintaining, complex, open systems which may compete;
therefore selection cannot account for the origin of such systems.10
Inherent Self-Ordering Tendencies in Matter
How could energy flow through the system be sufficiently coupled to do the
chemical and thermal entropy work to form a nontrivial yield of polypeptides (as
previously assumed in the "chance" model)? One answer has been the suggestion
that configurational entropy work, especially the coding work, could occur as a
consequence of the self-ordering tendencies in matter. The experimental work of
Steinman and Cole11 in the late Sixties is still widely cited in
support of this model.12 The polymerization of protein is
hypothesized to be a nonrandom process, the coding of the protein
resulting from differences in the chemical bonding forces. For example, if amino
acids A and B react chemically with one another more readily than with amino
acids C, D, and E, we should expect to see a greater frequency of AB peptide
bonds in protein than AC, AD, AE, or BC, BD, BE bonds.
Together with our colleague Randall Kok, we have recently analyzed the ten
proteins originally analyzed by Steinman and Cole,13 as well as
fifteen additional proteins whose structures (except for hemoglobin) have been
determined since their work was first published in 1967. Our expectation in this
study was that one would only get agreement between the dipeptide bond
frequencies from Steinman and Cole's work and those observed in actual proteins
if one considered a large number of proteins averaged together. The distinctive
structures of individual proteins would cause them to vary greatly from Steinman
and Cole's data, so only when these distinctives are averaged out could one
expect to approach Steinman and Cole's dipeptide bond frequency results. The
reduced data presented in table 9-1 shows that Steinman and Cole's dipeptide
bond frequencies do not correlate well with the observed peptide bond
frequencies for one, ten, or twenty-five proteins. It is a simple matter to make
such calculations on an electronic digital computer. We surmise that additional
assumptions not stated in their paper were used to achieve the better
Furthermore, the peptide bond frequencies for the twenty-five proteins approach
a distribution predicted by random statistics rather than the dipeptide bond
frequency measured by Steinman and Cole. This observation means that bonding
preferences between various amino acids play no significant role in coding
protein. Finally, if chemical bonding forces were influential in amino acid
sequencing, one would expect to get a single sequence (as in ice crystals) or no
more than a few sequences, instead of the large variety we observe in living
systems. Yockey, with a different analysis, comes to essentially the same
A similar conclusion may be drawn for DNA synthesis. No one to date has
published data indicating that bonding preferences could have had any role in
coding the DNA molecules. Chemical bonding forces apparently have minimal effect
on the sequence of nucleotides in a polynucleotide.
Comparison of Steinman and Cole's experimentally determined dipeptide bond
frequencies, and frequencies calculated by Steinman and Cole, and by Kok and
Bradley from known protein sequences.
Values (relative to Gly-Gly)
S / C+
K / B #
1.0 (1.0) [1.0]
1.0 (1.0) [1.0]
1.1 (1.1) [2.0]
2.0 (1.2) [1.0]
1.0 (1.1) [2.2]
1.5 (1.2) [0.0]
1.3 (1.5) [4.4]
2.8 (1.5) [0.0]
0.2 (0.3) [0.4]
1.5 (1.2) [1.0]
0.3 (0.3) [0.6]
0.8 (0.6) [0.0]
0.3 (0.3) [0.2]
1.3 (0.7) [1.0]
0.3 (0.3) [0.8]
1.3 (1.0) [1.0]
0.1 (0.2) [0.6]
1.0 (0.8) [0.0]
0.1 (0.2) [0.2]
0.0 (0.4) [0.0]
0.1 (0.2) [0.4]
0.5 (0.5) [0.0]
0.1 (0.1) [0.6]
1.0 (0.5) [1.0]
(Adapted after G. Steinman and M.V. Cole, 1967. Proc. Nat. Acad. Sci. U.S.
* The dipeptides are listed in terms of increasing volume of the side chains of
the constituent residues. Gly = glycine, Ala = alanine, Val = valine, Leu =
leucine, Ile = isoleucine and Phe = phenylalanine. Example: Gly-Ala =
+ Steinman and Cole's (S/C) experimentally determined dipeptide bond frequencies
were normalized and compared to the calculated frequencies obtained by counting
actual peptide bond frequencies in ten proteins, assuming all seryl and threonyl
residues are counted as glycine and all aspartyl and glutamyl residues are
counted as alanine. The ten proteins used were: egg lysozyme, ribonuclease,
sheep insulin, whale myoglobin, yeast cytochrome c, tobacco mosaic virus,
beta-corticotropin, glucagon, melanocyte-stimulating hormone, and
chymotrypsinogen. Because of ambiguity regarding sequences used by S/C, all
sequences are those shown in Atlas of Protein Sequence and Structure,
1972. Vol. V (ed. by M.O. Dayhoff). National Biomedical Research Foundation,
Georgetown University Medical Center, Washington, D.C.
& The experimentally determined dipeptide frequencies were obtained with aqueous
solutions containing 0.01 M each amino acid, 0.125 N HCl, 0.1 M sodium
#Kok and Bradley's (K/Bcalculated dipeptide frequencies were obtained by
counting S?Cassumptions. The numbers in brackets are for one protein,
enterotoxin B, with actual peptide bond frequencies for the same ten proteins
with (wa) and without (woa) S/C assumptions. The numbers in parentheses are for
twenty-five proteins with (wa) and without (woa) S/C assumptions. The
twenty-five proteins are the ten used S/C and alpha S1 Casein (bovine); azurin
(bordetella bronchisetica); carboxypeptidase A (bovine); cytochrome b5 (bovine);
enterotoxin B; elastase (pig); glyceraldehyde 3-phosphate dehydrogenase
(lobster); human growth hormone; human hemoglobin beta chain; histone 11B2
(bovine); immunoglobulin gamma-chain 1, V-I (human EU); penicillinase (bacillus
licheniformis 749/c); sheep prolactin; subtilisin (bacillus amyloliquefaciens);
and tryptophan synthetase alpha chain (E-coh K-i 2). Sequences are
those shown in Atlas of Protein Sequence and Structure, 1972. Vol.
V (ed. by M.O. Dayhoff). Note disagreement S/C K/B calculated results. Also S/C
calculated results are at variance with S/C experimental values for one, ten or
twenty-five proteins, with (wa) or without (woa) S/C assumptions.
Mineral catalysis is often suggested as being significant in prebiotic
evolution. In the experimental investigations reported in the early 1970's15
mineral catalysis in polymerization reactions was found to operate by adsorption
of biomonomers on the surface or between layers of clay. Monomers were
effectively concentrated and protected from rehydration so that condensation
polymerization could occur. There does not appear to be any additional effect.
In considering this catalytic effect of clay, Hulett has advised, "It must be
remembered that the surface cannot change the free energy relationships between
reactants and products, but only the speed with which equilibrium is reached."16
Is mineral catalysis capable of doing the chemical work and/or thermal entropy
work? The answer is a qualified no. While it should assist in doing the thermal
entropy work, it is incapable of doing the chemical work since clays do not
supply energy. This is why successful mineral catalysis experiments invariably
use energy-rich precursors such as aminoacyl adenylates rather than amino acids.17
Is there a real prospect that mineral catalysis may somehow accomplish the
configurational entropy work, particularly the coding of polypeptides or
polynucleotides? Here the answer is clearly no. In all experimental work to
date, only random polymers have been condensed from solutions of selected
ingredients. Furthermore, there is no theoretical basis for the notion that
mineral catalysis could impart any significant degree of information content to
polypeptides or polynucleotides. As has been noted by Wilder-Smith,18
there is really no reason to expect the low-grade order resident on minerals to
impart any high degree of coding to polymers that condense while adsorbed on the
mineral's surface. To put it another way, one cannot get a complex,
aperiodic-sequenced polymer using a very periodic (or crystalline) template.
In summary, mineral catalysis must be rejected as a mechanism for doing either
the chemical or configurational entropy work required to polymerize the
macromolecules of life. It can only assist in polymerizing short, random chains
of polymers from selected high-energy biomonomers by assisting in doing the
thermal entropy work.
Nonlinear, Nonequilibrium Processes
1. Ilya Prigogine
Prigogine has developed a more general formulation of the laws of thermodynamics
which includes nonlinear, irreversible processes such as autocatalytic activity.
In his book Self Organization in Nonequilibrium Systems (1977)19
co-authored with Nicolis, he summarized this work and its application to the
organization and maintenance of highly complex structures in living things. The
basic thesis in the book is that there are some systems which obey non-linear
laws---laws that produce two distinct kinds of behavior. In the neighborhood of
thermodynamic equilibrium, destruction of order prevails (entropy achieves a
maximum value consistent with the system constraints). If these same systems are
driven sufficiently far from equilibrium, however, ordering may appear
Heat flow by convection is an example of this type of behavior. Heat conduction
in gases normally occurs by the random collision of gas molecules. Under certain
conditions, however, heat conduction may occur by a heat-convection
current---the coordinated movement of many gas molecules. In a similar way,
water flow out of a bathtub may occur by random movement of the water molecules
under the influence of gravity. Under certain conditions, however, this random
movement of water down the drain is replaced by the familiar soapy swirl---the
highly coordinated flow of the vortex. In each case random movements of
molecules in a fluid are spontaneously replaced by a highly ordered behavior.
Prigogine et al.,20 Eigen,21 and others have
suggested that a similar sort of self-organization may be intrinsic in organic
chemistry and can potentially account for the highly complex macromolecules
essential for living systems.
But such analogies have scant relevance to the origin-of-life question. A major
reason is that they fail to distinguish between order and complexity. The highly
ordered movement of energy through a system as in convection or vortices suffers
from the same shortcoming as the analogies to the static, periodic order of
crystals. Regularity or order cannot serve to store the large amount of
information required by living systems. A highly irregular, but specified,
structure is required rather than an ordered structure. This is a serious flaw
in the analogy offered. There is no apparent connection between the kind of
spontaneous ordering that occurs from energy flow through such systems and the
work required to build aperiodic information-intensive macromolecules like DNA
and protein. Prigogine, et al.22 suggest that the energy
flow through the system decreases the system entropy, leading potentially to the
highly organized structure of DNA and protein. Yet they offer no suggestion as
to how the decrease in thermal entropy from energy flow through the system could
be coupled to do the configurational entropy work required.
A second reason for skepticism about the relevance of the models developed by
Prigogine, et al.23 and others is that ordering produced
within the system arises through constraints imposed in an implicit way at the
system boundary. Thus, the system order, and more importantly the system
complexity, cannot exceed that of the environment.
Walton24 illustrates this concept in the following way. A container
of gas placed in contact with a heat source on one side and a heat sink on the
opposite side is an open system. The flow of energy through the system from the
heat source to the heat sink forms a concentration relative to the gas in the
cooler region. The order in this system is established by the structure:
source-intermediate systems-sink. If this structure is removed, allowing the
heat source to come into contact with the heat sink, the system decays back to
equilibrium. We should note that the information induced in an open system
doesn't exceed the amount of information built into the structural environment,
which is its source.
Condensation of nucleotides to give polynucleotides or nucleic acids can be
brought about with the appropriate apparatus (i.e., structure) and supplies of
energy and matter. Just as in Walton's illustration, however, Mora25has
shown that the amount of order (not to mention specified complexity) in the
final product is no greater than the amount of information introduced in the
physical structure of the experiment or chemical structure of the reactants.
Non-equilibrium thermodynamics does not account for this structure, but assumes
it and then shows the kind of organization which it produces. The origin and
maintenance of the structure are not explained, and as Harrison26
correctly notes this question leads back to the origin of structure in the
universe. Science offers us no satisfactory answer to this problem at present.
Nicolis and Prigogine27 offer their trimolecular model as an example
of a chemical system with the required nonlinearity to produce self ordering.
They are able to demonstrate mathematically that within a system that was
initially homogeneous, one may subsequently have a periodic, spatial variation
of concentration. To achieve this low degree of ordering, however, they must
require boundary conditions that could only be met at cell walls (i.e., at
membranes), relative reaction rates that are atypical of those observed in
condensation reactions, a rapid removal of reaction flow products, and a
trimolecular reaction (the highly unlikely simultaneous collision of three
atoms). Furthermore the trimolecular model requires chemical reactions that are
essentially irreversible. But condensation reactions for polypeptides or
polynucleotides are highly reversible unless all water is removed from the
They speculate that the low degree of spatial ordering achieved in the simple
trimolecular model could potentially be orders of magnitude greater for the more
complex reactions one might observe leading up to a fully replicating cell. The
list of boundary constraints, relative reaction rates, etc. would, however, also
be orders of magnitude larger. As a matter of fact, one is left with so
constraining the system at the boundaries that ordering is inevitable from the
structuring of the environment by the chemist. The fortuitous satisfaction of
all of these boundary constraints simultaneously would be a its miracle in its
It is possible at present to synthesize a few proteins such as insulin in the
laboratory. The chemist supplies not only energy to do the chemical and thermal
entropy work, however, but also the necessary chemical manipulations to
accomplish the configurational entropy work. Without this, the selection of the
proper composition and the coding for the right sequence of amino acids would
not occur. The success of the experiment is fundamentally dependent on the
Finally, Nicolis and Prigogine have postulated that a system of chemical
reactions which explicitly shows autocatalytic activity may ultimately be able
to circumvent the problems now associated with synthesis of prebiotic DNA and
protein. It remains to be demonstrated experimentally, however, that
these models have any real correspondence to prebiotic condensation reactions.
At best, these models predict higher yields without any mechanism to control
sequencing. Accordingly, no experimental evidence has been reported to show how
such models could have produced any significant degree of coding. No, the models
of Prigogine et al., based on non-equilibrium thermodynamics, do not at
present offer an explanation as to how the configurational entropy work is
accomplished under prebiotic conditions. The problem of how to couple energy
flow through the system to do the required configurational entropy work
2. Manfred Eigen
In his comprehensive application of nonequilibrium thermodynamics to the
evolution of biological systems, Eigen28 has shown that selection
could produce no evolutionary development in an open system unless the system
were maintained far from equilibrium. The reaction must be autocatalytic but
capable of self-replication. He develops an argument to show that in order to
produce a truly self-replicating system the complementary base-pairing
instruction potential of nucleic acids must be combined with the catalytic
coupling function of proteins. Kaplan29 has suggested a minimum of
20-40 functional proteins of 70-100 amino acids each, and a similar number of
nucleic acids would be required by such a system. Yet as has previously been
noted, the chance origin of even one protein of 100 amino acids is essentially
The shortcoming of this model is the same as for those previously discussed;
namely, no way is presented to couple the energy flow through the system to
achieve the configurational entropy work required to create a system capable of
Periodically we see reversions (perhaps inadvertent ones) to chance in the
theoretical models advanced to solve the problem. Eigen's model illustrates this
well. The model he sets forth must necessarily arise from chance events and is
nearly as incredible as the chance origin of life itself. The fact that
generally chance has to be invoked many times in the abiotic sequence has been
called by Brooks and Shaw "a major weakness in the whole chemical evolutionary
Experimental Results in Synthesis of Protein and DNA
Thus far we have reviewed the various theoretical models proposed to explain how
energy flow through a system might accomplish the work of synthesizing protein
and DNA macromolecules, but found them wanting. Nevertheless, it is conceivable
that experimental Support for a spontaneous origin of life can be found in
advance of the theoretical explanation for how this occurs. What then can be
said of the experimental efforts to synthesize protein and DNA macromolecules?
Experimental efforts to this end have been enthusiastically pursued for the past
thirty years. In this section, we will review efforts toward the prebiotic
syntheses of both protein and DNA, considering the three forms of energy flow
most commonly thought to have been available on the early earth. These are
thermal energy (volcanoes), radiant energy (sun), and chemical energy in the
form of either condensing agents or energy-rich precursors. (Electrical energy
is excluded at this stage of evolution as being too "violent," destroying rather
than joining the biomonomers.)
Sidney Fox31 has pioneered the thermal synthesis of polypeptides,
naming the products of his synthesis proteinoids. Beginning with either
an aqueous solution of amino acids or dry ones, he heats his material at 2000oC
for 6-7 hours.
[NOTE: Fox has modified this picture in recent years by developing "low
temperature" syntheses, i.e., 90-120oC. See S. Fox, 1976. J
Mol Evol 8, 301; and D. Rohlfing, 1976.
Science 193, 68].
All initial solvent water, plus water produced during Polymerization, is
effectively eliminated through vaporization. This elimination of the water makes
possible a small but significant yield of polypeptides, some with as many as 200
amino acid units. Heat is introduced into the system by conduction and
convection and leaves in the form of steam. The reason for the success of the
polypeptide formation is readily seen by examining again equations 8-15 and
8-16. Note that increasing the temperature would increase the product yield
through increasing the value of exp (-
/ RT. But more importantly, eliminating the water makes the reaction
irreversible, giving an enormous increase in yield over that observed under
equilibrium conditions by the application of the law of mass action.
Thermal syntheses of polypeptides fail, however, for at least four reasons.
First, studies using nuclear magnetic resonance (NMR) have shown that thermal
proteinoids "have scarce resemblance to natural peptidic material because beta,
gamma, and epsilon peptide bonds largely predominate over alpha-peptide bonds."32
[NOTE: This quotation refers to peptide links involving the beta-carboxyl
group of aspartic acid, the gamma-carboxyl group of glutamic acid, and the
epsilon-amino group of lysine which are never found in natural proteins.
Natural proteins use alpha-peptide bonds exclusively].
Second, thermal proteinoids are composed of approximately equal numbers of L-
and D-amino acids in contrast to viable proteins with all L-amino acids. Third,
there is no evidence that proteinoids differ significantly from a random
sequence of amino acids, with little or no catalytic activity. [It is noted,
however, that Fox has long disputed this.] Miller and Orgel have made the
following observation with regard to Fox's claim that proteinoids resemble
The degree of nonrandomness in thermal polypeptides so far demonstrated is
minute compared to nonrandomness of proteins. It is deceptive, then, to
suggest that thermal polypeptides are similar to proteins in their
Fourth, the geological conditions indicated are too unreasonable to be taken
seriously. As Folsome has commented, "The central question [concerning Fox's
proteinoids] is where did all those pure, dry, concentrated, and optically
active amino acids come from in the real, abiological world?"34
There is no question that thermal energy flow through the system including the
removal of water is accomplishing the thermal entropy and chemical work required
to form a polypeptide (300 kcal/mole in our earlier example). The fact that
polypeptides are formed is evidence of the work done. It is equally clear that
the additional configurational entropy work required to convert an aperiodic
unspecified polypeptide into a specified, aperiodic polypeptide which is a
functional protein has not been done (159 kcal/mole in our earlier example).
It should be remembered that this 159 kcal/mole of configurational entropy work
was calculated assuming the sequencing of the amino acids was the only
additional work to be done. Yet the experimental results of Temussi et al.,35
indicate that obtaining all Lamino acids from a racemic mixture and getting
alpha-linking between the amino acids are quite difficult. This requirement
further increases the configurational entropy work needed over that estimated to
do the coding work (159 kcal/mole). We may estimate the magnitude of this
increase in the configurational entropy work term by returning to our original
calculations (eq. 8-7 and 8-8).
In our original calculation for a hypothetical protein of 100 amino acid units,
we assumed the amino acids were equally divided among the twenty types. We
calculated the number of possible amino acid sequences as follows:
= 100! / 5! 5! 5!....5! = 100! / (5!)20 = 1.28 x 10115
If we note that at each site the probability of having an L-amino acid is 50%,
and make the generous assumption that there is a 50% probability that a given
link will be of the alpha-type observed in true proteins, then the number of
ways the system can be arranged in a random chemical reaction is given by
= 1.28 x 10115 x 2100 x 299 = 10175
where 2100 refers to the number of additional arrangements possible,
given that each site could contain an L- or D-amino acid, and 299
assumes the 99 links between the 100 amino acids in general are equally divided
between the natural alpha-links and the unnatural beta-, gamma-, or
[NOTE Some studies indicate less than 50% alpha-links in peptides formed by
reacting random mixtures of amino acids. (P.A. Temussi, L. Paolillo, F.E.
Benedetti, and S. Andini, 1976. J. Mol. Evol. 7,
The requirements for a biologically functional protein molecule are: (1) all
L-amino acids, (2) all alpha-links, and (3) a specified sequence. This being so,
the calculation of the configurational entropy of the protein molecule using
equation 8-8 is unchanged except that the number of ways the system can be
is increased from 1.28 x 10115 to 1.0 x 10175 as shown in
equations 9-3 and 9-4. We may use the relationships of equations 8-7 and 8-8 but
with the number of permutations modified as shown here to find a total
configurational entropy work. When we do, we get a total configurational entropy
work of 195 kcal/mole, of which 159 kcal/mole is for sequencing and 36 kcal/mole
to attain all L-amino acids and all alpha-links. Finally, it should be
recognized that Fox and others who use his approach avoid a much larger
configurational entropy work term by beginning with only amino acids, i.e.,
excluding other organic chemicals and thereby eliminating the "selecting work"
which is not accounted for in the 195 kcal/mole calculated above.
In summary, undirected thermal energy is only able to do the chemical and
thermal entropy work in polypeptide synthesis, but not the coding (or
sequencing) portion of the configurational entropy work. Protenoids are just
globs of random polymers. That a polymer composed exclusively of amino acids
(but without exclusively peptide bonds) was formed is a result of the fact that
only amino acids were used in the experiment. Thus, the portion of the
configurational entropy work that was done---the selecting work---was
accomplished not by natural forces but by illegitimate investigator
interference. It is difficult to imagine how one could ever couple random
thermal energy flow through the system to do the required configurational
entropy work of selecting and sequencing. Finally, this approach is of very
questionable geological significance, given the many fortuitous events that are
required, as others have noted.
Direct photochemical (UV) polymerization reactions to form polypeptides and
polynucleotides have occasionally been discussed in the literature. The idea is
to drive forward the otherwise thermodynamically unfavorable polymerization
reaction by allowing solar energy to flow through the aqueous system to do the
necessary work. It is worth noting that minor yields of small peptides can be
expected to form spontaneously, even though the reaction is unfavorable (see eq.
8-16), but that greater yields of larger peptides can be expected only if energy
is somehow coupled to the reaction. Fox and Dose have examined the peptide
results of Bahadur and Ranganayaki36 and concluded that UV
irradiation did not couple with the reaction. They comment, "The authors do not
show that they have done more than accelerate an approach to an unfavorable
equilibrium. They may merely have reaffirmed the second law of thermodynamics."37
Other attempts to form polymers directly under the influence of UV light have
not been encouraging because of this lack of coupling. Neither the chemical nor
the thermal entropy work, and definitely not any configurational entropy work,
has been accomplished using solar energy.
Chemical Energy (Energy-Rich Condensing Agents)
Through the use of condensing agents, the energetically unfavorable dipeptide
= + 3000 cal/mole) is made energetically favorable (G3
< 0) by coupling it with a second reaction which is sufficiently favorable
< 0), to offset the energy requirement of the dipeptide reaction:
A - OH + H - B
A - B + H20
condensing agent reaction
C + H20
A - OH + H - B + C
A - B + D
As in thermal proteinoid formation, the free water is removed. However, in this
case, it is removed by chemical reaction with a suitable poly- condensing
agent-one which has a sufficient decrease in Gibbs free energy to drive the
reaction forward (i.e.,
0 and |
|G1 | so that
Unfortunately, it has proved difficult to find condensing agents work. for these
macromolecule syntheses that could have originated on the primitive earth and
functioned properly under mild conditions in an aqueous environment.38
Meanwhile, other condensing agents which are not prebiotically significant
(e.g., polymetaphosphates) are used in experiments. The plausible cyanide
derivative candidates for condensing agents on the early earth hydrolyze readily
in aqueous solutions (see Chapter 4). In the process, they do not couple
preferentially with the H20 from the condensation-dehydration
reaction. Condensing agents observed in living systems today are produced only
by living systems, and thus are not prebiotically significant. Moreover, enzyme
activity in living systems first activates amino acids and then brings about
condensation of these activated species, thus avoiding the problem of
indiscriminate reaction with water.
Notice that if we could solve the very significant problems associated with the
prebiotic synthesis of polypeptides by using condensing agents, we would still
succeed only in polymerizing random polypeptides. Only the chemical and thermal
entropy work would be accomplished by an appropriate coupling of the condensing
agent to the condensation reaction. There is no reason to believe that
condensing agents could have any effect on the selecting or sequencing of the
amino acids. Thus, condensing agents are eliminated as a possible means of doing
the configurational entropy work of coding a protein or DNA.
Chemical Energy (Energy-Rich Precursors)
Because the formation of even random polypeptides from amino acids is so
energetically unfavorable (G
= 300 kcal/mole for 100 amino acids), some investigators have attempted to begin
with energy-rich precursors such as HCN and form polypeptides directly, a scheme
which is "downhill" energetically, i.e.,
< 0. There are advantages to such an approach; namely, there is no chemical work
to be done since the bonding energy actually decreases as the energy-rich
precursors react to form more complex molecules. This decrease in bonding energy
will drive the reaction forward, effectively doing the thermal entropy work as
well. The fly in the ointment, however, is that the configurational entropy work
is enormous in going from simple molecules (e.g., HCN) directly to complex
polymers in a single step (without forming intermediate biomonomers).
The stepwise scheme of experiments is to react gases such as methane, ammonia,
and carbon dioxide to form amino acids and other compounds and then to react
these to form polymers in a subsequent experiment. In these experiments the very
considerable selecting-work component of the configurational entropy work is
essentially done by the investigator who separates, purifies, and concentrates
the amino acids before attempting to polymerize them. Matthews39 and
co-workers, however, have undertaken experiments where this intermediate step is
missing and the investigator has no opportunity to contribute even obliquely to
the success of the experiment by assisting in doing the selecting part of the
configurational entropy work. In such experiments-undoubtedly more plausible as
true prebiotic simulations-the probability of success is, however, further
reduced from the already small probabilities previously mentioned. Using HCN as
an energy-rich precursor, and ammonia as a catalyst, Matthews and Moser40
have claimed direct synthesis of a large variety of chemicals under anhydrous
conditions. After treating the polymer with water, even peptides are said to be
among the products obtained. But as Ferris et al.,41 have
shown, the HCN polymer does not release amino acids upon treatment with
proteolytic (protein splitting) enzymes; nor does it give a positive biuret
reaction (color test for peptides). In short, it is very hard to reconcile these
results with a peptidic structure.
Ferris42 and Matthews43 have agreed that direct synthesis
of polypeptides has not yet been demonstrated. While some peptide bonds may form
directly, it would be quite surprising to find them in significant numbers.
Since HCN gives rise to other organic compounds, and various kinds of links are
possible, the formation of polypeptides with exclusively alpha-links is most
unlikely. Furthermore, no sequencing would be expected from this reaction, which
is driven forward and "guided" only by chemical energy.
While we do not believe Matthews or others will be successful in demonstrating a
single step synthesis of polypeptides from HCN, this approach does involve the
least investigator interference, and thus, represents a very plausible prebiotic
simulation experiment. The approach of Fox and others, which involves reacting
gases to form many organic compounds, separating out amino acids, purifying, and
finally polymerizing them, is more successful because it involves a greater
measure of investigator interference. The selecting portion of the
configurational entropy work is being supplied by the scientist. Matthew's lack
of demonstrable success in producing polypeptides is a predictable indication of
the enormity of the problem of prebiotic synthesis when it is not overcome by
illegitimate investigator interference.
A novel synthesis of polypeptides has been reported44 which employs
mineral catalysis. An aqueous solution of energy-rich aminoacyl adenylates
(rather than amino acids) is used in the presence of certain layered clays such
as those known as montmorillonites. Large amounts of the energy-rich reactants
are adsorbed both on the surface and between the layers of clay. The catalytic
effect of the clay may result primarily from the removal of reactants from the
solution by adsorption between the layers of clay. This technique has resulted
in polypeptides of up to 50 units or more. Although polymerization definitely
occurs in these reactions, the energy-rich aminoacyl adenylate (fig. 9-1) is of
very doubtful prebiotic significance per the discussion of competing reactions
in Chapter 4. Furthermore, the use of clay with free amino acids will not give a
successful synthesis of polypeptides. The energy-rich aminoacyl adenylates lower
their chemical or bonding energy as they polymerize, driving the reaction
forward, and effectively doing the thermal entropy work as well. The role of the
clay is to concentrate the reactants and possibly to catalyze the reactions.
Once again, we are left with no apparent means to couple the energy flow, in
this case in the form of prebiotically questionable energy-rich precursors, to
the configurational entropy work of selecting and sequencing required in the
formation of specified aperiodic polypeptides, or proteins.
Aminoacyl adenylate. Summary of Experimental Results on
Prebiotic Synthesis of protein
In summary, we have seen that it is possible to do the thermal entropy work and
chemical work necessary to form random polypeptides, e.g., Fox's proteinoids. In
no case, though, has anyone been successful in doing the additional
configurational entropy work of coding necessary to convert random polypeptides
into proteins. Virtually no mechanism with any promise for coupling the random
flow of energy through the system to do this very specific work has come to
light. The prebiotic plausibility of the successful synthesis of polypeptides
must be questioned because of the considerable configurational entropy work of
selecting done by the investigator prior to the polymer synthesis. Surely no
suggestion is forthcoming that the right composition of just the subset of amino
acids found in living things was "selected" by natural means, or that this
subset consists only of L-a-amino acids. This is precisely why a large measure
of the credit in forming proteinoids must go to Fox and others rather than
Summary of Experimental Results on Prebiotic Synthesis of DNA
The prebiotic synthesis of DNA has proved to be even more difficult than that of
protein. The problems that beset protein synthesis apply with greater force to
DNA synthesis. Energy flow through the system may cause the nucleotides to
chemically react and form a polymer chain, but it is very difficult to get them
to attach themselves together in a specified way. For example, 3' - 5' links on
the sugar are necessary for the DNA to form a helical structure (see fig. 9-2).
Yet 2'-5' links predominate in most prebiotic simulation experiments.45
The sequencing of the bases in DNA is also crucial, as is the amino acid
sequence in proteins. Both of these requirements are problems in doing the
configurational entropy work. It is one thing to get molecules to chemically
react; it is quite another to get them to link up in the right arrangement. To
date, researchers have only succeeded in making oligonucleotides, or relatively
short chains of nucleotides, with neither consistent 3'-5' links nor specific
A section from a DNA chain showing the sequence AGCT.
Miller and Orgel summarized their chapter on prebiotic condensation reactions by
This chapter has probably been confusing to the reader. We believe that is
because of the limited progress that has been made in the study of prebiotic
condensation. Many interesting scraps of information are available, but no
correct pathways have yet been discovered.46
The situation is much the same today.
Summary Discussion of Experimental Results
There is an impressive contrast between the considerable success in synthesizing
amino acids and the consistent failure to synthesize protein and DNA. We believe
the reason is the large difference in the magnitude of the configurational
entropy work required. Amino acids are quite simple compared to protein, and one
might reasonably expect to get some yield of amino acids, even where the
chemical reactions that occur do so in a rather random fashion. The same
approach will obviously be far less successful in reproducing complex protein
and DNA molecules where the configurational entropy work term is a nontrivial
portion of the whole. Coupling the energy flow through the system to do the
chemical and thermal entropy work is much easier than doing the configurational
entropy work. The uniform failure in literally thousands of experimental
attempts to synthesize protein or DNA under even questionable prebiotic
conditions is a monument to the difficulty in achieving a high degree of
information content, or specified complexity from the undirected flow
of energy through a system.
We must not forget that the total work to create a living system goes far beyond
the work to create DNA and protein discussed in this chapter. As we stated
before, a minimum of 20-40 proteins as well as DNA and RNA are required to make
even a simple replicating system. The lack of known energy-coupling means to do
the configurational entropy work required to make DNA and protein is many times
more crucial in making a living system. As a result, appeals to chance for this
most difficult problem still appear in the literature in spite of the fact that
calculations give staggeringly low probabilities, even on the scale of 5 billion
years. Either the work---especially the organizational work---was coupled to the
flow of energy in some way not yet understood, or else it truly was a miracle.
Summary of Thermodynamics Discussion
Throughout Chapters 7-9 we have analyzed the problems of complexity and the
origin of life from a thermodynamic point of view. Our reason for doing this is
the common notion in the scientific literature today on the origin of life that
an open system with energy and mass flow is a priori a sufficient
explanation for the complexity of life. We have examined the validity of such an
open and constrained system. We found it to be a reasonable explanation for
doing the chemical and thermal entropy work, but clearly inadequate to account
for the configurational entropy work of coding (not to mention the sorting and
selecting work). We have noted the need for some sort of coupling mechanism.
Without it, there is no way to convert the negative entropy associated with
energy flow into negative entropy associated with configurational entropy and
the corresponding information. Is it reasonable to believe such a "hidden"
coupling mechanism will be found in the future that can play this crucial role
of a template, metabolic motor, etc., directing the flow of energy in such a way
as to create new information?
1. Albert L. Lehninger, 1970. Biochemistry. New York: Worth
2. H.P. Yockey, 1977. J. Theoret. Biol. 67, 377; R.W. Kaplan, 1974.
Rad. Environ. Biophys. 10, 31.
3. M. Eigen, 1971. Die Naturwiss. 58, 465.
4. G. Steinman, 1967. Arch. Biochem. Biophys. 121,
533. 5. A.G. Cairns-Smith, 1971. The Life Puzzle. Edinburgh: Oliver
6. F. Crick, 1966. Of Molecules and Men. Seattle: University of
Washington Press, p. 6-7.
7. Eigen, Die Naturwiss., p. 465; S.L. Miller and L.E. Orgel, 1974.
The Origins of Life on the Earth. Englewood Cliffs, New Jersey:
8. J.B.S. Haldane, 1965. In The Origins of Prebiological Systems and of
Their Molecular Matrices, ed. S.W. Fox. New York: Academic Press, p.11.
9. T. Dobzhansky, 1965. In The Origins of Prebiological Systems and of
Their Molecular Matrices, p.310.
10. Ludwig von Bertalanffy, 1967. Robots, Men and Minds. New York:
George Braziller, p.82.
11. G. Steinman and M. Cole, 1967. Proc. Nat. Acad. Sci. U.S.
58, 735; Steinman, Arch. Biochem. Biophys. ,
12. A. Katchalsky, 1973. Die Naturwiss. 60,215; M. Calvin, 1975.
Amer. Sci. 63, 169; C.E. Folsome, 1979. The
Origin of Life. San Francisco: W.H. Freeman, p.104; K. Dose, 1983.
Naturwiss. 70, 378.
13. Steinman, Arch. Biochem. Biophys. 121, 533;
Steinman and Cole, Proc. Nat. Acad. Sci. U.S. 5,
14. H.P. Yockey, 1981. J. Theoret. Biol 91, 13.
15. Katchalsky, Die Naturwiss., p.215.
16. H.R. Hulett, 1969. J. Theoret. Biol 24, 56.
17. Katchalsky, Die Naturwisa., p.216.
18. A.E. Wilder-Smith, 1970. The Creation of Life. Wheaton, Ill.:
Harold Shaw, p.67.
19. G. Nicolis and I. Prigogine, 1977. Self Organization in Nonequilibrium
Systems. New York: Wiley.
20. I. Prigogine, G. Nicolis, and A. Babloyantz, 1972. Physics Today ,
21. Eigen, Die Naturwiss., p.465.
22. Prigogine, Nicolis, and Babloyantz, Physics Today, p.23-31.
23. Ibid; Nicolis and Prigogine, Self Organization in Nonequilibrium
24. J.C. Walton, 1977. Origins, 4, 16.
25. P.T. Mora, 1965. In The Origins of Prebiological Systems and of Their
Molecular Matrices, p.39.
26. E.R. Harrison, 1969. In Hierarchical Structures. ed. L.L.
Whyte, A.G. Wilson, and D. Wilson, New York: Elsevier, p.87.
27. Nicolis and Prigogine, Self Organization in Nonequilibrium Systems.
28. Eigen, Die Naturwiss., p.465; 1971. Quart. Rev. Biophys.
29. Kaplan, Rad. Environ. Biophysics, p.31.
30. J. Brooks and G. Shaw, 1973. Origin and Development of Living Systems.
New York: Academic Press, p.209.
31. S.W. Fox and K. Dose, 1977. Molecular Evolution and the Origin of
Life. New York: Marcel Dekker.
32. P.A. Temussi, L. Paolillo, L. Ferrera, L. Benedetti, and S. Andini, 1976.
J. Mol Evol 7, 105.
33. S.L. Miller and L.E. Orgel, 1974. The Origins of Life on Earth
Englewood Cliffs, New Jersey: Fn. p. 144.
34. C.E. Folsome, 1979. The Origin of Life. San Francisco: W.H.
35. Temussi, Paolillo, Ferrera, Benedetti, and Andini, J. Mol. Evol., p.105.
36. K. Bahadur and S. Ranganayaki, 1958. Proc. Nat. Acad. Sci. (India)
37. S.W. Fox and K. Dose, 1972. Molecular Evolution and the Origin of
Life. San Francisco: W.H. Freeman, p.142.
38. J. Hulshof and C. Ponnamperuma, 1976. Origins of Life 7,
39. C.N. Matthews and R.E. Moser, 1966. Proc. Nat. Acad. Sci. U.S.
56, 1087; C.N. Matthews, 1975. Origins of Life
6, 155; C. Matthews, J. Nelson, P. Varma, and R. Minard, 1977.
Science 198 622; C.N. Matthews, 1982. Origins of
Life 12, 281.
40. C.N. Matthews, and R.E. Moser, 1967. Nature 215,1230.
41. J.P. Ferris, D.B. Donner, and A.P. Lobo, 1973. J. Mol Biol.
42. J.P. Ferris, 1979. Science 203, 1135.
43. C.N. Matthews, 1979. Science 203, 1136.
44. Katchalsky, Die Naturwiss., p.215.
45. R.E. Dickerson, September 1978. Sci. Amer., p.70.
46. Miller and Orgel, The Origins of Life on the Earth, p.148.