J. theor. Biol. (1997) 187, 483–494
The Origin of Life and its Methodological Challenge
G̈ W̈̈
Tal 29, 80331 Munich, Germany
(Received on 11 June 1996, Accepted in revised form on 3 July 1996)
The problem of the origin of life is discussed from a methodological point of view as an encounter
between the teleological thinking of the historian and the mechanistic thinking of the chemist; and as
the Kantian task of replacing teleology by mechanism. It is shown how the Popperian situational logic
of historic understanding and the Popperian principle of explanatory power of scientific theories, when
jointly applied to biochemistry, lead to a methodology of biochemical retrodiction, whereby common
precursor functions are constructed for disparate successor functions. This methodology is exemplified
by central tenets of the theory of the chemo-autotrophic origin of life: the proposal of a surface
metabolism with a two-dimensional order; the basic polarity of life with negatively charged constituents
on positively charged mineral surfaces; the surface-metabolic origin of phosphorylated sugar
metabolism and nucleic acids; the origin of membrane lipids and of chemi-osmosis on pyrite surfaces;
and the principles of the origin of the genetic machinery. The theory presents the early evolution of
life as a process that begins with chemical necessity and winds up in genetic chance.
7 1997 Academic Press Limited
1. Introduction
2. Inductivism vs. Deductivism
The theory of biological evolution is a historic theory.
If we could ever trace this historic process backwards
far enough in time, we would wind up with an origin
of life in purely chemical processes. The science of
chemistry, however, is an ahistoric science striving for
universal laws, independent of space and time or of
geography and the calendar. This then is the challenge
of the origin of life: to reduce the historic process of
biological evolution to a universal chemical law of
evolution. We can translate this challenge into slightly
different terms. The chemist strives to explain the
inanimate world by reference to mechanistic laws.
The historian strives to understand the world of
human culture by reference to a fabric of plans and
purposes. Chemistry is mechanistic and history
teleological, and the life sciences are the arena where
mechanistic explanation and teleological understanding come into close encounter. Nowhere is this
encounter in sharper focus than in the problem of the
origin of life.
Mechanistic explanation and teleological understanding are two fundamentally different methodologies. In an attempt to unravel this conundrum
we shall begin with the explanatory methodology
of the natural sciences and specifically with the
relationship between theory and experiment, and
more specifically with the inductivist vs. the
deductivist accounts of this relationship. The
methodology of inductivism, as it has long been
held by many scientists, can be summarized as
follows:
0022–5193/97/160483 + 12 $25.00/0/jt960383
(1) Science strives for justified, proven knowledge,
for certain truth.
(2) All scientific inquiry begins with observations
or experiments.
(3) The observational or experimental data are
organized into a hypothesis, which is not yet proven.
(4) The observations or experiments are repeated
many times.
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(5) The greater the number of successful repetitions, the higher the probability of the truth of the
hypothesis.
(6) As soon as we are satisfied that we have reached
certainty in that manner we lay the issue aside forever
as a proven law of nature.
(7) We then turn to the next observation or
experiment with which we proceed in the same
manner.
(8) With the conjunction of all these proven
theories we build the edifice of justified and certain
science.
In summary, the inductivist believes that science
moves from the particulars to the general and that the
truth of the particular data is transmitted into the
truth of the general theory.
Now let me give a summary of Popper’s (1945,
1959, 1963, 1972, 1974, 1983) theory of deductivism:
(1) Science strives for absolute and objective truth,
but it can never reach certainty.
(2) All scientific inquiry begins with a rich context
of background knowledge and with problems arising
within this context.
(3) A scientific problem is hypothetically solved by
a freely invented theory, which explains the
observable by the unobservable.
(4) Competing theories are assessed by their power
to explain many facts with few assumptions.
Experimentally testable consequences are deduced
from the theory and experiments are carried out to
test the predictions.
(5) If an experimental result comes out as
predicted, it is taken as a value in itself and as an
encouragement to continue with the theory, but it is
not taken as an element of proof for the truth of the
theory of the unobservable.
(6) As soon as experimental results come out
against the prediction and we are satisfied that they
are conclusive, we decide to consider the theory
falsified, but only tentatively so.
(7) With this we gain a deeper understanding of
our problem and proceed to invent our next
hypothetical theory for solving it, which we treat
again in the same way.
The concatenation of all these conjectures and
refutations constitutes the dynamics of scientific
progress, moving ever closer to the truth, but never
reaching certainty. In summary, the Popperian
deductivist believes that science moves from the
general to the particulars and back to the general—
a process without end. Let me inject a metaphor.
We might liken the Popperian view of science to
that of a carriage with two horses. The experimental
horse is strong, but blind. The theoretical horse is
lame, but it can see. Only both together can bring
the carriage forward; it leaves behind a track
bearing witness to the incessant struggle of trial and
error.
3. A Metaphysical Research Program
The year 1644 marks the death of a great scientist,
the Belgian physician Jan Baptist van Helmont. He
had spent his life and fortunes on scientific research.
Yet during his lifetime he published nearly nothing
for fear of the inquisition. In his last will he asked his
son to publish his results in the form of a book: Ortus
medicinae (Van Helmont, 1648). It became an instant
success, with translations into several vernacular
languages. It culminated in a most daring thesis: ‘‘All
life is chemistry’’. With this van Helmont established
what Popper would call one of the most sweeping
metaphysical research programs in the history of
science, the problem of the relationship between
animate and inanimate matter. The problems of the
origin of life and of evolution sit squarely within this
research program. This means that we have to
broaden our view to the general relationship between
chemistry and biology.
It was van Helmont who carried out the first
quantitative experiment in the study of the chemical
nature of life and he did it quite methodically. I
present his report in the English translation:
‘‘I took an earthenware pot, placed in it 200 pounds
of earth dried in an oven, soaked this with water, and
planted in it a willow shoot weighing 5 pounds. After
five years had passed, the tree grown therefrom
weighed 169 pounds and about 3 ounces. But the
earthenware pot was constantly wet only with rain . . .
water . . . Finally, I again dried the earth of the pot,
and it was found to be the same 200 pounds minus
about 2 ounces. Therefore, 164 pounds of wood,
bark, and root had arisen from the water alone.’’
Now, what is the methodology behind this experiment? The record is silent on this point. So it would
seem to be legitimate to look at this report through
the spectacles of our current philosophy of science; in
fact alternatively through inductivism and through
Popperian deductivism. We may hope for a double
benefit: (1) a clear understanding of the historic
report; and (2) a clue as to which of the two mutually
exclusive philosophies is right and which is wrong.
Our current state of knowledge tells the inductivist
that van Helmont’s conclusion was wrong. This must
mean to the inductivist that van Helmont did not
     
properly apply the so-called inductive method of
science. Van Helmont does not report any repetitions.
Therefore, the inductivist would have to object that
his experiment should have been repeated with 500
willow trees, or with different kinds of trees, or with
different kinds of soils. And so the inductivist must
come to view van Helmont as one of those queer,
irrational, prescientific characters, amusing but
irrelevant.
Now let us apply the Popperian view of science.
Van Helmont was operating within a rich context of
Renaissance knowledge. It was widely accepted that
matter does not spring from nothing, nor disappear
into nothing. And it was an equally widely held
theory that the substance of growing plants comes
from soil. The first theory was to van Helmont what
Popper calls unproblematic background knowledge.
The second theory was to him problematic and in
need of testing. From both theories jointly he deduced
a testable consequence. The weight gain of a growing
willow tree must be equal to the weight loss of the soil
in which it is rooted. This was a testable prediction.
Van Helmont designed his experiment precisely for
this prediction, bringing the soil before and after the
growth period to the same reference state by drying.
The result was in stark conflict with the prediction.
164 pounds of added tree weight compared with only
3 ounces of loss of soil weight, a small amount well
within the experimental error. In the face of such a
glaring result, van Helmont rightfully decided that
repeating such an experiment would be a waste of
time and money. And so he decided to consider the
soil theory falsified.
Van Helmont operated with a limited set of two
possible material elements: earth and water. Having
eliminated earth, the only remaining possibility was
water. His result then was to him proof by
elimination. This makes it understandable why he
ends his report with a definitive conclusion:
‘‘Therefore, 164 pounds of wood, bark and root had
arisen from water alone’’.
Today we know why this conclusion is wrong. One
of the important nutrients of plants is carbon dioxide,
a gas. Gases, however, were to van Helmont
non-material, spiritual entities. Therefore, by his own
prejudice he was prevented from including gases in his
set of possibilities. It is ironic that it was van Helmont
who discovered that there are gases other than air,
and who coined the name ‘‘gas’’, and who even
discovered carbon dioxide.
There is an important Popperian lesson to be
learned here. In science our sets of possible solutions
should never be taken as exhaustive. They are limited
by the feebleness of our imagination and by our more
485
or less unconscious prejudices. Inductivists have often
missed that simple point.
Here we have now a stark difference between
inductivism and Popper’s deductivism. The inductivists lead us to view science as a gigantic
book-keeping affair and major parts of the history of
science as irrelevant or even ridiculous. By Poppers
account the same history of science is seen as a
fascinating intellectual adventure story and instead of
heaping ridicule on our scientific forebears we see
them for the giants they are.
4. Teleology vs. Mechanism
About 150 years after van Helmont had established
the research program ‘‘all life is chemistry’’ the issue
of chemical-mechanistic explanation vs. teleological
understanding came into full focus. The philosopherscientist Immanuel Kant (1790), at the height of his
fame, entered the ongoing debate about the evolution
of life. He published in his Critique of judgment an
astonishingly sweeping account of the evolution of all
organisms, including man, from a single universal
ancestor and ultimately from dead matter
‘‘It is praiseworthy to employ a comparative anatomy
and go through the vast creation of organized beings
in order to see: if there is not discoverable in it
something like a system, and indeed a system
following a genetic principle. . . . When we consider
the agreement of so many genera of animals in a
certain common schema, which apparently underlies
not only the structure of their bones, but also the
disposition of their remaining parts, and when we find
here the wonderful simplicity of the original plan,
which has been able to produce such an immense
variety of species by the shortening of one member
and the lengthening of another, by the involution of
this part and the evolution of that part, there gleams
upon the mind a ray of hope, however faint, that
something may be done here with the principle of the
mechanism of nature, apart from which there can be
no natural science at all. This analogy of forms, which
in all their differences seem to be produced in
accordance with a common prototype, strengthens
the suspicion of a real kinship by descent from a
common primordial ancestor (Urmutter). This we
might trace in the gradual approximation of one
animal genus to another, from that in which the
principle of ends seems best authenticated, namely
from man, back to the polyp (jelly fish), and from this
back even to mosses and lichens, and finally to the
lowest perceivable stage of nature, to crude matter:
from this and from the forces within, by mechanical
486
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laws (like those by which it acts in the formation of
crystals), seems to be derived the whole technic of
nature which, in the case of organized beings, is so
incomprehensible to us that we feel compelled to
imagine a different principle.
Here the archaeologist of nature is at liberty to go
back to the traces that remain of nature’s earliest
revolutions, and, appealing to all he knows or can
conjecture about its mechanism, to trace the origin of
that great family of creatures, for it must be pictured
as a family if there is to be any foundation for the
noted unbroken coherence of their kinship. He can
suppose that the womb of mother earth as it first
emerged, like a huge animal, from its chaotic state,
gave birth at first to creatures of lesser adapted form,
and that these again bore others more appropriately
adapted to their native surroundings and their
relations to each other; until this womb itself would
have become rigid, ossified and restricted its births to
definite species incapable of further mutation and the
multiplicity of forms was fixed as it stood at the end
of the operation of that fruitful formative force.’’
In a footnote Kant continues: ‘‘An hypothesis of such
kind may be called a daring adventure of reason; and
there may be few, even among the most acute
scientists, to whose mind it would not have sometimes
occurred. For it cannot be said to be absurd, . . . if
certain water animals would mutate step by step into
marsh animals, and from these after some generations
into land animals. In the judgment of plain reason
there is nothing a priori self-contradictory in this. Yet,
experience does not offer an example of it.’’
For appreciating the intellectual context within
which Kant gave this account we have to recall that
Aristotelian philosophy saw the entire universe
permeated with end-means relations (purposes or
final causes), which came to be called ‘‘teleological’’.
Kant restricted the applicability of teleological
judgments to organisms; to their inner organization
and their outer ecological relations and he reduced
their significance to that of mere heuristic, regulative
ideas, imposed on us by the limits of our mind. He
established as the goal of the natural sciences the
replacement of teleological judgments by mechanistic
explanations, but he was a skeptic regarding the
possibility of a comprehensively scientific theory of
evolution. For he did not see how we could ever
explain the origin of life in purely mechanistic terms
and thus avoid attributing to the primordial ancestor
(Urmutter) an organization which was already
directed to the end of all future organisms.
Charles Darwin (1859) and Alfred Russell Wallace
(1858), working independently from each other, but
both being inspired by Thomas Robert Malthus
(1798), must be credited with the monumental
achievement of conceiving for the first time a
mechanism of evolution. They did, however, not
succeed completely in their attempt to replace
teleology by mechanistic explanations. Their theory
neither solved nor even addressed the problem of the
mechanism of the earliest evolution from the
primordial ancestor. Thus, they did not answer
Kant’s skepticism about the possibility of a complete
expurgation of teleology from biology. Indeed,
Darwin (1861) agreed with Kant’s verdict when he
wrote: ‘‘It is mere rubbish, thinking at present of the
origin of life; one might as well think of the origin of
matter’’.
Karl Popper (1965, 1972, 1974) made a major
contribution to theoretical biology by introducing the
problem-solution relation into evolution theory. The
entire process of evolution from the earliest inklings
of life to the highest achievements of science and
technology is seen by Popper as an unended
concatenation of problems and solutions. In the
course of this process of evolution man has become
endowed with the faculty of problem-solution
judgments. By these judgments we understand (and
indeed feel at home in) the world. The importance of
Popper’s approach may be seen in the replacement of
the closedness of the end-means relation by the
openness of the problem-solution relation. Aristotle’s
teleology of final causes corresponds to his static view
of the world. It is incompatible with evolution; and its
remnants within the theory of evolution have always
been justly felt as a foreign element. Karl Popper’s
‘‘situational logic’’ of problem-solution relations is
free of this difficulty. It is a heuristic, regulative idea
in the sense of Kant. But instead of asking with Kant
the Aristotelian question, how the first organism
could have already harbored the means to the ends of
all future organisms, including man, we can now ask
with Popper how the origin of life can be viewed as
the origin of an open, unended concatenation of
problems and solutions. Popper saw the method of
the historians and archaeologists as the method of
hypothetically reconstructing objective problem-solution relations and he suggested that this same
method should also be used by the evolutionist, whom
Kant had called ‘‘archaeologist of nature’’. Popper
made a terminological distinction between ‘‘explanation’’ and ‘‘understanding’’. He reserved the term
‘‘explanation’’ for mechanistic theories and applied
the term ‘‘understanding’’ to the method of
reconstructing objective problem-solution relations.
With this move he created an objective, unified
method of understanding, which applies to the whole
of the history of life.
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5. Two Dogmas of Biology
Kant gave a methodological clue how ‘‘the
archaeologist of nature’’ would have to proceed in
going after the mechanism of the origin of life. He
would have to appeal to all he knows or can
conjecture about the mechanisms of nature. This
brings us back to chemistry. After van Helmont’s
famous thesis: ‘‘all life is chemistry’’, and the later
recognition that plants feed on carbon dioxide and
light while animals feed on plants, it became accepted
to believe that plant chemistry and animal chemistry
are deeply divided, as deeply as they both are divided
from mineral chemistry. In this situation, in the year
1806, Jöns Jacob Berzelius, a Swedish chemist, came
out with two bold conjectures. He held that there is
an essential unity between plant chemistry and animal
chemistry which was called ‘‘organic chemistry’’. This
he distinguished from ‘‘inorganic chemistry’’. But
more importantly, he held that there is an
unbridgeable gap between organic and inorganic
chemistry and that a special force is at work inside all
living beings which was called ‘‘vis vitalis’’. His central
dogma can be formulated as follows:
‘‘The generation of organic compounds from inorganic
compounds in vitro, outside a living organism, is
impossible’’.
The year 1828 marks a watershed in the
relationship between chemistry and biology. Friedrich
Wöhler (1828) published a simple experiment. He
reacted two wholly inorganic compounds, ammonium
chloride and silver cyanate and he produced urea, a
compound which had only been found in the urine of
animals. Wöhler wrote triumphantly in a letter to
Berzelius: ‘‘I can make urea without the necessity of
a . . . dog.’’ He knew, with one single falsifying
experiment he had removed a major gap between
chemistry and biology.
In the year 1913, Walther Löb reported a
remarkable experiment in the spirit of Friedrich
Wöhler. He had subjected a moist, gaseous mixture of
carbon monoxide and ammonia to silent discharges
and found glycine, the simplest amino acid.
Combining this result with the well known interconversion of carbon monoxide and carbon dioxide, he
claimed that he had demonstrated for the first time
the formation of an amino acid, as the simplest
component of natural proteins, from the same
starting materials used by plant photosynthesis:
carbon dioxide, ammonia and water; and with an
energy source which he considered to be closely
similar to light radiation.
487
But Wöhler and Löb had addressed only the
interconversion of inorganic and organic compounds
and claimed it to be the same inside and outside of
organisms. The question of the origin of life, however,
is concerned with quite a different interconversion:
that between inanimate matter and whole organisms.
After their death, organisms are known to turn into
dead, decaying, organic matter. Since antiquity it had
been widely believed that this process is reversible and
that simple organisms, like bacteria, worms or insects,
(even mice by van Helmont’s account), could arise by
spontaneous generation from dead, decaying organic
matter. While Kant and many other scientists saw this
as an absurdity, plain everyday experience seemed to
provide ample evidence. It was not before the year
1861 that the French microbiologist Louis Pasteur
(1862) published his ingenious experiment in swanneck bottles and produced a resounding refutation.
The theory of spontaneous generation of living
organisms was laid to rest. Now biology had its
central dogma:
‘‘The spontaneous generation of whole living organisms
from chemical compounds, outside a living organism, is
impossible.’’
It is the purpose of all inquiry into the origin of life
to refute this dogma.
6. The Myth of the Primordial Broth
In the year 1863 Mathias Jacob Schleiden, one of
the founders of the cell theory, made the first
suggestion toward a mechanistic theory of the origin
of life. He held that a first cell might have been formed
under the entirely different conditions of the young
earth. In 1866, Ernst Haeckel introduced the notion
of a prebiotic broth and two years later Charles
Darwin could no longer resist the temptation to
indulge in what he had earlier called mere rubbish. He
wrote in a private letter, which was published only
much later (Darwin, 1887):
‘‘It is often said that all the conditions for the first
production of a living organism are now present,
which could ever have been present. But if (and oh!
what a big if!) we could conceive in some warm little
pond, with all sorts of ammonia and phosphoric salts,
light, heat, electricity, etc. present, that a protein
compound was formed, ready to undergo still more
complex changes, at the present day such matter
would be instantly devoured or absorbed, which
would not have been the case before living creatures
were formed’’.
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None of these and other early hints can be said to
have great scientific value. They do not give a
mechanism concrete enough to have any explanatory
power, let alone predictive power. They were
components of a very vague metaphysical research
program.
In the early 1920s the Communist party of the
Soviet Union is said to have come to the conclusion
that its atheistic campaign would be bolstered, if it
could be shown ‘‘scientifically’’ that the origin of life
did not require a divine intervention. And so, as
intimated by Christian de Duve (1991), it was
Alexandr Ivanowitsch Oparin (1924), the biochemist
and later Lysenkoist, who took it upon himself to
produce such a theory. It was produced and published
in 1924. This was a brave attempt to replace teleology
by mechanism. But it had fundamental flaws.
Objectively speaking, Oparin’s theory incorporated
many of the earlier suggestions about a prebiotic
broth. By Popper’s standards Oparin’s theory should
have departed from these vague beginnings by going
in the direction of greater concreteness. This would
have generated explanatory power, as well as
predictive power, which means testable, falsifiable
consequences. But this is precisely what did not
happen. Oparin’s primary impetus was political. He
strove for convincing power. And so he designed his
theory to be immune against criticism or falsification
by admitting a large variety of organic compounds
into the prebiotic broth. This basic vagueness was not
corrected by the other men who published early
papers after Oparin, notably the Marxists J. B. S.
Haldane (1929), who had given the theory its name,
and J. D. Bernal (1949), who added the notion of clay
adsorption. The theory remained vague and
untestable, and so it remained untested for 30 years.
The situation improved somewhat when Harold C.
Urey (1952) published his theory that the primordial
atmosphere of the earth consisted mainly of methane
and ammonia. It followed that the prebiotic broth
must have been stocked with the compounds which
are formed when lightning strikes such a primordial
atmosphere. It was only then that a portion of the
theory of a prebiotic broth became definite enough to
come into reach of a new kind of experiment. Stanley
L. Miller (1953, 1955), a student of Urey, carried out
the test: electric discharges in a moist, gaseous
mixture of methane and ammonia. He produced
mostly a brown tar, but also, amazingly, significant
amounts of glycine and other amino acids.
Now the science community made what some may
call an inductive inference. From something experimental and observable they inferred something
historical and unobservable: The prebiotic broth
contained amino acids. Amino acids alone cannot
make an organism. Many other components are
needed: purines, pyrimidines, sugars, lipids and
coenzymes. In the next 40 years numerous Miller-style
experiments were carried out [for a review see de
Duve (1991); Maynard Smith & Szathmáry (1995)].
The conditions were modified with the aim to
generate some of these other components. As soon as
traces of another compound were found, this too was
claimed to have been in the prebiotic broth. In this
way the broth became stronger and stronger, but the
theory became weaker and weaker. The physicist
Manfred Eigen and co-workers (1981) proclaimed
that he had no doubt that the prebiotic broth
contained all kinds of biomolecules and that it was
something like a nourishing beef tea. And Alan
Weiner (1987) wrote in a standard textbook of
molecular biology: ‘‘Indeed, it would not be an
exaggeration to say that every expert in the field of
molecular evolution has a different notion of what
exactly was in the prebiotic soup’’.
The situation grew still worse. Some of the
supposed ‘‘prebiotic’’ reactions require chemical
conditions which are incompatible with the conditions of others. Therefore, it was concluded that
there must have been several separate cauldrons with
prebiotic broth, with different chemical conditions
(Shapiro, 1986) Others claimed that the soup was
significantly enriched with organic meteor or
cometary material (Oro, 1961) or unknown ingredients from interstellar dust grains (Chyba & Sagan,
1992). Others speculated that the prebiotic broth
would wind up on hot volcanic rocks, polymerize and
then be taken up by rain (Fox & Dose, 1977). If we
check this situation against Poppers methodology of
science we can make three observations:
(1) With every modification the prebiotic broth
theory increased in vagueness and ambiguity and
it decreased in explanatory power and falsifiability.
This development of the theory was counterscientific.
(2) Most workers in the field were inductivists.
They believed that the sum total of the experimental
results would tell us all about the prebiotic broth.
There is perhaps no other example in the whole of
science which violates the principles of Popper’s
methodology of science more thoroughly. And there
seems to be no other scientific enterprise, which has
suffered a similar devastation from the attitudes of
justificationism and inductivism, as the prebiotic
broth theory. It is a perfect example for the
consequences of a continued application of the wrong
methodology of science.
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(3) All these prebiotic broth experiments utterly
failed to ‘‘induce’’ a coherent picture of the earliest
mechanisms of life. This conceptual incoherence was
rationalized by a sweeping appeal to chaos and
chance. And with this was buried any hope for finding
the long sought mechanism of the origin of life. Not
even the RNA-world theory with its fruitful
experimental program is here an exception.
It must be admitted that many scientists have been
very successful without ever thinking about the theory
of knowledge. Others have been philosophical
inductivists, but in their scientific practice—quite
inconsistently—deductivists. In the face of our
complex problem we cannot hope to succeed with any
form of inductivism.
7. Biochemical Retrodiction
We shall now leave these historic reflections and
turn to the application of Popper’s methodology of
science. It will be shown how Popper’s situational
logic of problem-solution relations can serve as a
heuristic guide to generate a mechanistic theory on
the origin of life; and how we can monitor our
progress in theory building, first pre-experimentally
by applying Popper’s principle of explanatory power,
and later by experiments.
The problem of the origin of life is about entities
which are irretrievably unobservable because they
existed in the past. Therefore, this problem can clearly
be solved only by a theory. Scientific theories have
consequences. If the consequences are new we speak
of experimentally testable predictions. If the consequences are known we speak of explanations. Turning
first to the question of testing predictions we note that
a theory on the origin of life, even though historic in
character, can be tested by virtue of the chemical
mechanisms it entails. Now, but by the laws of
classical logic a positive outcome of such an
experiment can never be taken as an element of proof
of the truth of the theory. It is, however, logically
possible to conclude from a negative result that our
prediction is false and that, therefore, our historic
theory must also be false. For this reason experimental programs should be set up in such a way that
negative results can be taken as being conclusive.
A meaningful experimental program of this kind in
the field of the origin of life is very costly. Therefore,
it would be unwise to embark on experiments without
a previous comprehensive attempt to criticize or even
(at least partially) falsify the theory on strictly
theoretical grounds. Logical consistency and compatibility with the laws of physics and chemistry (e.g.
489
thermodynamics) are important checks. But the most
important tool for evaluating theories appears to be
Popper’s ‘‘principle of explanatory power’’. It
stipulates that a modification of a theory should lead
to an increase in explanatory power, i.e. to the
explanation of more facts with fewer assumptions. In
the case of theories on the origin of life explanatory
power can only be established by relating biological
facts that exist today with explaining assumptions
that go back some four billion years. This is one of
the main challenges.
It is clear that the principle of explanatory power
is closely related to the problem of constructing a
theory. It is here suggested that the construction of a
theory on the origin of life may be best approached
by using problem-solution relations as a heuristic
guide (as a regulative idea). Biologists and biochemists frequently speak of the function of an organ
within an organism or of a constituent of a
metabolism. It is important to realize that ‘‘function’’
is a teleological term and that its meaning is
coextensive with the meaning of the term ‘‘solution of
a problem’’ in Popper’s situational logic. The task of
establishing the mechanism of early evolution may
therefore be guided by a method of reconstructing
a
concatenation
of
problems
and
solutions, which means reconstructing evolutionary
precursor functions to extant biochemical functions
(Wächtershäuser, 1987, 1992). In this effort the
principle of explanatory power can be intuitively
satisfied, if we select those reconstructions by which
one precursor function gives rise to two or several
successor functions. The application of the principle
of explanatory power shall now be demonstrated
for three topics within the theory on the chemoautotrophic origin of life (Wächtershäuser 1988a, b,
1990, 1992 1994).
8. Surface Metabolism and the Basic Polarity of Life
All extant organisms are cellular. Cellular organization has the function to keep all constituents of the
metabolism together for interaction. But cellular
organization is paradoxical: what keeps constituents
efficiently in, keeps food efficiently out. Therefore,
cellular organization requires complex transport
systems. This is the reason for the need to postulate
a functional precursor. The only functional precursor
which avoids the paradox seems to be a sufficiently
strong bonding of all constituents to a mineral
(surface metabolism).
The proposed strong bonding to mineral surfaces is
not only the functional precursor of cell enclosure;
but through catalytic mineral effects also the
490
. ̈̈
functional precursor of enzyme surfaces. Moreover,
the stabilization of peptides by bonding to mineral
surfaces can be seen as the evolutionary precursor of
protein stabilization by internal folding. This
provides, quite importantly, an explanation for the
possibility of a hyperthermophilic origin of life (which
is evidenced by the hyperthermophilic nature of the
last common ancestor in conjunction with the
proposed thermal irreversibility of evolution). More
generally speaking, in a surface metabolism the
reactions are inflicted with much smaller reaction
entropies than in a solution metabolism. This means
that mineral bonding can to some extent be seen as
the functional evolutionary precursor of energy
coupling mechanisms in extant metabolisms.
It should be noted that in the above evolutionary
precursor-successor relations the teleological treatment is readily turned into a mechanistic treatment if
we go to the molecular level. Additional mechanistic
consequences of mineral bonding come into view,
when we consider that for achieving these functions
the mineral bonding must be very strong. According
to the rules of Paneth and Fajans only the bonding
of negatively charged, anionic, organic constituents to
positively charged, cationic mineral surfaces is strong
enough (Wächtershäuser, 1988b). This gives a general
dual selection rule in terms of minerals and
constituents for reconstructing the primordial metabolism (Wächtershäuser, 1988b) This dual selection
rule has recently been successfully applied in the
mineral-implemented polymerization of anionic
amino acids (Glu, Asp) and nucleotides (Ferris et al.
1996; von Kiedrowski, 1996). And it provides a
number of additional explanations. It explains why
the lipid membranes of extant cells are anionic on the
inside; and why most of the constituents of the extant
central metabolism are anionic; and notably why the
central sugar metabolism involves anionic phosphorylated sugars: the phosphate groups served
originally as surface bonding mediators. Only the
simplest of all sugars, glycol aldehyde (OHC-CH2OH) is non-phosphorylated in the extant metabolism.
Therefore, the theory of surface metabolism postulated a surface-bonded, phosphorylated glycol
aldehyde (OHC-CH2-O-PO23 − ) as the functional
precursor of extant glycol aldehyde and the formation
of phosphorylated pentoses by the surfacemetabolic condensation of phosphorylated glyceric
aldehyde and phosphorylated glycol aldehyde
(Wächtershäuser, 1988b, figs 4 and 13, p. 472). This
surface-metabolic prediction has recently been
confirmed (Pitsch et al., 1995).
This crucial consideration of the theory of surface
metabolism has been summed up by the thesis:
‘‘The primordial organisms had a two-dimensional
metabolic organization.’’ (Wächtershäuser, 1988b).
The theory of surface metabolism has another
far-reaching consequence. Minerals, notably pyrite,
have the property of undergoing facile secondary
nucleation. This is seen as the oldest form of division
and the inorganic place holder of cell division. It is,
therefore, beneficial to distinguish three forms of
reproduction: (1) organizational reproduction beginning with secondary nucleation and ending in cell
division; (2) metabolic reproduction of a food
acceptor as in the proposed archaic reductive citrate
cycle; and (3) genetic reproduction, which conventionally is termed ‘‘replication’’. By the logic of the
theory of a chemo-autotrophic origin of life,
organizational reproduction may be seen as preceding
metabolic reproduction, which in turn brings forth
genetic replication.
9. The Origin of Chemi-osmosis
All non-parasitic bacteria and archaea embody a
fundamental division of labor. The exergonic
chemi-osmotic machineries (of chemotrophs as well
as phototrophs) generate chemical potentials (e.g.
ATP) for driving the endergonic metabolism.
Chemi-osmosis is dependent on closed cell membranes and thus too complex to be primordial. This
calls for the construction of a functional precursor. It
can be constructed by appealing to steps of energy
conservation in the form of thioester group activation
within the metabolism. Christian de Duve (1987) has
made the important proposal that thioesters constitute the primordial energy source of life (albeit within
the context of the soup theory). The theory of a
chemo-autotrophic origin of life postulates that
thioester group activation has a still more simple
functional precursor in thioacid group activation
(Wächtershäuser, 1988a); and that thioacids are
formed
by
kinetic
coupling
mechanisms
(Wächtershäuser, 1992, 1993, 1994). It has been
experimentally corroborated that thioacetic acid
(CH3COSH) is formed as predicted (a) from CO and
methyl mercaptane, which is itself producible from
CO and H2S/H2 in the presence of NiS/FeS (Huber &
Wächtershäuser, 1997); and (b) from thioglycolic acid
(HSCH2COOH) with the pyrite-forming redox energy
source FeS/H2S (Keller et al. 1994). Both of these
reactions rely on the involvement of mineral sulfides
of transition metals. These are known to have the
positive surface charges required for a surface
metabolism—another case of explanatory power.
Before we can address the emergence of chemi-osmosis we have to consider briefly the emergence of closed
     
cell envelopes. The conversion of thioacetic acid from
thioglycolic acid has been postulated to proceed
through a carbanionic intermediate (−CH2-COSH),
which has been predicted to undergo condensations,
and notably Claissen condensations (Wächtershäuser,
1993), which recursively will produce fatty lipids.
Alternatively, the first Claissen product is predicted to
undergo a second type of condensation to form the
thioacid form of 3-hydroxy-3-methyl-glutarate
(HSOC-CH2-C(OH)(CH3)-CH2-COSH), which turns
into the thioacid of methyl-glutaconate (HOOC-CH2C(CH3).CH-COSH), which is a vinylogous form
of malonyl-CoA, and therefore has been postulated
to form isoprenoid acid lipids (Wächtershäuser,
1992). This is another example of explanatory
power.
We are now ready to consider the emergence of
chemi-osmosis. As a point of departure we assume a
surface metabolism on pyrite surfaces, wherein all
redox reactions are local reactions [Fig. 1(a)]. Next we
assume a delocalization of some redox reactions,
whereby an electron source site of pyrite formation is
separated from an electron sink site of, say, hydrogen
formation [Fig. 1(b)]. The electrons are transported
from the source site to the sink site either through the
semiconductive pyrite crystal or through anionically
surface-bonded iron-sulfur clusters, which are at first
strictly inorganic (with sulfide-ligands). The earliest of
these clusters are assumed to form two-electron
transport chains, involving intermediate disulfido
ligands. With the emergence of amino acids and
(Cys-containing) peptides the two reaction centers
and the electron transport chain become ligandmodified (more selective and accelerated). The
electron source is now a hypothetical oxidase,
converting the S−-units of FeS to S22 − -units of FeS2;
and the electron sink is a reductase, e.g. a
hydrogenase, forming H2.
Next we assume the formation of a closed lipid
membrane around the pyrite mineral; and we assume
further that the lateral electron flow along the inside
of a closed lipid membrane becomes coupled to
reciprocating conformational changes of a protein
structure, causing cyclical conformational changes of
a membrane-spanning protein, with the effect of
proton pumping through the membrane from the
outside to the inside [Fig. 1(c)]. This will have the
positive feedback effect of allowing the organism to
survive in spaces with a high pH. This functional
advantage takes effect as soon as the rate of active
proton pumping into the cellular structure will
outpace the passive equilibrating flux of protons.
Now the cellular organism can colonize hitherto
uninhabitable pH-spaces.
(a)
491
H2
+ Fe-SH + H S
2
2 H+
+ Fe-S-SH + 2H +
FeS 2
(b)
H2
2 H+
+ Fe-SH + H S
2
e+ Fe-S-SH + 2H +
FeS 2
(c)
H2
2 H+
H+
+ Fe-SH + H S
2
e+ Fe-S-SH + 2H +
FeS 2
(d)
H2
2 H+
H+
e-
2 HSSS-
+ Fe-S-SH + 2H +
FeS 2
(e)
H2
2 H+
+ Fe-SH + H S
2
H+
e-
2 HSSS-
F. 1. Hypothetical scheme of the early evolution of
chemi-osmosis.
Next we assume that the cyclical thiol-dithio
conversion, (2 HS-t-S-S-) becomes coupled with the
pyrite-forming center [Fig. 1(d)], and that the cell
membrane will harbor a whole population of this
system. Later, some of these may be subject to flow
reversal. The hydrogenase then takes up dihydrogen,
while polysulfides (and later sulfur) are reduced to
disulfide for pyrite formation (and later to H2S). Still
later other terminal reductants and oxidants can
become operative. If the Gibbs free energy of one of
the reversed redox flows is not sufficient, it can be
boosted by the passive flux of protons from the inside
to the outside, driven by the proton gradient that is
created by the non-reversed systems.
As the next stage we consider that the organism
encounters a chemical environment, in which a
reversed redox flow has a high negative Gibbs free
energy of reaction. By this energy source protons are
492
. ̈̈
now pumped actively from the inside to the outside
to create a reverse proton gradient [Fig. 1(e)]. This is
the situation of the proton pump of Methanobacterium thermoautotrophicum, which is driven by the
reduction of heterodisulfides with molecular hydrogen (Setzke et al. 1994; Hedderich et al., 1994). This
reversed gradient will now cause a passive proton flux
from the outside to the inside. It will at first be in
service of boosting redox reactions. Later it will
energize a membrane pyrophosphatase (cf.
Baltscheffsky et al., 1986); and still later an ATPase.
At a still later time the membrane becomes endowed
with a population of laterally diffusible quinone lipids
as an electron pool. And much later still, phototrophy
begins in the bacteria by the photo-boosting of a
pre-established electron flow, and in the archaea as a
supplementary proton pump.
The above evolutionary account has been drawn up
on the basis of the principle of explanatory power as
a multi-step functional succession, which begins with
an internal lateral electron flow. It should be
compared to the possibility of a single-step theory,
which assumes an electron flow through the
membrane from the start (Koch & Schmidt, 1991).
On the Functional Roots of the Genetic Machinery
The genetic machinery is of great importance. Its
DNA sits in the cell like the queen in a bee hive. How
did this enthronement occur? Two functions are of
central importance to the workings of the genetic
machinery: replication and translation. We can
therefore ask: which of these two functions has
evolutionary priority? All those, who see sequence
‘‘information’’ as the ‘‘essence’’ of life, have given
replication priority over translation and defined a
replicating RNA molecule as the first form of life
(Weiner, 1987). This line of thinking is now widely
known as the ‘‘RNA-world theory’’. If by contrast we
adopt a strictly chemical orientation, we treat nucleic
acids simply as catalysts. They are catalytic in a dual
sense. They catalyse their own formation (replication)
and they catalyse the formation of enzymes
(translation) which in turn catalyse the metabolism.
By a simple generalization we may recognize that the
earliest functional precursor of the genetic processes
must be seen in organic byproducts of the metabolism
exerting a dual catalytic feedback function: for the
metabolism and for their own pathway of derivation
from said metabolism. As soon as such a dual catalyst
(vitalizer) is formed de novo, it will persist by virtue
of its own catalysis. This then is the first form of
inheritance by a strictly kinetic effect. All extant
coenzymes are examples of such vitalizers. With the
appearance of every new vitalizer a new dual feedback
loop becomes grafted onto the pre-existing metabolism. The metabolism is, therefore, self-expanding;
and the nucleic acids are seen as its late expansions,
as glorified coenzymes. And this process of genetic
expansion may be seen with Noam Lahav (1991) as
a coevolution of translation and replication.
From the vantage point of a surface metabolism the
earliest precursor function of nucleic acid bases has
been seen as acid-base catalysis of imidazole-type
bases, giving rise later to the base pairing functions.
The earliest function of the phosphate groups has
been seen in surface-bonding mediation; giving rise
later to the functions of backbone connectors and
replication activation. The earliest precursor of the
phospho-ribose backbone has been seen in a
backbone of surface-bonded phosphotrioses, interconnected by a hemiacetal backbone and carrying
bases for catalysis and later for translation
(Wächtershäuser, 1988a). This proposal can now be
extended owing to Albert Eschenmoser’s (1994)
ingenious proposal of a pyranosyl-RNA. This would
be the stage in which replication first emerged and
furanosyl-RNAs and -DNA would have been the
ultimate heirs of this evolution.
It may be noted that the teleological term
‘‘information’’ is no longer required nor helpful for
the description of this earliest genetic mechanism. On
the level of nucleic acid sequences it is quite
convenient to use the information metaphor. We
should, however, recall that in information theory we
distinguish ‘‘digital information’’ and ‘‘analog information’’. Quite formally, we could then say that
analog information is the functional precursor of the
digital information of nucleic acid sequences. But as
soon as we try to give concrete meaning to the term
‘‘analog information’’ we recognize that it is nothing
more than the dual catalytic feedback described
above. This is a good example for the nature of the
method of biochemical retrodiction. We begin with a
complex situation to which we apply teleological
notions such as function or information. We then
reconstruct a precursor function (or a precursor
information). But in the course of this very process of
retrodiction the teleological notions, whence we
started, fade away. And what remains is a purely
chemical mechanism.
Conclusion: A Popperian World of Problems
Theories of evolution have a certain complexity.
The theory of the chemo-autotrophic origin of life is
no exception. It is actually a Popperian research
program, harboring a plurality of parallel theoretical
     
lines which are at first only loosely connected. The
development of this program under the guidance of
the principle of explanatory power drives towards
unification. For precursor functions are by this
principle constructed as the common precursors of
several disparate successor functions. This creates the
theoretical image of an origin of life in a deterministic
chemical mechanism, which increases in complexity
by a process of self-expansion, which means an
unfolding of the possibilities. Evolution is then seen
as beginning in necessity and winding up in chance.
In the earliest phases of this overall process of
evolution the notion of biological selection is not
required or even meaningless. It comes into play only
later, after the invention of genetic isolation, and it
has the function of keeping the explosion of
possibilities at bay.
The process of evolution has now been going on
since some four billion years. It begins with a form of
life which we may now hope to be able to explain in
purely mechanistic terms: as a simple process of
reproduction (like the reductive citrate cycle), feeding
on simple inorganic nutrients, like CO2, CO, NH3,
N2, H2S, H2Se, PO34 − , MoS24 − , WS24 − , FeS, NiS, CoS,
MnS, ZnS, in a hot aqueous environment of
magmatic exhalations. Wherever these conditions are
right we should find the original homestead of life; the
‘‘iron-sulfur world’’ of an Ur-organism that exists
without problems and may therefore be considered
barely alive. Therefore the origin of life is not a point
in time. It is a point in space. From this vantage point,
evolution is primarily a spatial affair, time coming in
by virtue of the history of the conquering of space.
It would seem beneficial to look at that great chain
of evolution from the Popperian point of view of an
evolution of problems. The first ‘‘problem’’ is that of
the survival in conquered neighboring spaces and the
first ‘‘solutions’’ are expanded forms of the metabolism—expanded by dual feedback loops which are
anastrophes in the sense of Herric Baltscheffsky
(1977). Each of these earliest spatial varieties of life
is in chemical harmony with its environment and in
this sense chemically adapted. And all metabolic
innovations must be seen as being in a state of rapid,
global exchange. This is the basis for the biochemical
unity of life. With the evolutionary invention of
genetic isolation mechanisms we begin to see
differently endowed organisms, faced with the
problems of competing for the same resources. This
is the beginning of biological selection as postulated
by Darwin and Wallace.
Looking finally at the extended sweep of a
Popperian evolution of problems, we may adopt
Popper’s distinction between long- and short-range
493
problems. Long-range problems find their solutions
genetically (first by simple dual feedback loops and
later by the help of selection). It is within this basal
layer of evolution, that we find the emergence of a
solution of the ultimate long range problem: how to
solve short range problems. The solutions are seen in
mechanisms of perceptional control, which in their
earliest forms of chemotaxis and phototaxis are seen
as deriving from and feeding back into the nutritional
requirements of the organisms (Wächtershäuser,
1987). While themselves clearly the product of genetic
evolution, these machineries allow organisms to solve
the problems that come and go during their lifetime.
Now the organisms loose their problem blindness.
With the emergence of the central nervous systems
comes the next great leap. The emergence of
consciousness, which is fundamentally problem
awareness. The so far ultimate leap is the linguistic
revolution. Hitherto unembodied and only subjectively felt problems can now be linguistically
embodied and thus objectivated. This is the
foundation of human culture with its towers of
complexity, so high that we may never hope to reach
the level of full mechanistic explanation; and thus are
forced to be contented with that great and precious
faculty of understanding, with which we have become
endowed by evolution: our faculty of teleological
judgment.
The present paper and my earlier work would not exist
without the inspiration by the late K. R. Popper. I benefited
from discussions with R. Hedderich, O. Kandler, D.
Seebach, R. K. Thauer & H. Weiss. Experimental work
(Huber & Wächtershäuser, 1996) was supported by the
Deutsche Forschungsgemeinschaft.
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