Marine Biological Laboratory
Rp^^iveH July 5> 1958
Accession No._Z?Z^
r- D Academic Press, Inc.
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THE ORIGIN OF LIFE
ON THE EARTH
THE ORIGIN OF LIFE
ON THE EARTH
A. I. OPARIN
ACTIVE MEMBER OF THE ACADEMY OF SCIENCES
OF THE U.S.S.R.
THIRD REVISED AND ENLARGED EDITION
Translated from the Russian
by
ANN S YN GE
ACADEMIC PRESS INC., PUBLISHERS
NEW YORK • 1957
I
OLIVER & BOYD LTD.
Tweeddale Court, High Street
Edinburgh i, Scotland
Edition for all of the Americas, except Canada
Published by
ACADEMIC PRESS INC.
Ill Fifth Avenue
New York 3, New York
ALL RIGHTS RESERVED
This book may not be reproduced by
any means, in whole or part, without
the written permission of the Publishers
PRINTED IN GREAT BRITAIN
AT THE CENTRAL PRESS (ABERDEEN) LTD.
FOR OLIVER AND BOYD LTD., EDINBURGH
PREFACE
My FIRST WORK on the origin of life was published
as a small booklet in 1924 {Proiskhozhdenie zhizni.
Moscow: Izd. Moskovskii Rabochii). In it I for-
mulated, though very schematically, the essentials of this
problem.
I explained these propositions in an expanded form in my
book Vozniknovenie zhizni na zemle [The origin of life on the
Earth) (Moscow: Izd. AN SSSR), the first edition of which
was published in 1936. The second edition was published
in 1941 without substantial alteration.
After a lapse of 20 years there has accumulated a very
large amount of factual material bearing on the origin of life
derived from various fields of scientific endeavour. This
allows us to draw a considerably more definite picture of the
successive stages in the development of matter on the way
to the origin of life.
The 1941 edition of the book has, accordingly, been thor-
oughly revised in the light of this new factual material. The
only important features which have been retained from the
earlier editions are the fundamental ideas and propositions.
I wish to express my profound thanks to Professors N. M.
Sisakyan, A. G. Pasynskii, A. N. Belozerskii, V. L. Kretovich
and G. A. Deborin for looking over particular chapters of the
book and for their valuable criticisms and advice, and also to
all my colleagues in the A.N. Bach Institute of Biochemistry
of the Academy of Sciences of the U.S.S.R. who have helped
me in my work on this edition.
I wish also to make special recognition of the hard and
valuable work expended on this task by Candidate in Bio-
logical Sciences N. S. Gel'man.
Vi PREFACE
In connection with the English language edition of the
book I should like to extend my hearty thanks to Mrs. Ann
Synge for her work in translating it and also to the publishers,
Messrs. Oliver and Boyd.
A. Oparin
16.10.56.
:oS
TRANSLATOR'S PREFACE
\ pi.
THIS BOOK is a complete translation of the text of the
third and completely revised edition of Professor
Oparin's book, although some of the illustrations have
been left out. The Russian and English editions should
appear more or less simultaneously. The first edition was
translated into English by Professor Sergius Morgulis and
was published under the title The origin of life by the
Macmillan Company (New York, 1938). It was reprinted by
Dover Publications Inc. (New York, 1953).
I could not have undertaken this translation unaided and
have received much help from many sources. My husband
has helped at all stages. In particular, he has dealt with the
bibliogTaphy and checked the spelling of all proper names
which had to be transliterated from the Russian alphabet.
He writes: "Transliteration of Russian names is by the
system used in Chemical Abstracts (see annual author index).
Titles of periodicals have been abbreviated, in general, as
in the World list of scientific periodicals published in the
years ipoo-ip^o (London (Butterworth Scientific Publica-
tions), 1952). However, for most Russian journals the ab-
breviations are as in Chemical Abstracts (see indexes for 1951
and 1956) ; these will be found as good, or better, for tracing
the periodicals in the World list itself. Alternative trans-
literations of the names of authors are given in brackets where
this seems bibliographically helpful. Where the author cites
Russian review articles and books I would like to have
included supplementary references to works more accessible
to English readers, but circumstances have prevented me
from doing this in more than a few instances. In connection
with verifying the references I am grateful for their unstinted
help to many librarians, and especially to the staffs of the
Reid Library, Bucksburn, and of the Library of the Uni-
versity of Aberdeen."
I have also received advice and help from Mr. N. W. Pirie,
who read the typescript, and from Dr. H. Lees and Mr.
VU
viii translator's preface
M. V. Tracey who read the proofs. My technical and ter-
minological advisers are in no way responsible for the views
expressed in the book. I hope their, perhaps unconscious,
attempts to use it as a platform for their own scientific views
have not distracted me from an accurate presentation of
Professor Oparin's ideas. He has, in any case, checked the
translation in detail from beginning to end.
The following illustrations are reproduced by courtesy of
the authors and publishers cited: nos. 4 and 5, McGraw-Hill
Book Co. Inc.; no. 10, the Director of Lund Observatory, on
behalf of the late Dr. W. Gyllenberg; no. 20, Prof. Linus
Pauling and the National Academy of Sciences of the U.S.A.;
nos. 23 and 24, Prof. G. Schramm and the Editors of Nature;
no. 25, Dr. F. H. C. Crick and the Editors of Nature; no. 26,
the Publisher of The Scientific American; nos. 31 and 32, the
Wistar Institute of Anatomy and Biology ; no. 34, Dr. M.
Yeas and the National Academy of Sciences of the U.S.A.;
no. 35, the Springer-Verlag, Vienna; nos. 38, 39, 41, 42, 43
and 44, the Academic Press Inc.
My thanks are due to all those I have mentioned and to
my teacher, Mrs. Vera Raitt, who has helped me in my
struggles with the Russian language, as well as to many others
who have helped with typing, illustrations, references and
other matters, not forgetting the publishers, Messrs. Oliver
and Boyd, who have made strenuous efforts to get the book
out in time for the first international Symposium on the
Origin of Life, organised by the Academy of Sciences of the
U.S.S.R. under the auspices of the International Union of
Biochemistry.
Ann Synge
Aberdeen,
April 1957.
INTRODUCTION
The question of the emergence of Ufe, of the origin on the
Earth of the first hving things, raises a number of important
and fundamental problems of natural philosophy. Every
man, whatever his stage of development, has, consciously or
unconsciously, put this question to himself and found some
sort of answer to it, for without some such answer one cannot
form even the most primitive picture of the world.
History shows that the problem of the emergence of life
has fascinated the human mind from time immemorial.
There has been no religious or philosophic system and no
great thinker that has not devoted serious attention to this
problem. In different epochs and at different stages of cul-
tural development the question of the origin of life has
been answered in different ways. This problem has however
always been the focus of a bitter conflict of ideas between
two irreconcilable schools of philosophy — the conflict between
idealism and materialism.
At the beginning of our century this conflict did not merely
fail to abate but took on a special bitterness because, although
science had already achieved glittering and dizzy successes in
many fields, it seerned unable to give a rational, scientifically
based answer to the question of the origin of life. It appeared
that a dead end had been reached as far as this problem was
concerned.
Such a state of affairs was by no means fortuitous. It may
be explained as follows. About a century ago almost every-
body held that the principle of spontaneous generation
prevailed so far as the origin of life was concerned. They
were convinced that living things could originate, not only
from others like themselves, but that they could also come
into being spontaneously, appearing all at once, fully formed
and organised, among inanimate objects.
Both idealists and materialists held this point of view.
The only point of dispute was : what was the cause and what
the nature of the forces determining this coming into being.
ix
X INTRODUCTION
According to the idealistic way of thinking all living
things, including human beings, originally came into being
in more or less the same form in which we now see them,
owing to the effect of supernatural spiritual forces, that is to
say as the result of a creative act by a deity, formative origin-
ating spirit, life force, entelechy or some such concept. In
other words, they arose as the result of the influence of a
primary spiritual cause which was, itself, according to the
idealists, the essence of life.
In opposition to this, the materialistically minded scientists
and philosophers set out from the premise that life is material
in nature like everything else in the world, and that no
spiritual force need be invoked to explain its origin. As most
of them accepted spontaneous generation as a fully confirmed
' fact ', they had to explain it as the result of the action
of natural laws, while denying the intervention of any
spiritual force whatever. It seemed to them that the most
direct approach to a solution of the problem of the origin
of life was to find in nature, or produce in the laboratory,
instances of spontaneous generation, and to study the pheno-
menon by all the available scientific methods.
However, very accurate observations and experiments,
especially the researches of Louis Pasteur, demonstrated con-
clusively the illusory nature of the very ' fact ' of the spon-
taneous generation of even the most primitive organisms
from inanimate material. It was established with complete
certainty that all previous reports of the occurrence of spon-
taneous generation had been the fruit of errors of method,
incorrect setting up of experiments or superficial interpreta-
tion of them.
This removed the ground from under the feet of those
students of nature who saw spontaneous generation as the
only conceivable way in which life could have arisen. After
Pasteur they lost all possibility of an experimental approach
to the solution of this problem and this led them to form
very pessimistic conclusions and to assert that the problem
of the origin or life was * accursed ' and that it was an
insoluble question unworthy of the work of any serious
investigator and to study it would be simply a waste of his
time.
INTRODUCTION XI
This led to a serious crisis in the ideas of many scientists
of our century concerning the problem with which we are
dealing. Some of these scientists tried to get out of the
question by suggesting that life never arose on Earth but that
the first living things were brought here from somewhere
else such as the surface of one of the nearer or more distant
planets. Others got round the question of the origin of life
by adopting openly idealistic positions and declaring that
the problem belonged, not to the province of science but to
that of faith.
It was, of course, not the nature of the problem which led
to this crisis but the fact that scientists were using faulty
methods in their approach to it.
It was the outstanding service of Charles Darwin to biology
that he broke with the earlier metaphysical methods for attack-
ing the problem of the origin of the existing forms of animals
and plants. He showed, beyond question, that highly organised
living creatures can appear on the Earth only as the result
of prolonged development, that is, evolution of higher forms
from lower ones. In the absence of such evolution it was
impossible to maintain that human beings or other highly
developed organisms had arisen by natural means without
the intervention of any spiritual or supernatural agency.
However, even after Darwin's work, scientists approached
the problem of the origin of the very simplest living things,
which were the first ancestors of every living thing on Earth,
in the same metaphysical way which had prevailed in regard
to more highly organised organisms before Darwin's time.
We have, however, already seen that, even after the work of
Darwin, people tried to explain the origin of life by separ-
ating it from the general development of matter. They
regarded it as a sudden act of spontaneous -generation of
organisms which, though themselves primitive, were still
endowed with all the complicated attributes of life. This
approach to a solution of the question was, however, found
to be radically inconsistent with the results of experiment
and observation and could therefore lead to nothing but
bitter disappointment.
A completely different prospect opens out before us if we
try to approach a solution of the problem dialectically rather
Xll INTRODUCTION
than metaphysically, on the basis of a study of the successive
changes in matter which preceded the appearance of life and
led to its emergence. Matter never remains at rest, it is con-
stantly moving and developing and in this development it
changes over from one form of motion to another and yet
another, each more complicated and harmonious than the
last. Life thus appears as a particular very complicated form
of the motion of matter, arising as a new property at a definite
stage in the general development of matter.
As early as the end of last century Frederick Engels indi-
cated that a study of the history of the development of matter
is by far the most hopeful line of approach to a solution of
the problem of the origin of life. These ideas of Engels were
not, however, reflected to a sufficient extent in the scientiftc
thought of his time.
Even in the first decades of this century only a very few
of the leading scientists came out in support of the idea that
life originated as the result of an evolutionary process. Their
pronouncements were, however, still of a very general charac-
ter and could not overcome the stagnation in the scientific
fields concerned with the problem of the origin of life.
Scientists have acquired a large number of facts during
the twentieth century and it is only on the basis of these that
we have now, at last, been able to draw a schematic picture
of the evolutionary development of matter and set out the
stages through ^vhich it must successively have progressed
on the way to the emergence of life. As a result of this, wide
possibilities for experimental work on the problem of the
origin of life have been opened up. This time, though,
interest was not focussed on hopeless attempts to discover
instances of spontaneous generation but on the study and
experimental reproduction of phenomena which were not
merely possibilities but were completely subject to natural
laws and took place successively in the evolutionary develop-
ment of matter.
This situation gave rise to a complete recasting of the
ideas of scientists in relation to the problem of the origin
of life. During the course of nearly all the first half of the
twentieth century this problem was almost entirely excluded
from the domain of science and it only received an insignifi-
INTRODUCTION Xlll
cant amount of space in the scientific literature of the world.
Now, however, large numbers of books, articles, reviews and
exj>erimental papers are already being devoted to it. To-day
we are not satisfied by any merely speculative interpretation
of the history of the phenomena which have occurred at some
time or another on our planet. We must check our knowledge
by experiment. We must reproduce experimentally the
separate stages in the historical development of matter and
finally create life again, synthetically, not by the long and
devious route by which this synthesis took place in nature,
but by a route based on a thorough understanding of those
forms of organisation which we find already in a finished
state in existing living things.
This task is certainly exceptionally complicated but con-
temporary science has indications upon which it can, at least,
make an estimate of the work in real terms.
In what follows I shall do my best to make clear the ways
in which human minds have tried to solve the problem of
the origin of life. I shall give a short account of the numerous
doctrines and theories which have been formed during many
centuries, but I shall devote the greater part of my attention
to drawing a picture of the progressive development of matter
which, in my opinion, led up to the emergence of life on
our planet.
CONTENTS
Preface ... ... ... ... v
Translator's Preface ... ... ... vii
Introduction ... ... ... ix
Chapter I
THEORIES OF THE SPONTANEOUS GENERATION
OF LIFE
Ancient and mediaeval beliefs .. . ... ... ... i
Redi's experiments ... ... ... ... ... 17
Hypotheses concerning the spontaneous generation of
microbes... ... ... ... ... ... 19
The work of Pasteur ... ... ... ... ... 28
Chapter II
THE THEORY OF THE ETERNITY OF LIFE
The theory of the eternity of life among the ancients ... 43
The emergence of hypotheses concerning the eternity of life
in the nineteenth century ... ... ... ... 45
The theory of cosmozoe ... ... ... ... 53
Arrhenius' theory of panspermia ... ... ... 57
The state of the problem at the present day ... ... 60
XV
737I5
XVI CONTENTS
Chapter III
ATTEMPTS AT A SCIENTIFIC APPROACH TO
THE PROBLEM OF THE ORIGIN OF LIFE
The mechanistic concept of the self-formation of living
things ... ... ... ... ... ... 73
The views of Haeckel and Pfliiger ... ... ... 77
Attempts to construct ' models of living organisms ' ... 86
The evolutionary theory of the origin of life ... ... gs>
Chapter IV
THE ORIGINAL FORMATION OF THE
SIMPLER ORGANIC SUBSTANCES
The question of the original formation of organic sub-
stances ... ... ... ... ... ... 107
The distribution of organic substances (hydrocarbons) on
different heavenly bodies ... ... ... ... 115
Geological finds of hydrocarbons formed abiogenically on
the Earth ... ... ... ... ... 125
Theory of the origin of the Earth ... ... ... 131
Ways in which organic compounds could have arisen
during the formation of the Earth ... ... 136
Chapter V
ABIOGENIC ORGANIC CHEMICAL EVOLUTION
OF CARBON COMPOUNDS
Thermodynamics and kinetics of the transformation of the
simplest hydrocarbons in the lithosphere, atmosphere
and hydrosphere of the Earth ... ... ... 153
Reducing conditions ... ... ... ... ... 158
CONTENTS Xvii
Sources of energy ... ... ... ... ... 161
The origin of carbohydrates, lipids, porphyrins, amino
acids, nucleotides, polynucleotides and protein-like
polypeptides ... ... ... ... ... 189
Chapter VI
THE STRUCTURE AND BIOLOGICAL FUNCTIONS
OF PROTEINS AND NUCLEIC ACIDS AND
THE PROBLEM OF THEIR ORIGIN
Chemical structure and biological functions of polypeptides
and proteins ... ... ... ... ... 229
The amino acid composition and sequence in the structure
of the macromolecules of proteins ... ... ... 236
Hormones, enzymes, antibiotics and antigens ... ... 243
The biosynthesis of proteins ... ... ... ... 259
Chapter VII
THE DEVELOPMENT OF ORGANIC
MULTIMOLECULAR SYSTEMS: THEIR
ORGANISATION IN SPACE AND
IN TIME
Simple and complex coacervates ... ... ... goi
The structure and properties of complex coacervate drops 307
Points of similarity between complex coacervates and
protoplasm ... ... ... ... ... si 1
Stationary open systems ... ... ... ... 321
The thermodynamics and kinetics of open systems ... 323
The initial systems from which living things arose ... 335
XVUl CONTENTS
Chapter VIII
THE ORIGIN OF THE FIRST ORGANISMS
The evolution of the initial systems ... ... ... 347
The principle of selection ... ... ... ... 349
Processes of self-renewal of the systems ... ... ... 354
The origin of the capacity of the systems for self-preserva-
tion and growth ... ... ... ... ... 356
The origin of the highly dynamic state of the systems ... 358
The origin of systems capable of reproducing themselves 359
The evolution of metabolism: the origin of enzymes ... 363
The origin of the co-ordinated networks of reactions: the
origin of the first organisms ... ... ... 374
Chapter IX
THE FURTHER EVOLUTION OF
THE FIRST ORGANISMS
The concept of comparative biochemistry
The first living things — heterotrophs and anaerobes
Different forms of energy metabolism ...
Photochemical reactions
The formation of free oxygen
Chemosynthesis
Photosynthesis
The origin of respiration
Conclusion ...
Index
397
399
419
438
448
450
455
464
487
491
CHAPTER 1
THEORIES OF THE SPONTANEOUS
GENERATION OF LIFE
Ancient and mediaeval beliefs.
For many centuries people considered that the Earth was
flat and immovable and that the Sun circled round it, rising
in the east and hiding itself behind the sea or the mountains
in the west. This false belief rested on direct uncritical
observation of surrounding natiue. Observations of this kind
often suggested that living things, for example insects,
worms, and sometimes even fish, birds and mice could not
only be born from things like themselves but could also arise
fully formed by spontaneous generation, out of mud, dung,
earth or other inanimate substances.
We may find a belief in the possibility of the spontaneous
generation of living things amongst all peoples and at all times;
beginning in remote antiquity and finishing in our own days.
Even now, in the period of the blossoming of exact science in
the culturally advanced nations, it is common for their ordin-
ary inhabitants to be convinced that maggots arise from dung
and rotting meat and that various domestic pests arise of
their own accord out of rubbish, mud and dirt. These super-
ficial observations miss the fact that dung and filth are to be
found in those places where pests lay their eggs from which
the new generation of living things develops.
Tremendous significance ^vas attached to these everyday,
uncritical observations of creation characteristic of ancient
peoples, at a time when nature was still not studied in detail,
nor submitted to analysis and dissection but was accepted
in its entirety as the immediate perception of the intuition.
In his book Urzeugung und Lebenskraft, E. O. v. Lippmann^
gives a wide range of material to show how extensively such
1 1
2 THEORIES OF SPONTANEOUS GENERATION
beliefs were held. For example, in China in remote times
people believed that aphids would grow by spontaneous
generation on bamboos if the young shoots were planted out
in warm moist weather. In the Indian holy books there are
also references to the sudden appearance of various parasites,
flies and beetles from sweat and dung. In the cuneiform
writings of Babylon one may read that the mud of canals
forms Avorms and other animals from its substance.^
In ancient Egypt the view prevailed that the layer of silt
left behind after the flooding of the Nile could give rise to
living creatures when it was warmed a little by the sun.
Frogs, toads, snakes and mice could originate in this way.
In this case one might easily convince oneself by direct
observation that the front part seemed already finished and
alive while the hind part still consisted of undifferentiated
damp earth.
We also find a repetition of these tales among the ancient
Greeks (e.g. Diogenes Apolloniates) and in the writings of
the famous Roman sage, Pliny. Such stories were widely
current both in the East and the West, in the Middle Ages
and far more recently. Shakespeare's audiences were not
surprised when Lepidus, in Antony and Cleopatra, asserted
that in Egypt crocodiles are produced from the mud of the
Nile under the influence of the warm southern sun.^
In general, it appears to be highly characteristic of the
history of spontaneous generation that among diverse peoples
living at different times and at different cultural stages, w^e
almost ahvays find stories of the spontaneous develop-
ment of organisms of one kind or another. Here maggots
arise from dung and rotting meat, here lice form themselves
from human sw^eat, here fireflies are born from the sparks
of a funeral pyre, and finally, frogs and mice originate from
dew and damp earth. Wherever man has met with the un-
expected and exuberant appearance of living things he has
regarded it as an instance of the spontaneous generation of
life. Among the ancient peoples the belief in spontaneous
generation did not arise as a consequence of any particular
philosophy. For them spontaneous generation was simply an
obvious, empirically established fact the theoretical basis of
which was of secondary importance.
ANCIENT AND MEDIAEVAL BELIEFS $
The ancient teachings of India, Babylon and Egypt bound
up the origin of Hfe with various reUgious legends and tradi-
tions. From this point of view spontaneous generation was
merely a particular manifestation of the creative will of gods
or demons. But at the very source of our European culture
in ancient Greece, on the replacement of theogony, a mystical
interpretation of nature, cosmogony arises as the beginning
of scientific investigation.
Although all the Greek philosophers from the Miletians to
Epicurus and the Stoics acknowledged spontaneous genera-
tion as an incontrovertible fact, their philosophical treatment
of this fact ^vent far beyond the framework of the previous
mystical presentations.^ They contained the beginnings of
all the concepts which were developed later in connection
with the question of the origin of life.
Even the earliest Greek philosopher, Thales, who lived
from about 624 to 547 e.g., approached the problem of the
essential nature and origin of life from an elementary-
materialist position. Thales and the other philosophers of the
Miletian school (Anaximander and Anaximenes) recognised,
as a fundamental principle, the objective existence of matter
as something which is ahvays living and always changing
from the beginning of time. Life is inherent in matter as
such. Thus, although the Miletians believed in the spon-
taneous generation of living things from mud, slime and
such materials, they treated this phenomenon as the self-
creation of individual organisms, and not as one requiring
the intervention of any special mystical force. This point
of view was developed later by Empedocles^ (c. 485-425 b.c),
who held that plants and animals are formed from substances
^vhich, although not organised, are already living, either by
birth fiom things like themselves or from things unlike them-
selves, i.e., by spontaneous generation. A particularly clear
enunciation of the idea of the self-creation of living things
is to be found in the works of Democritus^ (460-370 e.g.).
In this doctrine ancient Greek materialism reached the height
of its development although it had also already acquired a
somewhat mechanistic character. According to the view of
Democritus matter forms the basis of the universe and
consists of a multitude of very small particles (atoms) which
4 THEORIES OF SPONTANEOUS GENERATION
are in constant motion and are separated from one another
by empty spaces. This mechanical motion of the atoms is
inherent in matter, and on it depends the process of organisa-
tion of all individual objects. In particular, life appears, not
from an act of divine creation, but as the result of the
mechanical forces of nature itself. According to Democritus
the primary development of living creatures, or their spon-
taneous development from water and mud, occurs when
minute particles of moist earth come together with atoms
of fire in a fortuitous but completely determinate way in the
course of their mechanical movement. Another illustrious
ancient Greek thinker, Epicurus^ (342-271 B.C.) took up the
same philosophical position a hundred years later. We may
find an exposition of his views in the well-known poem of
Lucretius Carus, De rerum natural According to this source,
Epicurus taught that, thanks to the moist heat of the sun
and the rain, there arise from earth or manure, worms and
a multitude of other creatures. But this happens without
the participation of any spiritual influence whatever. Spirits,
in the form of non-material forces, do not exist, according
to Epicurus. The spirit is material and consists of small, very
delicate and smooth atoms. The mechanical juxtaposition of
atoms in empty space also leads to the formation of multi-
farious things, in particular, living beings. According to
him, the cause of the motion of the atoms resides in matter
itself and does not depend on any ' initial impulse ' or other
meddling of gods in the affairs of the world.
Thus, even hundreds of years before the beginning of
our era, the phenomenon of spontaneous generation was
explained materialistically by many schools of philosophers
as being the self-creation of living things without the parti-
cipation of any spiritual forces. The matter may be summed
up historically by saying that the later development of the
idea of spontaneous generation was bound up, not with the
materialistic ' line ' of Democritus but with the opposing
idealistic ' line ' of Plato.
Plato himself (427-347 b.c.) hardly concerned himself directly
with the problem of spontaneous generation. In the Phaedo
he only touches superficially on the question of the possibil-
ity of the formation of living things under the influence of
ANCIENT AND MEDIAEVAL BELIEFS 5
warmth and decay. However, in complete harmony with his
general philosophical position, he maintained that life is not
inherent in plant and animal matter but this can only be
brought to life by the infusion into it of the immortal spirit
or Psyched
This idea of Plato's played a tremendous part in the later
development of the problem in which we are interested. It
was reflected to some extent in the teaching of Aristotle
which later formed the basis of the mediaeval scientific
culture and dominated people's minds for nearly 2000 years.
Aristotle (384-322 b.c.) gave to mankind by far the broadest
synthesis of the achievements of ancient science, embracing
all the factual material ^vhich had been accumulated up till
that time. He unfolded his views on the origin of life in
a number of biological works concerning the origin of
animals: Historia animalium, De partihus animaliiun , and
De generatione animalium}'^ According to Aristotle animals
are born from others like themselves but equally, they arise
and always have arisen by spontaneous generation from non-
living matter. He wrote as follows :
Such are the facts, everything comes into being, not only from
the mating of animals but from the decay of earth and dung. . . .
And among plants the matter proceeds in the same way, some
develop from seed, others, as it were, by spontaneous generation
by natural forces ; they arise from decaying earth or from certain
parts of plants.
Ordinary worms, the grubs of bees and wasps and also
ticks, greenflies and various other sorts of insects arise,
according to Aristotle, from dews in the presence of decaying
mud and dimg, from dry trees, hair, sweat and meat. All
sorts of intestinal worms are formed from decomposing parts
of the body and excreta. Midges, flies, moths, mayflies, dung
beetles, cantharides, fleas, bugs and lice (partly as such and
partly as grubs) arise from the slime of wells, rivers and seas,
from the soil of the fields, from mould and dung, from rot-
ting wood and fruit, the dirt of animals, from all sorts of
filth, from the sediment of vinegar and also from old wool."
Not only insects and worms but other living things can,
according to Aristotle, arise by spontaneous generation. Thus
6 THEORIES OF SPONTANEOUS GENERATION
crayfish and various molluscs originate from wet earth and
decaying slime, eels and some other fishes from marine silt,
sand and decaying water weeds. Even frogs, and under
certain circumstances salamanders too, can arise from the
ciu'dling of slime. Mice arise from damp earth. Some higher
animals also arise in a similar way, first manifesting them-
selves in the form of worms. " For this reason, and concern-
ing human beings and quadrupeds ", Aristotle wrote, " if
they were sometimes earth-born, as some people maintain,
one may postulate two methods of arising, either from worms
which form themselves first, or from eggs."
However Aristotle did not merely describe various cases
of spontaneous generation. An important feature of his work
was that he gave a theoretical analysis of this phenomenon
and founded his theory of spontaneous generation. In the
course of time it seems that his views changed, but in the
last analysis they served as the basis of the idealistic
hypotheses concerning the origin of life.
Aristotle considered that living things, like all other
concrete objects (substances), are formed by the conjunction
of some passive principle, ' matter ' (by this word Aristotle
obviously meant what we now call material), with the active
principle of ' form '. The ' form ' of living things manifests
itself in the ' entelechy of the body ' — the soul. This shapes
the body and sets it in motion. Thus matter does not possess
life but is infused with it. It is adapted and organised by
means of a spiritual force ; an orientating internal substance
(entelechy) brings matter to life and sustains the living
thing. The spirit, however, is already inherent in the actual
elements from which living things are formed, it is inherent
in a smaller degree in the earth and in a greater degree in
water, air and fire. Because of this, that which is created by
the spirit depends substantially on the preponderance of this
or that element. Earth produces mainly plants ; water,
aquatic animals ; air, the inhabitants of the land ; and fire,
the supposed inhabitants of the celestial bodies, in particular,
the moon. For their ' form ' living things which arise from
others like themselves depend on ' animal warmth ' and
when they arise by spontaneous generation on ' solar
ANCIENT AND MEDIAEVAL BELIEFS 7
warmth '. Thus, in spontaneous generation, decaying
materials do not on their own give rise to Hfe ; they are
brought to life under the influence of the light of the sun
which gives ' psychic warmth '.
The views of Aristotle exerted an enormous influence on
the whole subsequent history of the problem of the origin
of life. Aristotle, with his undisputed authority, supported
the results of direct, naive observation, and for many
centuries ahead prejudiced further study of spontaneous
generation. All the later philosophical schools, both Greek
and Roman, completely shared the opinion of Aristotle on
the possibility of spontaneous generation of living beings.
Moreover, as time went on the theoretical basis of the
' phenomenon ' took on a more and more idealistic, indeed
even mystical, character.
A whole series of writings, from the 3rd and 2nd centuries
B.C., contain numerous tales and ' miraculous stories ' of
* plagues of lice ' in which the juices of the human body are
changed into parasites, of the appearance of worms and
insects from rotting materials, of crocodiles from the mud of
the Nile, and so forth. Concerning such matters, the most
authoritative philosophical school of that time, the Stoics,
taught that animals and plants originate as a result of the
activity of ' engendering force ' which is a property of
pneiima.
From the later Stoics this view obtained a wide circula-
tion in both East and West, through a number of
philosophers and writers, particularly the much-travelled
Poseidonius. It thus obtained general recognition at the
beginning of our own era. In scientific treatises, in political
pronouncements and in artistic productions of that period
we meet continually with descriptions of various cases of
spontaneous generation. We find them in the works of
Cicero, of the famous geographer Strabo, of the versatile
scholar Philo of Alexandria, of the historian Diodorus
Siculus, of such poets as Virgil and Ovid, as well as in the
works of the later WTiters Seneca, Pliny, Plutarch and
Apuleius.^^
The idealistic character of the teachings concerning spon-
taneous generation was clearly expounded by the neo-
8 THEORIES OF SPONTANEOUS GENERATION
Platonists (in the third century a.d.). The leader of this
philosophical school, Plotinus, taught that living things could
originate from earth, and that this method of origin was not
confined to the past but also continues now, in the course of
decay. He explained this phenomenon as the result of the
animation of matter by a life-giving {vivere facit) spirit, and
it seems that he was the first to formulate the concept of
the ' Life Force ' which has persisted even up to the present
in the teachings of the contemporary vitalists/^
Early Christianity borrowed guiding ideas concerning spon-
taneous generation from the Bible, which in its turn borrowed
its material from the mystical tales of Egypt and Babylon.
The theological authorities of the end of the fourth and
beginning of the fifth centuries a.d., ' the fathers of the
Christian Church ', combined these legends with the teachings
of the neo-PIatonists and elaborated their mystical conception
of the origin of life on this basis.
Living in the middle of the fourth century a.d. was St.
Basil the Great who was then and still is one of the leading
religious authorities of the Eastern Church. It was under
his influence that the leaders of the Orthodoxy formulated
their beliefs concerning the origin of life. His book
Hexaemeron still retains its place in Church literature,
particularly in the Russian language. Discussing the problem
in which we are interested, he writes as follows :
For if there are creatures which are successively produced by
their predecessors, there are others that, even today, we see born
from the earth itself. In wet weather she brings forth grass-
hoppers and an immense number of insects which fly in the air
and have no names because they are so small ; she also produces
mice and frogs. In the environs of Thebes in Egypt, after abun-
dant rain in hot weather, the country is covered with field mice.
We see mud alone produce eels ; they do not proceed from an
egg, nor in any other manner ; it is the earth alone which gives
them birth. ^■^
According to Basil the Great all these instances of the
spontaneous generation of life (many of which were obviously
borrowed from Aristotle) occurred by divine command which
has continued to act with undiminished force from the
creation of the world to the present day.
ANCIENT AND MEDIAEVAL BELIEFS Q
St. Augustine of Hippo is a high authority for the Western
Church Hke St. Basil for the Eastern. He also accepted the
spontaneous generation of living things as an unchanging
truth and strove in his teachings simply to bring the pheno-
menon into line with the world philosophy of the Christian
Church. Similarly, he wrote " God as a rule creates wine
from water and earth through the mediation of grapes and
their juice; however sometimes, as in Cana of Galilee, he can
create it directly from water. Thus also, in respect of living
things, he may cause them to be born from seeds or to
emerge from inanimate matter where invisible spiritual seeds
{occulta semina) repose."
Thus Augustine saw in the spontaneous generation of
living things a manifestation of divine will — the animation
of inert matter by the ' life-creating spirit '. In this he
affirmed a doctrine concerning spontaneous generation which
was in complete agreement with the dogmas of the Christian
Church. ^^
Throughout the Middle Ages a belief in spontaneous
generation held undivided sway over people's minds.
Mediaeval philosophical thought could exist only as theo-
logical thought, embodied in one or another doctrine of the
Church. Any kind of philosophical question could only
obtain a hearing if it was linked with one or another
theological problem. Philosophy became the ' handmaid of
theology ', ancilla theologiae}^ The problems of science were
relegated to a lower plane. People did not use observation
and experiment as a guide to an understanding of nature but
used instead the teachings of the Bible and of theological
treatises. Only a very scanty knowledge of the problems
of mathematics, astronomy and medicine penetrated into
Europe from the Arab and Hebrew teachers.
It was in this way that the works of Aristotle first reached
the European peoples, though often in the form of garbled
translations. At first his teachings appeared dangerous, but
later, when the Church appreciated the full usefulness of
these teachings for many of its purposes, it raised Aristotle
to the status of ' the forerunner of Christ in the realm of
nature ' (praecursor Christi in rebus naturalibus). Accord-
ingly, in the apposite words of V. Lenin, " the scholasts
lO THEORIES OF SPONTANEOUS GENERATION
and clerics seized upon that which was dead in Aristotle
and not upon that which was alive " }'' This teaching was
widely accepted by theologians in the Middle Ages, especially
insofar as it concerned the origin of life. They held that the
animation of lifeless matter by the ' eternal divine spirit '
constituted the essence of it.
As an example one may here quote from one of the greatest
exponents of scholastic Aristotelianism, the Dominican Albert
von Bollstadt, known as Albertus Magnus (1193-1280).
According to tradition, Albertus Magnus took a gieat interest
in zoology, botany, alchemy and mineralogy. But in his
numerous works he assigns considerably less place to indepen-
dent observations than to material borrowed by him from
ancient authors. On the question of the origin of life Albertus
Magnus consistently supported the theory of spontaneous
generation, and in his book De mineralihus he specially
emphasised the fact that the origin of living things in the
presence of decay occurs as a result of the ' animating force '
{virtus vivificativa) of the stars.
In his writing on zoology Albertus Magnus gives many
accounts of the spontaneous generation of insects, worms,
eels, mice, etc., from various sorts of decaying materials, from
moist earth, vapours, sweat and various forms of filth. In
just the same way vapours of the earth and water give rise,
under the influence of warmth and the light of the stars, to
numerous plants, not only fungi but even to herbs, bushes
and trees which often grow in places where their seed cannot
have been carried.^*
The pupil of Albertus Magnus, Thomas Aquinas (1225-
1274)^® also held such opinions. In his chief work, Summa
Theologica, he deals with questions concerning the origin
of life. In doing so he relies partly on the views which he
ascribed to Aristotle and partly on the teachings of Augustine
about the ' anima vegetativa '. He thus freely accepted the
possibility of the spontaneous generation of such animals as,
for example, worms, frogs and snakes as an effect of the
warmth of the sun in the presence of decay. Even those
worms which torment sinners in the infernal regions arise,
according to the opinion of Thomas Aquinas, in this way
from the rotting of their sins. In general Thomas believed
ANCIENT AND MEDIAEVAL BELIEFS 11
in and preached a militant demonology. He taught that the
Devil really exists as the chief of a whole horde of demons.
Hence he conceived the idea that various forms of pest harm-
ful to man can arise as the result of tricks of the Devil and
the spirits of evil subservient to him.
The practical results of this hypothesis manifested them-
selves in the numerous trials of witches who were charged
with letting loose mice and other pests on to the fields and
thus destroying the sown seed. And it is well known that
Catholic bishops also used all sorts of spells and exorcisms
in an effort to cast out worms, mice, cockchafers and other
harmful creatures from the fields of those who had been
confided to their care. According to Uhland, the Swiss and
Tyrolese bishops in the sixteenth century laid the curses of
the Church on all sorts of agricultural pests and, according
to Bodenheimer, ceremonies of this sort persisted until the
end of the eighteenth century.^"
We have dwelt at some length on the views of Thomas
Aquinas because, to this day, his teaching is acknowledged
by the Catholic Church as the only true philosophy. Thus,
the Western Church has retained through all the centuries
the principle of the spontaneous generation of living things
according to which living things originate from inanimate
matter as a result of animation by a spiritual principle.
The standpoint of the theological authorities of the Eastern
Churches is similar. In this matter they rely chiefly on the
pronouncements of Basil the Great. The opinions on this
subject of the outstanding and active participants in the work
of the Russian Church, Dimitrii Rostovskii and Theofan
Prokopovich, though formulated as late as the eighteenth
century, may serve as an illustration. Dimitrii, bishop of
Rostov, lived in the time of Peter I and in his works Ajinals
relating shortly the acts from the beginning of the world
until the birth of Christ (1708) he wrote that Noah did
not take in his ark those animals which are capable of spon-
taneous generation ; they were destroyed on the ground by
the flood and then arose anew.
Moreover, from the moisture of the earth, from decay and
putrefaction, there arise mice, toads, scorpions and other
12 THEORIES OF SPONTANEOUS GENERATION
creatures which creep upon the earth, and various Avorms and
even beetles, cockchafers and cockroaches ; and also from
heavenly dew there are conceived midges and gnats and other
such things. These all perished in the Flood and after the flood
they arose anew from such beginnings. ^^
In the course of theology which he gave in the Ecclesiastical
Academy in Kiev Theofan Prokopovich developed, almost
word for word, the same idea.
Furthermore, there is a multitude of animals which arise
without copulation of the parents ; independently, from rotten
things, and there was thus no necessity to give shelter in the ark
to creatures such as mice, worms, wasps, bees, flies and scor-
pions.^^
Even in the nineteenth century a translation of a book by
W. Frantze* was published by Benjamin, archbishop of
Nizhegorod, in which it was stated that insects, worms, frogs
and mice arise by spontaneous generation " from rotting tree
stumps, from the dung of animals, from the sand of the sea,
from decaying earth, from corpses . . . etc."^^
As we have already pointed out, science was at a very low
ebb in mediaeval Europe. It was in complete subjection to
theology. The natural phenomena observed by the travellers
and learned men of those times were not only discussed, but
also described, as though scholastic wisdom demanded that
they should be in complete conformity with the Church
dogmas. The works of the learned men of the Middle Ages
therefore abound in those same fantastic descriptions and
sometimes even sketches of the spontaneous generation of
various insects, worms and fishes from slime and damp earth,
of frogs from the dews of May, and even of lions from the
stones of the desert. It is specially characteristic of the medi-
aeval methods of the study of nature that at this time there
was a wide diffusion of lore concerning goose trees, vegetable
lambs and homunculi.
According to the testimony of very authoritative men of
learning of those times, geese and ducks arise from barnacles
which in their turn are derived from the fruits of trees. From
these latter, birds may also be formed directly.
*Historia animalium sacra etc. Editio sexta. Wittebergae, 1659. — Translator.
ANCIENT AND MEDIAEVAL BELIEFS 13
We find this tale of the goose tree as early as the beginning
of the eleventh century in the works of Cardinal Peter
Damian (1007-1072). The English encyclopaedist Alexander
Neckam (1157-1217) considered that birds are formed from
the resin of conifers on contact with the salt water of the sea.
Furthermore, this story of the vegetable origin of ducks and
geese became so widely accepted that their meat was used as
lenten fare though this was later forbidden by a special order
of Pope Innocent III (1 198-1216).
But in spite of this, almost three centuries later, at the end
of the fifteenth century, the nobleman Leo von Rozmital
described a dinner gi\en in his honour in London by the
Duke of Clarence at which, as a hot dish described as fish
(for lenten fare), were served ducks, which there generate
themselves from ' worms ' in the sea. However, Rozmital
remarks that the taste of these ' fish ' was exactly like that
of ducks. ^*
It is interesting that the story of the goose tree persisted
until the end of the sixteenth and even the beginning of
the seventeenth century. A series of authors describe their
personal observations on this subject and even give more or
less fantastic drawings showing how the birds are gradually
formed from the fruits of the tree.
Evidently this legend was based on the naive interpretation
of superficial observations of barnacles of a special kind.
In the adult state these marine animals attach themselves
by a special kind of stalk to rocks, stones, the bottoms of
ships and trees which have accidentally fallen into the water.
On the shores of the north of Scotland, Ireland and the
neighbouring islands this happens at the time when flocks
of young Arctic geese fly there from the north.
These two phenomena were confused and fantasy, not
knowing where they came from, drew a picture of the forma-
tion of birds from the barnacles found on the branches of
trees. It may also be that analogous superficial observations
formed the basis for the other stories concerning vegetable
lambs. The well-known traveller Odoric di Pordenone (d.
1331) was the first to record this. It was related to him by
' reliable ' people that in the Tatar kingdom of Khadli there
grew enormous gourds which opened when they were ripe
14 THEORIES OF SPONTANEOUS GENERATION
to reveal within themselves lambs covered with white wool
and having very delicious meat. ' Sir John Mandeville '
described his travels in Eastern lands and also told stories of
a whole tree, from the melon-shaped fruits of which there
arose living sheep. -^ This story persisted for centuries and
as late as the middle of the seventeenth century it was
repeated anew by Adam Olearius in his descriptions of his
travels in Muscovy and Persia. He wrote :
We were told that there beyond Samara, between the rivers
Volga and Don, there grows a rare form of melon or rather
pumpkin which is very like an ordinary melon in size and shape
but its appearance reminds one of a lamb because it has clearly
defined limbs. The Russians therefore call it the 'little ram'. This
' vegetable lamb ' feeds on the grass around it but frequently
falls a prey to wolves, which are very fond of it.
Later, Olearius writes that he had the good fortune actually
to see the wool of such a sheep. ""^
The story of the homunculus developed on the basis of
alchemical experiments. It is known to have made its appear-
ance as early as the first century a.d. This story was based on
the supposition that by mixing the passive maternal original
substance with the active masculine one it is possible to re-
produce artificially the phenomenon of birth and to obtain
the embryo of a tiny person — homunculus.
Like the legend of the goose tree and the vegetable lamb,
stories about the homunculus were current throughotit the
Middle Ages and are to be met with in many alchemical
treatises. A typical exponent of the earlier natural philosophy
of the sixteenth century, Theophrastus Bombast von Hohen-
heim, known as Paracelsus (1498-1541), even gives an 'exact
receipt ' for the preparation of homunculi. For this it is
necessary to obtain human sperm, place it in a sealed gourd
inside a horse's stomach and during the course of a certain
time to carry out a series of complicated manipulations. In
this way there is formed a small person complete in all its
parts, like children born of women but on a far smaller scale.
In general, Paracelsus was a convinced supporter of the
spontaneous generation of living things. He maintained that
there is an active life force, the arche, which governs the
ANCIENT AND MEDIAEVAL BELIEFS I5
bodies of animals and men and which can be controlled by
means of magic remedies. This force itself determines the
formation of the organism and its later conduct. Paracelsus
developed a theory of spontaneous generation of life with
this philosophical outlook. He even produced a number of
personal observations of the sudden formation of mice, frogs,
eels and tortoises horn water, air, straw, rotten wood and all
sorts of rubbish." The descriptions of the views and beliefs
of the learned men of the Middle Ages were excellently
portrayed in Goethe's tragedy Faust. Here Mephistopheles
refers to himself as " Der Herr der Ratten und der Mduse,
der Fliegen, Frosche, Wanzen, Lduse " , and a swarm of insects
fly out fiom his old doctor's fur cloak and praise him not
only as their patron but also as their father, as though he had
actually begotten them there and then.
The part played by the homunculus in the second part of
Faust is also well known. Wagner takes great pains with the
preparation of his alchemical experiments. For this he mixes
hundreds of substances, corks them up in a retort and
proceeds to purify them by distillation. If the conjunction
of the stars were favomable a manikin should develop in the
retort. But even in this case the spontaneous generation did
not occur without the intervention of Mephistopheles, whom
the homunculus greeted as his ' cousin ' }^
In the second half of the sixteenth century and, in par-
ticular, in the seventeenth century, observations of natural
phenomena were getting more accurate. Copernicus (1473-
1543), Bruno (1548-1600) and Galileo (1564-1642) destroyed
the old Ptolemaic system and drew up sound theories concern-
ing the universe of stars and planets which surround us.^^
However, this blossoming of exact knowledge did not as yet
touch upon biological problems. The idea of the primary
spontaneous generation of living things remained unchal-
lenged in the minds of the investigators of that time.
As an example we may here mention the well-known
physician of Brussels, van Helmont (1577-1644). He used
some methods of exact experiment which enabled him to
make substantial progress in the study of the complicated
problem of the nutrition of plants. Nevertheless, he was
quite convinced that living things could arise by spontaneous
l6 THEORIES OF SPONTANEOUS GENERATION
generation and even went further and carried out a number
of observations and experiments to confirm the hypothesis.
For example, he gives a well-known receipt for making mice
from gi'ains of wheat. He held that human sweat could serve
as the life-giving principle. For this it was necessary to place
a dirty chemise in some sort of receptacle which contained
wheat grains. After 21 days the ' fermentation ' was stopped
and the exhalations from the shirt together with those of
the corn had formed living mice. It was especially surprising
to van Helmont that these artificially produced mice were
exactly like those born from the seed of their parents.^"
Neither did Harvey (1578-1657), the originator of the
theory of the circulation of the blood, reject the idea of spon-
taneous generation. However, although the celebrated phrase
omne vivum ex ovo (everything alive comes from an egg)
belongs to him, he was here giving a very wide meaning to
the word egg. He considered generatio aequivoca (spontane-
ous generation) of worms, insects, etc., to be perfectly possible
as a result of the activity of special forces which develop
during putrefaction and similar processes. ^^
This also was the view of Harvey's contemporary, the
founder of seventeenth century English materialism, Francis
Bacon (1561-1626). In his works he expressed the opinion
that various plants and animals (such as flies, ants and frogs)
could arise spontaneously in the course of the decay of various
materials. However, he approached this phenomenon from
a materialist position and saw in it only a proof of the absence
of an impassable barrier between the inorganic and the
organic world. ^^
The materialistic interpretation of spontaneous generation
was particularly clearly expressed by Descartes (1596-1650).^^
This great French philosopher, although he believed the
spontaneous development of living things to be beyond
dispute, nevertheless categorically denied that this emergence
occurred under the influence of the anima vegetativa of the
scholasts, the arche of Paracelsus, the * spirit of life ' of van
Helmont or any other spiritual principle. In sharp contra-
distinction to the religious teachings then prevailing and to
the anthropocentric tendencies of mediaeval natural philos-
REDl'S EXPERIMENTS 17
ophy, Descartes tried to relate the qualitative diversity of
natural phenomena to matter and its movement.
Thus, according to Descartes, the living organism does not
need to be explained by any special obedience to ' a vital
force '. Descartes postulates nothing other than a machine,
very complicated certainly, but of completely intelligible
construction, whose movements depend exclusively on the
pressures and interactions of particles of matter as do the
movements of the wheels in a clock. Thus different kinds of
living beings can arise spontaneously from the surrounding
lifeless matter. In particular, when moist earth is exposed
to the rays of the sun or when putrefaction occurs, there
develop all kinds of plants and animals such as worms, flies
and a variety of insects. But for this to happen there is no
need for any intervention whatsoever by any ' spiritual prin-
ciple '. Spontaneous generation consists only of the natural
process of self-formation of complicated machines, a process
which takes place invariably when certain circumstances, not
yet fully investigated by us, are fulfilled.
Thus, do^vn to the middle of the seventeenth century, the
actual possibility of spontaneous generation had not been
seriously questioned by anyone. The dispute between the
mystical doctrines irom the Middle Ages and the materialism
noAV in violent spate was only concerned with the theoretical
treatment of the phenomenon: was spontaneous generation
to be regarded as a manifestation of ' a spiritual principle '
or as a natural process of self-formation of living beings?
However, the study of living nature was all the time becom-
ing both wider and more accurate in its approach, and the
assurance of those who had accepted spontaneous generation
as a ' fact ' now began to be shaken.
Redi's experiments.
In this matter the experiments of the Tuscan physician
Francesco Redi (1626-1697) can justly be counted as the
turning point. To Redi fell the honour of being the first
to emerge with the support of experiment from the
belief in spontaneous generation which had ruled without
interruption for so many centuries. In his treatise Esperienze
intorno alia genemzione degV insetti (1668) he describes
2
l8 THEORIES OF SPONTANEOUS GENERATION
a series of his experiments which show that the white
maggots in meat are simply the larvae of flies. He kept meat
or fish in a large vessel, covered with the finest Neapolitan
muslin, and, for still more complete protection, covered the
vessel with a frame on which muslin was stretched. Al-
though plenty of flies alighted on the muslin, no maggots
appeared in the meat. Redi pointed out that he had suc-
ceeded in observing how the flies laid their eggs on the
muslin, but that only when these eggs fell on to the meat did
they develop into meat maggots. From this he concluded
that decaying substances are only a place or a nest for the
development of insects, but that the laying of eggs is an
essential preliminary to their development ; without eggs
the maggots never appear.^*
It should not be thought, however, that Redi had suc-
ceeded in completely ridding himself of the notion of
spontaneous generation. In spite of his brilliant experiments,
which he had interpreted correctly, this learned man freely
admitted the possibility that spontaneous generation might
occur in other cases. Thus he states that worms in the intes-
tines or in timber arise on their own from rotting materials.
Moreover, in his opinion, the maggots which are found in
oak galls are formed from the juices of the plant. Only later
was this opinion refuted by the investigations of the scientific
physician Vallisneri (1661-1730).
This example makes it clear that what has been repeated
for centuries (though often wrongly) is not easily confuted.
Throughout the eighteenth century, and even in the
beginning of the nineteenth century, many scientists and
philosophers of different tendencies and schools, and even
more writers and poets, often described in their works various
fantastic instances of the spontaneous generation of beasts,
fishes, insects and worms, or made it clear that they con-
sidered that such a phenomenon was quite possible.
As observations of nature became more refined and, in
particular, knowledge of the structure of living things became
more detailed, so it was admitted, though only very giadually,
that the spontaneous generation of such complicated things
from structureless filth and decaying matter was impossible.
In this way the belief in the spontaneous generation of all
SPONTANEOUS GENERATION OF MICROBES 19
the more highly organised things ceased to be held among
scientists. But this idea as to the primary origin of living
things did not disappear. On the contrary, during the eigh-
teenth and nineteenth centuries it reached its fullest develop-
ment in connection with the simplest living things, the
micro-organisms.
Hypotheses concerning the spontaneous
generation of microbes.
Almost at the same time as Redi was carrying out his
celebrated experiments, a new world of living creatures
invisible to the naked eye was opened up by the Dutch
scientist Anthony van Leeuw^enhoek (1632-1723), with the
help of magnifying glasses made Avith his own hands. In
letters to the Royal Society in London he described in detail
these small ' living animalcules ' discovered by him in rain
water which had stood for a long time in the air, in various
infusions, in excrement, in the tartar of teeth, etc. With his
glass van Leeuwenhoek saw representatives of almost all the
classes of micro-organism known to us at the present day.
He gave descriptions, ^\"hich were surprisingly accurate for
those times, of infusoria, yeasts, bacteria, etc.^°
The curious discoveries of the Dutch scientist attracted the
most general attention and provoked many similar studies.
Micro-organisms -^vere discovered wherever decay or fermenta-
tion of organic substances was going on. They were foimd
in different sorts of plant infusions and decoctions, in decay-
ing meat, in stale broth, in sour milk, in fermenting wort
etc. Substances which quickly become tainted or which
decay easily had only to be kept in a warm place for some
time when microscopic living things, which had not been
there before, at once began to develop in them. As the belief
in the spontaneous generation of living things was current
at the time, it was unhesitatingly assumed that it extended
to cover the spontaneous generation of living microbes from
inanimate matter in these decoctions and infusions.
Van Leeuwenhoek himself did not propose this idea. He
maintained that the micro-organisms fell into his infusions
from the air. This opinion was confirmed by the experiments
20 THEORIES OF SPONTANEOUS GENERATION
of Louis Joblot.^^ This distinguished follower of van Leeu-
wenhoek used infusions of hay which were swarming wdth
micro-organisms, boiled them for 15 minutes and then poured
equal parts into two vessels. One of these he covered closely
w4th parchment before it cooled, the other was allow^ed to
stand uncovered. In the open vessel very small living things
(apparently infusoria) grew abundantly, but they did not
appear in the closed one. At the end of the experiment the
parchment was removed from the closed vessel too, after
w^hich the infusion was soon populated with micro-organisms.
However, the experiments of Joblot were not convincing
enough for his contemporaries and were later completely
forgotten.
Philosophical thought at that time could still not renounce
the principle of spontaneous generation and, as before, the
dispute betw^een the different schools was concerned not
with whether or not microbes can develop of their own
accord, but only with the spiritual or material basis of this
apparently self-evident ' phenomenon '.'"'
The discovery of the extremely small germs of life which
were to be found everywhere was expressed in the philo-
sophical system of G. Leibnitz (1646-1716). His teachings
about monads included metaphysical rehashing of the con-
temporary data of mathematics and science. According to
Leibnitz the monads are primary centres of spiritual force.
As the ultimate sources of everything they must be character-
ised by absolute simplicity and individuality. Matter being
inherently passive, the monads constitute the spiritual sub-
stance, for only the spirit, in Leibnitz's view, has the capacity
for uninterrupted activity.^*
Starting from these assumptions, Leibnitz considered that
life cannot be explained simply on the basis of bodily forces.
In particular, he considered the possibility that higher plants
and animals could arise by spontaneous generation from
decaying material as disproved by direct experiment. The
development and disappearance of living things is but the
evolution and involution of eternally existing germs. Those
substances which we usually consider inorganic contain
within themselves a whole world of germs of life. " Even in
vinegar and bookbinder's paste," wrote Leibnitz, " these
SPONTANEOUS GENERATION OF MICROBES 21
germs are present." Thus, all bodies can contain within them-
selves organic structures, but these are still invisible, in-
complete, and only in the form of germs. In these germs
there are already present and pre-existing all the conditions
for future specific organisation. Thus, living things are
formed spontaneously from them by later development.
We find the same ideas concerning spontaneous generation
in the works of the French scientist G. L. Buffon (1707-
1788).^* He also considered that the whole of nature is full
of ' ubiquitous units or germs of life ' but, in opposition to
Leibnitz, he attributed to them a material character. These
material particles endowed with life are capable, according
to Buffon, of uniting with one another to form lower plants
and animals from which the highly organised creatures later
e\olve. Conversely, on the decay of the body, individual
existence ceases but living particles of matter which were at
first scattered and then entered into its composition can now,
once more, unite into living bodies. From them microbes
originate. In this Buffon saw the explanation of the pheno-
menon of the spontaneous generation of microscopic organ-
isms in putrefying organic liquids and infusions.
This view was shared by the contemporary and friend of
Buffon, the Welsh Roman Catholic priest and naturalist J. T.
Needham (17 13-1 781). He believed that in each microscopic
particle of organic matter there was concealed a special ' vital
force ' which could animate the organic matter in an infusion.
Thus Needham developed vitalistic views, which were very
common in those days, concerning the essence of life and its
begetting. However, Needham's importance in connection
with the problem ^vhich Ave are considering depends, not
only on his vie^vs, but also on the extensive experiments
which he carried out in an effort to confirm the spontaneous
generation of micro-organisms. He says :
I took a quantity of mutton gravy hot from the fire and
shut it up in a phial closed with a cork so well masticated that
my precautions amounted to as much as if I had sealed my
phial hermetically. I thus excluded the exterior air that it might
not be said my moving bodies drew their origin from insects
or eggs floating in the atmosphere. I neglected no precaution
even so far as to heat violendy in hot ashes the body of the phial
22 THEORIES OF SPONTANEOUS GENERATION
that if anything existed even in that little portion of air which
filled up the neck it might be destroyed and lose its productive
faculty.
But, in spite of all this, after some days the vessel swarmed
with micro-organisms. He made similar investigations on a
variety of organic liquors and infusions, always with the same
result. This naturally led him to the conclusion that it was
completely possible, and indeed inevitable, for micro-organ-
isms to arise spontaneously from putrefying organic sub-
stances.^"
However, these experiments of Needham were subjected
to severe criticism by an Italian scientist, the priest
Spallanzani (1765). Spallanzani, like Needham, carried out
experiments with the object of establishing or refuting the
possibility of spontaneous generation, but, on the basis of
these experiments, he arrived at exactly the opposite con-
clusion. He asserted that the experiments of Needham had
succeeded because of insufficient heating of the vessels
containing the liquid, resulting in their inadequate sterilisa-
tion. Spallanzani himself carried out hundreds of experi-
ments in which plant decoctions and other organic liquids
were subjected to more or less prolonged boiling, after which
the vessel containing them was sealed and thus the access of
air to the liquids was prevented. Air, according to Spallan-
zani, carried the germs of micro-organisms. Whenever the
operation was conducted with proper attention the liquids
contained in the vessel did not putrefy and living creatures
did not appear in them.*^
Needham objected to this that on prolonged heating of
the liquids the air contained in the vessels was spoilt and
that this was the chief reason for the failure of micro-
organisms to develop. Secondly, he asserted that on prolonged
heating the ' vital force ' of the organic infusions was
destroyed. This ' vital force ' usually seems to be capricious
and inconstant and cannot withstand prolonged and severe
treatments. Thus Needham considered, not that he had
heated the liquids too weakly but, on the contrary, that in
the experiments of Spallanzani these liquors had been heated
SPONTANEOUS GENERATION OF MICROBES 2^
too Strongly and the generative power of the infusions had
thus been destroyed.
In order to refute this Spallanzani carried out fresh experi-
ments. In a long series of tests conducted with exceptional
care he answered nearly all the criticisms that had been made
by Needham.^^ Nevertheless, he did not succeed in convincing
his contemporaries and the controversy remained unsettled
for very nearly a hundred years longer.
It is interesting to note that, in parallel with Spallanzani,
in the period between the publication of his first and second
works, analogous experiments were being carried out by the
Russian M. Terekhovskii, who was sent from St. Petersburg
to Strasbourg for scientific investigations.
In his dissertation, De chao infusorio Linnaei,^^ which he
published in 1775 in Latin, Terekhovskii recorded the results
of his extensive investigations on the ' animalcules of liquors ',
i.e. the microscopic living creatures which appear in all kinds
of organic infusions — the infusoria, flagellates and other
primitive organisms. In his opinion it was absurd to
suppose that even the very simplest organisms with all the
extraordinary complication of their structures which " no
mechanic, even the most skilful who ever lived, could under-
stand completely, try as he might, still less reproduce " might
" be formed by chance from a chaotic mixture of inanimate
particles ". In effect, as S. Sobol' pointed out, the numerous
and very carefully performed experiments of Terekhovskii
showed that " the spontaneous generation of animalcules does
not take place under any conditions". However, these state-
ments and experiments of the Russian scientist, which we
now know were completely correct, did not receive recogni-
tion in the scientific world of that time and were quickly
forgotten.
The doctrine of spontaneous generation was still defended
by many scientists and philosophers in the end of the eigh-
teenth century and beginning of the nineteenth century. In
particular, it was developed by representatives of the Ger-
man idealistic philosophy. I. Kant (1724-1804)" himself con-
sidered that the primary internal cause of the development
of organisms was supernatural (metaphysical) and that there-
fore the hypothesis of spontaneous generation was merely a
24 THEORIES OF SPONTANEOUS GENERATION
' bold adventure of the intellect '. However, the later Natur-
philosophen, G. Hegel (1770-1831), F. Schelling (1775-1854)
and L. Oken (1779-1851) extensively developed the idea of
generatio aequivoca. Thus, for example, Hegel stated that
the earth and the sea had a clear need to be vivified
" but in its general form, vivification seems to be generatio
aequivoca "', and further, in his Enzyklopddie he wrote that
" the earth and, in particular, the sea generate all sorts
of lichens, infusoria, innumerable phosphorescent living
specks ".*^
According to Schelling,** there is a complete identity
between the earth and the animal and plant world. The earth
itself is transformed into plants and animals because that
w^hich is called dead matter is merely the ' dormant animal
and plant world '.
Oken,*^ who w^as a follower of Schelling, developed the
idea that the earth, in the course of its metamorphosis,
degenerates into carbon and that this, being mixed with water
and air, is converted into ' hydrated oxidised carbon ' which,
as a formless primaeval slime, acts as the basis of all organisms
which have a form. Every living thing arises from this slime.
At first, like the primaeval planets, it turns into spherical
globules (the globules of primaeval slime) or infusoria under
the influence of light. These later metamorphose into plants
and animals which afterwards, on putrefaction, give rise again
to infusoria. Moreover, it is also possible that spontaneous
generation of ticks, worms and such creatures occurs by
simple direct coagulation of the primaeval slime.
Thus, we find in the works of Oken, along with a banal
conception of the spontaneous generation of life, the elements
of a specifically scientific prediction. He had already put
forward the theory of the development of life by the gradual
evolution of matter, although in a very confused form.
While these discussions on natural philosophy were taking
place in the first half of the nineteenth century, a whole series
of experiments was carried out with the aim of establishing
or refuting the possibility of the spontaneous generation of
microbes.
An exceptional amount of care and experimental skill was
expended on elucidating the significance of air in the appear-
SPONTANEOUS GENERATION OF MICROBES 25
ance of living things in liquids which had been previously
heated.
The well-known French chemist J. L. Gay-Lussac (1778-
1850) showed, by means of direct analyses, that oxygen, that
is the component of the air which sustains burning and
breathing, is absent from vessels containing liquid which had
been sealed up after boiling. This confirmed Needham's view.
To elucidate the part played by oxygen, Gay-Lussac filled
with mercury a glass tube which was closed at one end (a
eudiometer) and stood it in a vessel of mercury with the
closed end uppermost. A grape was then inserted under the
mercury into the tube and crushed with a wire which was
introduced through the mercury. The juice which ran out
of the grape occupied the upper part of the tube. It remained
transparent and apparently completely sterile for a long time.
However, after the admission of a bubble of air, the juice
quickly began to ferment and to be inhabited by micro-
organisms.**
This experiment, which was later made great use of by the
adherents of spontaneous generation, is interesting from the
point of view that in it the source of infection was, as we
kno^v no^v^ the germs of the micro-organisms which were
present on the surface of the mercury, to which neither the
experimenter himself nor any of his later interpreters had
paid any attention.
In 1836 the German naturalist T. Schwann made a new test
of the significance of oxygen for the spontaneous generation
of microbes. He caused a stream of heated air to pass through
a glass tube into a vessel containing sterile meat broth and
showed that in these circumstances the broth did not putrefy.
Hence spontaneous generation did not proceed in the
presence of a constantly renewed stream of sterilised air.
However, a repetition of this experiment using a liquid
containing sugar gave completely different results. In spite
of the fact that, according to the author, the methods used
in them were exactly the same as those used in the experi-
ments with the broth, a mass of living micro-organisms often
developed.'*'
In the same year F. Schulze carried out analogous experi-
ments differing only in that the air which was admitted into
26 THEORIES OF SPONTANEOUS GENERATION
the vessel with the steriHsed liquid was freed from germs,
not by heating but by being passed through strong sulphuric
acid. The results were the same. However, numerous repeti-
tions of Schulze's experiments gave inconsistent results and
in some cases micro-organisms appeared in the liquids.^"
This, as we now know, depended on the invasion of the
liquid by spores which were present in a resistant state in
the bubbles of air passing through the sulphuric acid.
A little later (1853) the Heidelberg professors H. Schroder
and T. Dusch simplified the experiment still further by
purifying the air by passing it through a layer of sterilised
cotton wool which served as an excellent filter, removing all
germs of micro-organisms. Thus they were able to free the
air from germs while not submitting it to any chemical treat-
ment or applying heat to it. In fact, a series of experiments
was made by these workers with meat broths, and the wort
of beer. These were boiled and then allowed to stand for
many weeks without any change occurring. However, milk
and meat without water went bad quickly under these condi-
tions and became full of micro-organisms.^^
Although all the experiments which had been carried out
tended to refute the possibility of spontaneous generation,
their evidence was not strong enough, in that they were some-
times unsuccessful for no demonstrable reason and micro-
organisms appeared in the liquid. We now know that this
occurred as a result of the accidental introduction of organ-
isms owing to some technical fault ; however, contemporary
scientists did not see the matter in that light. All these
failures, in spite of a known wish to succeed, might easily be
interpreted, and were in fact interpreted, as indicating that
spontaneous generation, though not universal, could take
place under certain circumstances. This opinion was held
even by such outstanding investigators as Dumas, Naegeli
and a number of other scientists of the middle of the nine-
teenth century.
The conflict of opinion concerning the possibility of the
spontaneous generation of micro-organisms attained its great-
est naivete in 1859 when F. Pouchet" published a paper in
which he tried to prove this possibility experimentally. In
his voluminous work, comprising about 700 pages, Pouchet^^
SPONTANEOUS GENERATION OF MICROBES 27
developed his theory of spontaneous generation, which is
fundamentally very reminiscent of the views of Needham.
Fermentation or decay of organic substances precedes each
manifestation of spontaneous generation. Only substances
forming part of living organisms can give rise to new life.
Under the influence of fermentation or decay the organic
particles of the corpse disintegrate but, having wandered
around for some time independently, they become united
once more by virtue of their inherent properties and thus
new living things are created. Pouchet considered that a
' life force ' was a prerequisite for the development of living
things and therefore he never believed that living things
could arise de novo in mixtures of mineral substances. In
confirmation of his views Pouchet made a large series of
experiments in which he repeated the investigations of his
predecessors. In these he always got results in agreement
with his own ideas ; that is to say, micro-organisms always
developed in his organic liquids.
Only about a hundred years separate us from the
experiments of Pouchet, but when one reads about these
experiments now one cannot help noticing how crudely and
messily they were carried out. Pouchet, for example, cate-
gorically denied the possibility that germs of micro-organisms
might have got into his infusions and solutions from outside
simply because " Joly and Musset carried out careful chemi-
cal analyses of the surrounding air ". But what could they
find out in this way even if thousands of bacteria and spores
were hovering around them? In just the same way Pouchet
asserted, without any foundation, that his original hay
inftisions certainly did not contain the germs of any micro-
organisms. However, we know that enormous numbers of
such germs are always present on the surface of hay and that,
on simple infusion of the hay with water, which is what
Pouchet did, these germs must certainly fall off into the
infusion in a perfectly viable state. This clearly occurred,
for when Pouchet placed his hay infusions in a warm place
for six days there appeared in them not only bacteria, but
also such highly organised creatures as infusoria, in the cells
of which there are digestive vacuoles, mouths and other very
complicated and specialised organs. It is quite clear to us
28 THEORIES OF SPONTANEOUS GENERATION
now that under such experimental conditions the appearance
of infusoria was simply due to their germs always having
reached the original solution from the surface of the hay.
This may easily be demonstrated nowadays by direct observa-
tion. Pouchet's statement that spontaneous generation of
infusoria occurred in his infusions sounds quite unjustified
and even ridiculous in the light of present-day knowledge.
However, Pouchet's work made a great impression on his
contemporaries.
The work of Pasteur.
The French Academy of Sciences awarded a prize to who-
ever, by means of accurate and convincing experiments,
should cast light on the question of the primary origin of
living creatures. This prize was awarded to Louis Pasteur^*
who, in 1862, published his work on spontaneous generation
in which, by a series of conclusive experiments, he demons-
trated the impossibility of the formation of micro-organisms
from various infusions and solutions of organic substances.
Pasteur was successful in doing this only because he left the
beaten track of blind empiricism and approached the whole
problem broadly in his experiments. He also gave a rational
analysis of all earlier experiments and explained the mistakes
of those who carried them out. First of all Pasteur cleared
up the question of the presence of micro-organisms in the
air which, as we have seen above, was considered to be one
of their chief origins. The partisans of spontaneous genera-
tion, Pouchet in particular, repeatedly expressed doubts as to
whether germs of life were really present in air and de-
manded a demonstration of the ' infinite mass of micro-
organisms ' which are present in the air.
Pasteur solved this problem by a very simple method.
Using an aspirator he drew air through a tube into which a
plug of gun cotton had been inserted. As Schroder and
Dusch had already shown, all the smallest particles are
retained by the cotton and remain in the tube. The current
of air was maintained for 24 hours and the plug with the
dust which had been caught in it was removed and dissolved
in a mixture of alcohol and ether. At this stage all the solid
THEWORKOFPASTEUR 20
particles present sank to the bottom. They were washed with
sohent and then studied under the microscope. There were
always found thousands of organised bodies which differed
in no way from the common micro-organisms and their
spores. The presence of large numbers of organised bodies
in the ambient atmosphere had thus been demonstrated.
Furthermore, Pasteur showed that these germs which are
present in the air can often initiate the growth of organisms.
First of all he repeated the experiments of Schwann with
some variations and improvements. The boiling of the
organic liquids was carried out in a round-bottomed flask
with a long dra^vn-out neck joined to a platinum tube which
was heated to red heat with a gas burner. Thus, the air which
was drawn into the flask when the liquid in it had finished
boiling passed through a red-hot platinimi tube in which all
the germs present in it w^ere sure to be destroyed. While
passing from the tube to the flask the air was cooled by a
stream of water. After it had been filled with air the flask
was sealed and in this state it could be kept indefinitely.
When the experiment was set up in this way the liquid never
decomposed and no micro-organisms were formed. However,
if the sealed neck of the flask was broken and a cotton plug
through which air had been passed was thrown into the liquid
contained in it and the neck was quickly sealed again, then
the liqiu'd soon became filled with moulds, bacteria and even
infusoria. This meant that the liquid had not lost its nutrient
capacity for micro-organisms and the germs which had been
present in the air and were collected on the cotton plug could,
in fact, easily develop in such liquids.
Later Pasteur sterilised the air admitted to the flask
'^s'ithout heating it. For this purpose he relied partly on the
method of Schroder and Dusch. drawing the air through a
cotton-wool plug, and partly brought his own native skill
to bear on it. As usual, Pasteur half filled the round-
bottomed flask with the experimental liquid and then
softened the neck of the flask in a flame and drew it out.
The part which was drawn otit was bent into the shape of
the letter S. The contents of the flask were then boiled with-
out any further precautions. When a strong current of steam
issued from the extended neck of the flask the boiling was
30 THEORIES OF SPONTANEOUS GENERATION
Stopped and the flask was allowed to cool. Under this treat-
ment the contents of the flask remained unchanged although,
in this case, the solution was directly connected through the
curved neck with the surrounding atmosphere. This was due
to the fact that all particles of dust, including the germs of
the micro-organisms, were retained on the curved surfaces
of the S-shaped tube. If the neck was cut off the liquid was
soon colonised by micro-organisms. In this experiment the
air was submitted to absolutely no treatment and neverthe-
less decomposition of the liquid did not occur, simply because
the organisms floating in the air were denied access to it.
Further investigations by Pasteur showed that the content
of viable micro-organisms in the air was far from constant
and changed according to conditions such as season and place.
The largest number of germs is present in the air of towns
and inhabited places. The air of fields and forests is less rich
in micro-organisms, and finally in the mountains, especially
at great heights, the number of these minute living creatures
floating in the air is quite insignificant. One may therefore
open flasks containing sterile liquids without their necessarily
being exposed to infection. In many cases such flasks
remained sterile after resealing, although untreated mountain
air had been admitted to them.
Pasteur also demonstrated that the air is far from being
the only source of infection of organic liquids. The germs
of micro-organisms are present on the surfaces of all the
objects which we use in the course of an experiment. There-
fore all these objects must be meticulously disinfected.
Pasteur showed that the appearance of micro-organisms in
the experiments of earlier investigators was always due to the
fact that they had not carefully eliminated all sources of
infection. Thus, for example, Pasteur showed by direct
experiments that the source of infection of Gay-Lussac's grape
juice was micro-organisms present on the surface of the
mercury. In other cases the organisms were derived from
incompletely sterilised utensils. If all sources of error are
avoided then, as Pasteur demonstrated brilliantly in numer-
ous experiments, infection will be absent in a hundred per
cent of cases. Pasteur also succeeded in showing that it is
possible to keep even such easily decomposed liquids as urine
THE WORK OF PASTEUR 3I
and blood for an indefinite time without submitting them
to heat or any other treatment. It is only necessary to with-
draw them from the body of the animal, ^vhere they do not
contain bacteria, ^vhile taking precautions against contamina-
tion with germs from outside. Under these circumstances
such liquids do not putrefy and may be conserved in-
definitely.
Pasteur did not merely aim at getting accurate and uniform
results but also at explaining the contradictory data of other
authors. He rejected the suggestion that decaying infusions
give rise to microbes and showed that, on the contrary, the
decay of these liquids itself takes place as a result of the
vital activities of micro-organisms which have entered from
outside. All attempts to refute this hypothesis and to find a
case of spontaneous generation of any particular organism
were in vain. From our present point of view this is quite
understandable, in that micro-organisms are not simple lumps
of organic material as was believed until the time of Pasteur.
A detailed study of these very simple living things has shown
that they have a very delicate and complicated organisation.
It is quite impossible to suppose that complicated structures
of this sort could emerge in the course of a short time before
our eyes out of structureless solutions of organic substances.
This hypothesis is, in essence, just as absurd as the hypothesis
that frogs arise from the dews of May or lions from the stones
of the desert.
Pasteur's investigations quite understandably attracted tre-
mendous attention among his contemporaries. The complete
revolution in biology brought about by Pasteur may be com-
pared with that achieved by Copernicus in astronomy. For,
in the one case as in the other, prejudices which had held
sway over the minds of men for thousands of years were swept
away.
As we have seen above, many generations of scientists and
philosophers considered the possibility of spontaneous genera-
tion to be an incontrovertible and self-evident truth. The
obdurate struggles bet^veen idealism and materialism were
only concerned ^\'ith the theoretical explanation of the
* phenomenon '. And now it was suddenly discovered that
the ' phenomenon ' itself, the very ' fact ' of spontaneous
32 THEORIES OF SPONTANEOUS GENERATION
generation, was illusory and was based on false interpreta-
tions of observations and incorrect conduct of experiments.
At the end of the last century and the beginning of the
present one the two warring philosophical camps redeployed
their forces in the light of this discovery.
Vitalism, the idealistic tendency in biology, had already
achieved its most exuberant development by the middle of
the eighteenth century. At that time our knowledge of life
was so limited that it seemed quite impossible to explain
physiological and formative processes without recourse to the
activity of some special, mysterious ' life force '. However,
at the end of the eighteenth century there was a tremendous
surge of great discoveries in physics and chemistry, and from
that time onwards vitalism suffered one defeat after another.
Even by the second quarter of the nineteenth century it had
really almost played itself out. The evolutionary theory of
Darwin dealt a final crushing blow to vitalism. It showed
the way to a scientific, materialistic solution of the problem
of the adaptation of form to purpose in the organic world.
After this the concept of a ' life force ' became quite un-
necessary, it explained nothing and was a purely mystical
and meaningless word.
However, the end of last century witnessed a resurgence
of vitalism, which now chose the problem of the origin of
life as one of its main rallying points. In 1894 I. Borodin"
wrote " Has not the progress of science in the course of cen-
turies furnished the vitalists to some extent with weapons?
Yes, they certainly have such weapons, they hold a trump
card in their hand." Borodin meant by this ' trump ' the
unsuccessful attempts to discover the phenomenon of spon-
taneous generation. These failures, in his opinion, indicated
the presence of an impenetrable barrier between the animate
and the inanimate, the complete autonomy of vital pheno-
mena.
Borodin continued:
That old woman, the life force, whom we buried with such
triumph, at whom we mocked in every way, was only pretending
to be dead and now decides to demand some rights to life,
prepares herself to start up in a new form. . . . Our expiring nine-
THE WORK OF PASTEUR 33
teenth century misses fire, it misses fire on the question of the
origin of life.
Thus idealism, which, as we have already seen, argued
obstinately throughout its whole history in favour of the
existence of spontaneous generation, carried out a complete
volte face on this question at the beginning of the present
century. The triumph of the theory of evolution forced the
vitalists to regard the problem of the origin of life as the
last refuge of the ' life force '. Darwinism might well give
a materialist explanation of the ways in which higher organ-
isms develop from lower ones, but the human mind would
never be able to understand how life itself came about,
because its essence (' entelechy ', the ' life force ', the ' cellular
spirit ', etc.) lay at the limit of the capacity of the intellect.
We find this in the WTitings of most of the neovitalists and
other idealistically inclined biologists of our century. Thus
H. Driesch^^ wrote of the insolubility of the problem of the
origin of this vital principle which he called ' entelechy '.
Uexkiill" drew attention to the necessity for a special trans-
cendental factor (structural plan) for the origin of life. L.
Bertalanffy^* denied the possibility of the self-formation of
such a system as, in his opinion, an organism must be. E.
Lippmann finishes his book^ devoted to the problem of the
emergence of life with the words: "The limitations of the
intellect prevent us from penetrating into the problem of
life. . . . We cannot understand its essence which appears to
be metaphysical." Thus the idealists try to use the demoli-
tion of the theory of spontaneous generation as an occasion
for proclaiming the impossibility of solving the question of
the origin of life on a materialistic basis.
The leading proponents of materialism rejected this ap-
proach to the problem right from its inception in the last
years of the nineteenth century. They considered that the
fact that microbes do not develop spontaneously in organic
solutions and infusions was no argument that life has not a
material origin.
One of the first to discuss this problem was F. Engels.^"
He remarked that all investigations so far made in this field
had been quite limited in approach, dealing only with the
34 THEORIES OF SPONTANEOUS GENERATION
problem of plasmogenesis. Pointing out that spontaneous
generation [generatio aequivoca) was contrary to the findings
of contemporary science, Engels ironically remarked that it
would be absurd to hope to compel nature with the help
of some stinking water to do in 24 hours that for which
thousands of years had been required. Thus Engels emphas-
ised that it was not sudden spontaneous generation but a
prolonged evolution of matter which led up to the emergence
of life.
However, most scientists of that period still took up a
mechanistic position and held that sudden spontaneous
generation was not only the simplest, but even the only
conceivable explanation of the origin of life. In this connec-
tion E. HaeckeP" wrote " To deny spontaneous generation
means to accept a miracle, the divine creation of life. Either
life arises spontaneously on the basis of some particular laws,
or else it has been produced by supernatural forces." This
kind of conviction explains the zeal with which many of the
exponents of mechanistic materialism flew in the face of the
facts to demonstrate the possibility of spontaneous genera-
tion. They saw no other way out. As an example one may
mention the violent but ill-founded attacks made by the
talented Russian publicist D. Pisarev" on the work of
Pasteur.
Finally, there was no dearth of experimental effort to show
that it was possible for living creatures to come into existence
suddenly. However, all these experiments, without excep-
tion, were utterly futile. The most serious and interesting
were those of Bastian.'^ He showed that micro-organisms
developed in boiled infusions of hay even when the flasks
containing the infusions were opened on mountain tops or
after the air entering them had been brought to a red heat.
The investigations of Pasteur were consistent with the factual
side of these experiments but Pasteur also showed that spon-
taneous generation of microbes had not occurred in this case
either. The spores of the hay bacillus, which was the organism
which grew, can withstand prolonged boiling and still remain
viable. If the hay infusion is heated in an autoclave to
120° C or boiled twice it, like other organic liquids, will
retain its sterility on the admission of uninfected air. In such
THE WORK OF PASTEUR 35
cases repeated boiling acts as follows: the first heating
destroys all the vegetati\e forms of the bacteria but the spores
remain. After cooling, bacteria develop from the spores but
succumb to the second boiling without having succeeded in
forming new spores.
The outstanding Russian scientist K. A. Timiryazev, with
his usual clarity of scientific exposition, submitted these
attempts to demonstrate the possibility of spontaneous genera-
tion to devastating criticism. In an address which he delivered
at a session of the Society of the Friends of Science in 1894
he spoke as follo^vs :
When Bastian created bacteria from an infusion of turnips
with rotten cheese in the nineteenth century he was, in this
matter, just as much of an empiricist as was van Helmont in the
sixteenth century, when he created mice from flour and dirty
rags. At least I know of no physical or chemical laws which
might lead one to prefer the stinking mixtures of the nineteenth
century empiricists to the sluttish mixtures of the sixteenth
century one. Attempts to produce spontaneous generation in the
nineteenth century are not necessarily superior to such attempts
made in the sixteenth century ; in fact, they are equally far from
the basic ideas which characterise the scientific thought of our
times.
Furthermore, while arguing with Borodin, Timiryazev
declared :
So you pick out two or three foolhardy adventurers with the
ideas and mentality of the sixteenth century, going astray in the
middle of the nineteenth century ; you see in them the represen-
tatives of contemporary science and hail their failure as the
' misfiring of the nineteenth century '. Is that quite fair?*
563
This impassioned reply by Timiryazev is also fully applic-
able to the empiricists of the present day, the adherents of
spontaneous generation who, according to their way of think-
ing, are rushing to the defence of materialism and who only
delude themselves and others with their experiments. Having
been concerned with the problem of the origin of life for
many years, I have received and still receive a large number
of letters 'with descriptions of different instances of spon-
36 THEORIES OF SPONTANEOUS GENERATION
taneous generation which is said to have occurred in the
experiments of one or another of the writers. However, none
of these experiments need be taken seriously. They are
amateurish and the sources of error can easily be established.
From the works on spontaneous generation which still
appear from time to time in the scientific literature, one
may be selected by way of an example because it concerns
the scientist F. Elfving, who is well known for his investiga-
tions in the field of microbiology. It was published in 1938
in the journal of the Finnish Scientific Society.'* Elfving
sterilised dried peas by placing them in a solution of corrosive
sublimate (3 : 1000) for half an hour ; he then washed them
with sterile water and allowed them to germinate under
sterile conditions in Erlenmayer flasks containing a little
water. When the peas grew and the sprouts had developed
considerably he killed them by keeping the flasks at a tem-
perature of 60° C for one to two hours. Some days after this
treatment by heat he noticed that the water in which the
dead plants were lying was swarming with bacteria. From
this experiment Elfving came to the conclusion that, in the
dispute between Needham and Spallanzani, it was Needham
who was right. The substance of the peas which had been
killed by gentle heating contained a special ' generative
power ' which gave rise to new living bacteria. It is easy
to detect Elfving's mistake. As was shown by investigations
on the production of sterile cultures of higher plants, particu-
larly the experiments of G. Petrov,*^ one can never success-
fully sterilise seeds by keeping them for this or that time in
a solution of corrosive sublimate. This is better achieved by
the action of a solution of bromine. There can be no doubt
that completely viable germs remained on the surfaces of
Elfving's peas. Elfving himself remarked that on the peas
" there grew mycelia which were obviously derived from
some spore which had survived the treatment with corrosive
sublimate". On repeating Elfving's experiments, using
bromine instead of corrosive sublimate to sterilise the peas,
we were easily able to convince ourselves that under these
conditions, as was only to be expected, no development of
microbes occurred.
THE WORK OF PASTEUR 37
We even find an attempt to rehabilitate Pouchet's experi-
ments and thus to resuscitate the theory of spontaneous
generation in the much pubHcised book of O. Lepeshinskaya,
The development of cells jwm living matter.^^ How-
ever, no such attempts have withstood criticism by experi-
ment and, as Terekhovskii pointed out long ago, they are
foredoomed to failure. The organisation of any of the living
creatures known to us, even the simplest ones, exhibits not
only a very complicated structure in the protoplasm, a par-
ticular arrangement in space of those molecular complexes
which constitute the protoplasm, but also organisation in
time, a particular series of biochemical processes which,
together, constitute the metabolism. We now know very
well that even relatively slight interference can produce far-
reaching changes in such a system. On damaging protoplasm
mechanically or by heat the balance of the metabolism is
disturbed irreversibly. This disturbance upsets the har-
monious interaction of the synthetic processes and markedly
intensifies the reactions of breakdown which proceed in a
disorderly way.
It is interesting to note that the hypothesis of spontaneous
generation was always applied to those organisms which had
only been studied imperfectly at each stage of the develop-
ment of science. Before Redi's experiments it was applied to
various kinds of worms and parasites. It was the same with
bacteria before the time of Pasteur. Finally, in our own
times, an attempt has been made to resurrect the theory of
spontaneous generation with reference to organisms dis-
covered during this period but still poorly understood, the
ultramicrobes and filterable viruses. However, this attempt
has been a complete fiasco too.
Summing up all that has been said in this chapter, one
must emphasise that the very idea of spontaneous generation
has been based on faulty observations, accepted uncritically,
of the sudden appearance of living creatures in nature or in
the laboratory. The possibility of spontaneous generation was
assumed by philosophers of every school and persuasion
throughout the course of many centuries. They only quar-
relled about the theoretical interpretation of the ' pheno-
menon '. However, as the methods of scientific investigation
38 THEORIES OF SPONTANEOUS GENERATION
ot living nature became more and more precise, spontaneous
generation was gradually relegated to simpler and simpler
organisms. Finally the sudden appearance of even the most
primitive organisms from inanimate material was shown to
be impossible. Thus, to-day, the theory of spontaneous genera-
tion has no more than a historical interest and cannot serve
as an approach to the problem with which we are concerned.
BIBLIOGRAPHY TO CHAPTER I
1. E. O. v. LipPMANN, Urzeugung und Lebenskraft. Berlin,
1933-
2. J. G. Crowther. Science unfolds the future. London, 1956.
3. William Shakespeare. Antony and Cleopatra. Act 2,
Scene 7.
4. A. Makovel'skii. Dosokratovskaya filosofiya. Pt. 1, Vol. 1.
Kazan, igi8.
5. Paul Tannery. Pour I'histoire de la science hellene. De
Thales a Empedocle. Paris, 1930 (2nd edition by
A. Di6s).
Theodor Gomperz. Griechische Denker. Geschichte der
antiken Philosophie. 3rd edition. Vol. 1. Leipzig,
1911-
6. A. Deborin. Kniga dlya chteniya po istorii filosofii. Vol. 1.
Moscow (Izd. Novaya Moskva), 1924.
Democritus. Fragments.
7. Epicurus. Letter to Herodotus.
8. Lucretius. De rerum natura.
. 9. RoDEMER. Lehre von der Urzeugung hei den Griechen und
Romern. Dissert. Giessen, 1928.
10. Aristotle. De generatione animalium.
11. E. Zeller. Die Philosophie der Griechen. Leipzig, 1923.
12. Apuleius. Metamorphoses.
13. H. Meyer. Geschichte der Lehre von den Keimkrdften.
Bonn, 1914.
14. St. Basil. Hexaemeron. Cf. A select library of Nicene and
Post-Nicene Fathers of the Christian Church. 2nd
series. Vol. 8. St. Basil : Letters and select loorks
(trans. Blomfield Jackson), p. 102. Oxford, 1895.
15. Cf. (Li).
16. Istoriya filosofii (ed. G. F. Aleksandrov, V. E. Bykhovskii,
M. B. Mitin and P. F. Yudin). Vol. 1, p. 413. Moscow
(Politizdat), 1940.
BIBLIOGRAPHY 39
17. V. I. Lenin. Filosofskie tetradi. Moscow (IMEL), 1933.
18. J. SiGHART. Albertus Magnus, sein Leben iind seine Wissen-
schaft. Regensburg, 1857.
ig. A. Shtekl'. Istoriya srednevekovol filosofii. Moscow (Izd.
Sablina), 1912.
20. F. S. BoDENHEiMER. Materialien zur Geschichte der Ento-
mologie bis Linne. Berlin, 1928.
21. DiMiTRii RosTOvsKii (D. Tuptalo). Letopis', skazuyushchaya
vkrattse deyaniya ot nacliala mirobytiya do rozJidestva
Khristova, sobrannaya iz bozhestvennogo pisaniya i iz
razlichnykh khronografov i istoriografov grecheskikh,
slavenskikh, rimskikh, pol'skikh i inekh. Quotation
from Sochineniya, Vol. 4, p. 243. Moscow, 1857.
22. Th. Prokopowicz. Christianae orthodoxae theologiae in
Academia Kiowiensi. Vol. 1, p. 51. Lipsiae, 1782.
Quoted by S. Sobol'. Istoriya mikroskopa. Moscow
and Leningrad (Izd. AN SSSR), 1949.
23. Quoted by B. Raikov. Zhurnal Ministerstva narodnago
Prosveshcheniya, [Nov. ser.] 66 (1916, no. 11) otd. 3,
P-33-
24. Quoted by E. Lippmann in (L 1), p. 39.
25. A. TscHiRCH. Handbuch der Pliarmakognosie. Leipzig,
1909-
26. Adam Olearius. (ed. H. v. Staden.) Die erste deutsche Expedi-
tion nach Persien (1635-9). Leipzig, 1927.
27. E. Darmstaedter. Acta Paracels.,Miinch., i^^i.
28. J. W. VON Goethe. Faust.
29. G. GuREV. Sistemy niira. Moscow and Leningrad (Izd. AN
SSSR), 1940.
30. W. Bulloch. The history of bacteriology. London, 1938.
31. T. Meyer-Steineg and K. Sudhoff. Geschichte der Medizin.
(2nd edition). Jena, 1922.
32. F. Bacon. Works. Vol. i, pp. 146, 150. London (Reeves and
Turner), 1879.
33. R. Descartes^ Oeuvres philosophiques.
34. F. Redi. Esperienze intorno alia generazione degV inset ti.
Firenze, 1668. Quoted in (I. 30).
35. A. VAN Leeuwenhoek. Naturs Verborgentheden Ontdekt.
Delft, 1697. Quoted by V. Omelyanskii in Osnovy
mikrobiologii. Petrograd (Gosizdat), 1922.
36. L. JoBLOT. Descriptions et usages de plusieurs nouveaux
microscopes. Paris, 1718.
40 THEORIES OF SPONTANEOUS GENERATION
37. Isioriya filosofii (ed. G. F. Aleksandrov, V. E. Bykhovskii,
M. B. Mitin and P. F. Yudin). Vol. 2, p. 202. Moscow
(Gospolitizdat), 1941.
38. G. W. Leibnitz. La Monadologie. Opera philosophica (ed.
J. E. Erdmann), p. 705. Berlin, 1840.
39. E. NoRDENSKioLD. Die Geschichte der Biologie. Jena, 1926.
40. J. T. Needham. Phil. Trans., 1749, No. 490, p. 615.
Idee sominaire ou vue generale du systeme physique
et metaphysique de M. Needham. Bruxelles, 1776.
Quoted in (I. 30), p. 74.
41. L. Spallanzani. Saggio di osservazioni microscopiche con-
cernenti il sistema della generazione dei Sig. di
Needham e Bufjon. Modena, 1765. Quoted in (I. 30),
P- 75-
42. L; Spallanzani. Opuscoli di fisica animale e vegetabile.
Modena, 1776.
43. M. TjEREKHOVSKii (Martinus Terechowsky). De chao in-
fusoria Linyiaei. Dissertatio. Argentorati, 1775.
S. Sobol'. Istoriya mikroskopa i mikroskopicheskikh issledo-
vanii V Rossii v XVIII veke. Moscow and Leningrad
(Izd. AN SSSR), 1949.
44. L Kant. Kritik der Urtheilskraft. Berlin, 1790.
45. G. W. F. Hegel. Enzyklopddie der philosophischen Wissen-
schaften. Heidelberg, 1817.
46. F. V. Schelling. Zeitschrift fiir spekulative Physik. Jena,
1800-1801.
47. L. Oken. Lehrbuch derNaturphilosophie. Zurich, 1843.
48. J. L. Gay-Lussac. Ann. Chim. (Phys.), y6, 245 (1810).
49. T. Schwann. Ann. Phys.,Lpz.,4i, 184 (1837).
50. F. ScHULZE. Ann. Phys., Lpz., ^9, 487 (1836).
51. H. Schroder and T. Dusch. Liebigs Ann., 89, 232 (1854).
52. F. Pouchet. C.R. Acad. Sci., Paris, 47, 979 (1858); 48, 148, 546
(1859); 57. 765 (1863).
53. F. Pouchet. Heterogenie ou traite de la generation spon-
tanee base sur de nouvelles experiences. Paris, 1859.
54. L. Pasteur. C.R. Acad. Sci., Paris, $0, 303, 675, 849 (i860);
5/, 348 (i860); ^6, 734 (1863). Ann. Sci. nat., 16, 5
(1861). Ann. Chim. {Phys.) [3], 64, 5 (1862). Etudes
sur la biere. Paris, 1876.
55. I. Borodin. Protoplazma i vitalizm. Mir bozhii (May p. 1,
1894).
56. H. Driesch. Geschichte des Vitalismus. Leipzig, 1922.
BIBLIOGRAPHY 4I
57. J. V. Uexkull. Theoretische Biologic. Berlin 1928 ; Die
Lebenslehre. Potsdam, 1930.
58. L. V. Bertalanffy. Theoretische Biologic. Berlin, 1932.
59. F. Engels. Dialectics of nature (trans. C. Dutt). Moscow
(Foreign Languages Publishing House), 1954.
60. E. Haeckel. Natiirliche Schopfungsgcschichte. (2nd edn.)
Berlin, 1870.
61. D. PisAREv. Podvigi evropelskikh avtoritetov. Sochineniya,
Vol. 3. St. Petersburg (F. Pavlenkov), 1909-1913.
62. H. C. Bastian. The beginnings of life. London, 1872.
63. K. TiMiRYAZEV. Vitalizm i nauka. ' Sochineniya, Vol. 5.
Moscow (Sel'khozgiz), 1938.
64. F. Elfving. Comment. bioL, Helsingf., y. No. 4 (1938).
65. G. Petrov. Usvoenie azota vysshim rasteniem na svetu i v
temnote. Moscow (Tipog. Ryabushinskikh), 1917.
66. O. Lepeshinskaya. Proiskhozhdenie kletok iz zhivogo vesh-
chestva. Moscow and Leningrad (Izd. AN SSSR),
1945-
CHAPTER II
THE THEORY OF THE
ETERNITY OF LIFE
The theory of the eternity of
life among the ancients.
It is a necessary and inevitable consequence of all idealistic
doctrines that they assume that life is eternal. Idealism sets
up, in opposition to the frail material world in which every-
thing has its beginning and its end, the eternal and unchang-
ing spirit. Living creatures are born and die, but life itself,
being a non-material principle, the essence of life, is spiritual
and hence eternal. Life is never destroyed, nor does it arise
afresh ; it only changes its external material envelope, as
it transforms inert material into living organisms.
From this point of view the principle of the eternity of
life is not incompatible with the possibility of spontaneous
generation of living creatures. As we have seen in the
previous chapter, idealists have, from ancient times, united
the two doctrines. This union was specially clearly expressed
in the doctrine of ' panspermia '. According to this, the
fertilising or life-giving principle takes the form of invisible
spiritual germs of life dispersed everywhere.
We first encounter the actual term ' panspermia ' in the
work of the ancient Greek philosopher Anaxagoras (500-428
B.c.).^ In his view, the various living creatures originate
from slimy earth when it has been fertilised with ' ethereal
germs ' (spermata) which are present everywhere. Later on,
the doctrine of panspermia acquired a markedly idealistic
character. We find it in this form in the teachings of Roman
philosophers, of * the fathers of the Christian Church ', of
the mediaeval schoolmen and of a number of more recent
natural philosophers.
4.^
44 ETERNITY OF LIFE
The works of St. Augustine of Hippo may be taken as
an example. He held that the earth is full of hidden life-
engendering forces, occulta semina, invisible, mysterious
seeds of spiritual origin, which become active under favour-
able circumstances and produce plants, frogs, birds and
insects from water, air and earth. The ' spirit of growth ',
anima vegetativa of the later scholasts, the arche of Para-
celsus and van Helmont, the ' life force ' of a number of
other authors, etc., were also of this nature.
In the middle of the seventeenth century Athanasius
Kircher^ developed his theory of panspermia, according to
which the germs of life are scattered in chaos and in all the
elements, and the various animals and plants arise as a result
of their activity. A principle similar to that of panspermia
forms the foundation for Leibnitz' teaching concerning the
immortal, ubiquitous germs of life which, in the course of
their later development, form all living things. According
to Needham, the vivifying principle ' life force ' is inherent
in every particle of organic matter and only under its for-
mative influence can micro-organisms develop in decaying
materials.
Pouchet took up an analogous position. He considered
that spontaneous generation was only possible as a result of
the action of the ' life force ' which had previously entered
the molecules of organic substances.
When the theory of spontaneous generation was exploded
towards the end of the nineteenth century the vitalists and
neovitalists quietly abandoned it, bringing to the fore the
principle of the eternity of life and emphasising the impossi-
bility that the human mind could ever solve the problem
of its origin.
The position was different for those natural philosophers
who were working on a materialistic basis. They were trying
to use the theory of the eternity of life as a way out from
what seemed to be the impasse which had been created by
Pasteur's experiments. It is clear that the theory of the
eternity of life as something which has a separate existence,
divorced from matter, is foreign and hostile to materialism.
Mechanistic materialism and, in particular, hylozoism,
assume the eternity of life, and regard it as merely a constant
NINETEENTH CENTURY DEVELOPMENTS 45
and inalienable property of matter in general. If we accept
this, the spontaneous generation of living creatures follows
ex hypothesi. If all matter is endowed with life, if there is,
in principle, no qualitative difference between organisms
and objects that are inorganic in nature, then living creatures
must inevitably arise spontaneously, even in the absence
of other living creatures. Hylozoism without spontaneous
generation is absurd. It is thus inconsistent for materialists
to make use of the theory of the eternity of life to explain
the impossibility of spontaneous generation. This leads
inevitably to idealism.
The emergence of hypotheses concerning the
eternity of life in the nineteenth century.
Clear examples of this attitude are found in the pronounce-
ments of a number of authoritative scientists of the late
nineteenth and early twentieth centuries. Many of these
scientists regarded the experiments of Pasteur as proof of
the absolute impossibility of the metamorphosis of inorganic
materials into living organisms. In 1871 the distinguished
British physicist W. Thomson, later Lord Kelvin, wrote in
this connection : " Dead matter cannot become living without
coming under the influence of matter previously alive. This
seems to be as sure a teaching of science as the law of gravita-
tion."^ Hence followed the complete autonomy of living
creatures, and consequently also life must be regarded as
eternal.
The famous German physiologist H. Helmholtz said*: " It
appears to me to be a fully correct procedure, if all our
efforts fail to cause the production of organisms from non-
living matter, to raise the question whether life has ever
arisen, whether it is not just as old as matter. . . ."
The French botanist van Tieghem wrote in his textbook^ :
" The vegetation of the earth had a beginning and will have
an end, but the vegetation of the universe, like the universe
itself, is eternal ".
We meet similar opinions among a number of other scien-
tists who, proceeding from the empirically established fact
of the impossibility of spontaneous generation, proclaimed
46 ETERNITY OF LIFE
that life is in principle eternal while still reckoning that
they had based their position on materialistic principles.
Thus, for example, the very able Russian plant physiologist
and biochemist S. Kostychev® wrote in the conclusion of his
book On the appearance of life on the Earth: "When the
echoes of the battle about spontaneous generation finally die
away, everyone will recognise that life only changes its form,
but never arises from dead matter ". However, wishing to
escape from the justifiable accusation of idealism, he added :
" It must be noted that this point of view has nothing in
common with the theory of vitalism, which is nebulous and
hostile to progress ". All the same, this denial is unconvinc-
ing, and it is not easy to see how one can combine acceptance
of the eternity of life with denial of ' the eternal vital prin-
ciple ' or ' life force '.
As early as the late nineteenth century, F. Engels^ gave
detailed consideration to the principle of the eternity of life,
and showed convincingly that it is incompatible with con-
sistent materialism. He quotes a very characteristic remark
made by Liebig to M. Wagner in 1868 :
We may only assume that life is just as old and just as eternal
as matter itself, and the whole controversial point about the
origin of life seems to me to be disposed of by this simple
assumption. In point of fact, why should not organic life be
thought of as present from the very beginning just as much as
carbon and its compounds (!)* or as the whole of uncreatable
and indestructible matter in general, and the forces that are
eternally bound up with the motion of matter in space (II. 7,
P- 390)-
Engels points out that such views can only be based on
recognition of a specific vital force, such as a ' formative
principle ', and do not at all correspond with a materialist
picture of the universe. Engels further wrote in comment :
Liebig's assertion that carbon compounds are just as eternal
as carbon itself, is doubtful, if not false. . . The compounds
of carbon are eternal in the sense that under the same conditions
of mixture, temperature, pressure, electric potential, etc., they
are always reproduced. But that, for instance, only the simplest
* Engels' italics and exclamation mark.
NINETEENTH CENTURY DEVELOPMENTS 47
carbon compounds, co^ or ch^ should be eternal in the
sense that they exist at all times and more or less in all places,
and not rather that they are continually produced anew and
pass out of existence again — in fact out of the elements and into
the elements — has hitherto not been asserted. If living protein is
eternal in the same sense as other carbon compounds, then it must
not only continually be dissolved into its elements, as is well
known to happen, but it must also continually be produced
anew from the elements and without the collaboration of pre-
viously existing protein — and that is the exact opposite of the
result at which Liebig arrives (II. 7, p. 394).
The proposition that living beings invariably arise when
certain conditions are fulfilled has nothing in common with
the concept of the ' eternity of life '. On the contrary, it
leads to the idea that organisms invariably originate from
inanimate matter.
Against this, those ^vho favour the eternity of life consider
that at all times there has existed some element w^hich has
been passed in succession from organism to organism. With-
out this the occurrence of living beings is impossible. " Life,"
wrote F. J. Cohn (1828-1898), " is like the holy fire of Vesta,
^vhich was only kept in being continuously by kindling the
new flame from the old." But what is this special principle
that is present only in the living organism, and what is
its nature? It cannot be an eternal property of matter, as
the ancient Greeks supposed, because then the vivification
of matter would not require the participation of a living
organism already in existence, but life would arise spon-
taneously of itself. It cannot be a new quality arising in
the course of the historical development of matter, because
then it Avould not be eternal. Consequently, this principle
cannot be material in nature. And so, as soon as we try
to extend or develop the principle of the eternity of life,
whether we want it or not, ^ve find ^\■e have been trapped
into idealistic assumptions. It cannot be said that attempts to
resolve this contradiction on the basis of a so-called ' material-
istic dualism ' have been successful. This recognises the
parallel and independent existence of tw^o completely autono-
mous forms of matter, radicallv distinct from one another
and separated by an impassable gulf.
48 ETERNITY OF LIFE
The well-known Russian geochemist V. Vernadskii (1863-
1945) presents the clearest example of this tendency. In his
works written in the twenties and thirties of this century
he puts forward the view that the idea " that logic demands
that there should be a beginning of life came into science as
a problem of religion and philosophy " and that it is " foreign
to the empirical foundations of science". He wrote:
None of the exact relationships between facts which we know
will be changed if this problem has a negative solution, that is,
if we admit that life always existed and had no beginning, that
living organisms never arose at any time or place from inert
material, that in the history of the earth there were no geological
periods in which life did not exist.^
Vernadskii held that the essential feature of the material
and energetic characteristics of living bodies which distin-
guishes them from inert matter is that a special orientation
is inherent in the former.^ He pointed out that even Pasteur
recognised the possibility of different states of cosmic exten-
sion and that he used this concept to explain the phenomenon
of asymmetry in living things, or, to use the terminology of
Vernadskii, * rightness and leftness '. This orientation which
is associated with individual organisms is described by Ver-
nadskii as follows : The mirror-image forms of each chemical
compound are acknowledged to be chemically identical in
inert matter and different in living organisms.
The chemical dissimilarity is thus conspicuous in the
products of biochemical processes, in which either the dextro
or laevo isomer predominates. Vernadskii further puts for-
ward the idea that this orientation in space, which is associ-
ated with the body of the living organism, is only created
in the biosphere from natural living bodies which have
existed previously, that is, as a result of reproduction. Thus
our lack of success in bringing about the synthesis of a living
thing is due to the fact that the special asymmetric spatial
conditions required for the purpose are absent from our
laboratories.
The question of the 'rightness and leftness' of living
substance deserves serious consideration and we shall return
to it later, but it must be pointed out here that at present
NINETEENTH CENTURY DEVELOPMENTS 49
a large number of facts are being reported in the scientific
literature which suggest the possibility of the production of
asymmetric substances independently of living things in the
presence of asymmetric factors acting in inorganic nature.
In one of his later works, published in 1944," Vernadskii
seems to have taken account of these discoveries and did not
refer to this difference between living and inert matter but
only emphasised the fact that they differ in isotopic composi-
tion. The fact is that as early as 1926 Vernadskii demons-
trated that the isotopic composition of the elements present
in living organisms differs considerably from that of the
elements derived from minerals and rocks. HoAvever, bio-
genic formations which arise in association with living things
or after their death, such as soils, the waters of seas, rivers
and lakes, petroleums, coals and bitumens, retain the isotopic
composition characteristic of living things. Vernadskii there-
fore held that in this case one cannot a priori deny the
possibility of transition of matter from the dead (' bio-inert ')
to the living state, ' for the atomic composition of the living
and the inert matter may here be isotopically identical '. On
the other hand, the direct transition from materials which
have not arisen biogenically to living things would seem to
be excluded on account of the profound differences in
isotopic composition. However, as these biogenic formations
(' bio-inert ' substances) only develop in the presence of
organisms a closed circle of life is set up.
One might infer from this that Vernadskii continued to
believe in the complete impassability of the gulf separating
the living from the lifeless, the complete impossibility of
the primary origin of life from inert matter. Ho^ve\er, such
a conclusion would be premature. In the ^vork Avhich Ave
have cited, Vernadskii shows convincingly, in a number of
concrete examples, that a quantitative change in the isotopic
composition of the elements " is not only characteristic of
living matter but also occurs in processes which ha\'e nothing
to do with life, as among the products of volcanic eruptions ".
The whole difference lies in the fact that changes in the
isotopic composition of the elements brought about by
organisms proceed on the surface of the earth at ordinary
temperatures and pressures, ^vhereas analogous changes in
4
50 ETERNITY OF LIFE
a lifeless medium only happen at high pressures and tem-
peratures in the depths of metamorphic formations. " The
synthesis of life ", Vernadskii continued, " requires prelimin-
ary isotopic modification of the chemical elements ". However,
as we have just seen, Vernadskii himself pointed out that
changes of this sort may occur in ordinary inert media at
high temperatures and pressures and it is therefore quite
arguable that life first originated from ordinary inert (not
biogenic) matter under conditions where it was subjected to
preliminary isotopic modification by the forces of inorganic
nature.
Thus we have seen that, as a result of prolonged and varied
studies of the question, Vernadskii abandoned the untenable
position of ' materialistic dualism ' which he previously held.
In 1944 he wrote, " In our time the problem can hardly be
treated as simply as it could be during last century when,
it seemed, the problem of spontaneous generation had been
finally solved in a negative sense by the work of Louis
Pasteur."
It is hardly necessary nowadays to demonstrate theoreti-
cally the complete incompatibility of all kinds of dualistic
views with a consistent materialism. We should, however,
analyse in detail the factual evidence which has been and
still is adduced in support of their attitude by the adherents
of the theory of the eternity of life. We should examine
how far this evidence agrees with the objective data of
contemporary science. The chief difficulty which is always
encountered by the materialistically inclined proponents of
the eternity of life is the problem of the emergence of life
on the Earth and of all those beings which inhabit the Earth.
The Earth itself does not seem to be eternal, it originated
at some time and it is therefore necessary to explain in some
way how the first organisms appeared on it without recourse
to the creative act of deity or the formative influence of
a ' life force '.
For vegetation to develop on the virgin rocks of volcanic
islands the seeds or spores of plants must have been carried
there from elscAvhere. A similar idea that viable germs from
other worlds inhabited by organisms were deposited on the
virgin earth during its development was put forward by the
NINETEENTH CENTURY DEVELOPMENTS 5I
supporters of the theory under discussion as being the only
possible explanation of the appearance of life on our planet.
But before this hypothesis is scientifically admissible it must
be shown that life is widely distributed throughout the uni-
verse, that it is to be found, not only on the Earth or within
the solar system, but also in other parts of the universe.
Furthermore, it is necessary to explain how the germs of life
could be transferred to the Earth through interplanetary and
interstellar space while remaining alive and able, under
favourable circumstances, to grow and give rise to a new
race of living things.
The bold suggestion that there might be a multiplicity of
worlds inhabited by living creatures was very clearly stated
by the great sixteenth century scientist Giordano Bruno. In
his treatise Del' infinito universo e mondi^^ he wrote, " There
exist innumerable suns and innumerable earths circling
round their suns just as our seven planets circle round our
Sun. Living things dwell on these worlds."
For a long time this idea did not spread far because it
came up against the ancient but very active anthropocentric
conviction that there is only one earth supporting life in the
universe. It was considered daring and fantastic for a scien-
tist to think that there might be many inhabited worlds.
It is only 15-20 years since the authoritative English astrono-
mer Sir James Jeans^" stated that
We know of no type of astronomical body in which the condi-
tions can be favourable to life except planets like our own
revolving round a sun. . . . Yet exact mathematical analysis
shows that planets cannot be born except when two stars pass
within about three diameters of one another. . . . The calculation
shows that even after a star has lived its life of millions and
millions of years the chance is still about a hundred thousand to
one against its being a sun surrounded by planets. . . . All this
suggests that only an infinitesimally small corner of the universe
can be in the least suited to form an abode of life.
Now, however, we cannot accept Jeans' point of view.
On the contrary, contemporary scientific findings definitely
confirm the inspired foresight of Bruno. In 1938 the Swedish
astronomer E. Holmberg^^ made careful analyses of a number
52 ETERNITY OF LIFE
of measurements of the right ascensions of stars the parallax
of which had been determined with special accuracy. He
demonstrated very small but definite oscillations with periods
ranging from one and a half to three years. These oscillations
can only be explained as disturbances caused by satellites of
comparatively small mass. It would certainly be impossible
to observe these satellites directly by means of present-day
telescopes, but there is now no doubt that there are many
stars which, like our Sun, are surrounded by circulating
planets. ^^ Twenty-five per cent of the 240 stars observed by
Holmberg give indications of the presence of small, invisible
planets. Dark satellites having masses comparable with those
of our own planets have already been discovered for many
stars, e.g. 70 Ophiuchi and 61 Cygni}^
It seems, therefore, that our solar system is not unique.
There can be no doubt that planets revolve round other
stars too, and very many of these are comparable with our
Earth. There is therefore nothing to hinder us from suppos-
ing that life exists on some of them, maybe even on many
of them.
In his book Lije on other worlds H. Spencer Jones^*
analyses a great deal of factual material relating to our prob-
lem and arrives at the conclusion that life is distributed
throughout the universe and that the number of worlds
where life is possible seems to be very considerable (see also
the recent book of A. Oparin and V. Fesenkov, Zhizn' vo
vselennoi* Moscow (Izd. AN SSSR), 1956). Thus the first
condition mentioned above for the acceptance of the theory
under discussion, that is to say the wide dispersal of life in
the universe, is not ruled out by the findings of contemporary
science. The case is, however, different as regards the passage
of the germs of life through space.
The hypotheses concerning this problem may be divided
into two groups, (1) the transport of the germs by meteorites
(' cosmozoe ' or ' lithopanspermia ') and (2) transport of the
germs with cosmic dust under the pressure of light (' radio-
panspermia ').
* Life in the Universe. — Translator.
COSMOZOE 53
The theory of cosmozoe.
The idea that fragments of stars bearing the seeds of life
might reach the Earth and thus impregnate it was discussed
as far back as the beginning of last century by the French-
man de Montlivault.^" It was later developed by H. Richter^*
in 1865. He started from the hypothesis that when celestial
bodies are in rapid motion small pieces or solid particles may
become separated or torn off from them. It might be that
the viable germs of micro-organisms were attached to the
particles at the time when they became separated from the
celestial bodies. Furthermore, these particles would wander
in interstellar space and might, by chance, arrive on other
heavenly bodies. When these germs fell on a planet where
the conditions were favourable for life (suitable conditions
of moisture and temperature) they would start to develop
and, in the course of time, they would establish themselves
as the ancestors of all living things on that particular planet.
Richter assimied that somewhere in space there are always
celestial bodies on w^hich life exists in the form of cells. This
idea was later developed by M. Wagner,^^ who considered
that " the atmospheres of the heavenly bodies, and also the
swirling cosmic mists may be regarded as eternal repositories
of living forms, as perpetual plantations of organic germs ".
Thus life is scattered throughout the universe and travels in
the form of germs within meteorites.
Richter paid special attention to the possibility that viable
germs might be carried through interstellar space. He
pointed out that the germs of living things can exist for long
periods without nutrients and water, remaining in a more
or less inanimate state, and may then rea^vaken to a new
life, though only when the necessary conditions are fulfilled.
As a result of this capacity they may make very long journeys.
The only hazard to which the germs of life are submitted
arises from the increase in temperature which occurs as a
result of the tremendous friction generated between the
meteorites and the atmosphere of the Earth. However,
Richter points out that some meteorites contain traces of
carbon and other easily combustible substances. If these
substances can reach the Earth without being burnt, it is
54 ETERNITY OF LIFE
perfectly possible that germs might pass through the atmo-
sphere without losing their viability.
Similar views were put forward in Britain by Lord Kelvin,^
who wrote in 1871 :
Should the time when this Earth comes into collision with
another body, comparable in dimensions to itself, be when it is
still clothed, as at present, with vegetation, many great and
small fragments carrying seed and living plants and animals
would undoubtedly be scattered through space. Hence and
because we all confidently believe that there are at present,
and have been from time immemorial, many worlds of life
besides our own, we must regard it as probable in the highest
degree that there are countless seed-bearing meteoric stones
moving about through space.
These statements made a very great impression on the
scientists of those times. In Germany they were supported
by H. Helmholtz,^" who considered that the germs of life
had reached the Earth by means of meteorites which, in
their passage through the atmosphere of the Earth, had been
strongly heated on the surface only, while the inner part
remained cool. In France this opinion was shared by van
Tieghem, who wrote that the Earth received the seeds of life
by their being carried on meteorites ; henceforth it con-
served the life which was derived from these original germs.
The main foundation for all these hypotheses was the
fact that many rocky meteorites contain compounds of
carbon approaching hydrocarbons in their composition. For
example, chemical analyses by Cloez'^ of the Orgeuil meteor-
ite revealed the presence of amorphous substances very simi-
lar to the humus-like substances found in some fuels dug
from the earth. At the time when the presence of hydro-
carbons in meteorites was first discovered people were still
convinced that organic substances, including hydrocarbons,
could only be formed under natural conditions in living
cells. Many scientists therefore supposed that the hydro-
carbons found in the meteorites had been formed there
secondarily as the result of the decomposition of organisms
which had lived at some time on these heavenly bodies. This
raised the question of the possible existence of living bacteria
or their spores inside the meteorites.
COSMOZOE 55
Nowadays, since the comprehensive investigations of D.
Mendeleev-^ and other chemists, we know that hydrocarbons
and their derivatives can easily develop inorganically under
natural conditions, particularly from cohenites, which are
minerals commonly found in meteorites and composed of
carbides of iron, nickel and cobalt — (Fe, ni, €0)30.
J. L. Smith^^ showed that the organic substances found in
the Orgeuil and other meteorites could have been formed
as the result of reactions between iron carbide and iron
sulphide. From the Orgueil meteorite Smith even prepared
compounds of carbon, hydrogen and sulphur such as C4H6S5.
He showed that there is no foundation for the belief that
these organic compounds have been formed by organisms.
Berthelot and Schutzenberger independently reached simi-
lar conclusions. They demonstrated in meteorites the pres-
ence of hydrocarbons completely analogous to those formed
during the smelting of iron at temperatures which are
certainly incompatible with life. Thus the discovery of
compounds of carbon in meteorites cannot now serve as an
argument that there are traces of life on these bodies.
Neither have numerous attempts to discover directly the
germs of microbes on meteorites given definite positive
results. S. Meunier-* stated that Pasteur, whom he supplied
with specimens of carbon-containing meteorites, also tried
to isolate viable bacteria from them. He even constructed
a special boring apparatus for the purpose, which enabled
him to take specimens from the inner parts of the meteorites.
However, Pasteur always got negative results and therefore
did not publish them. Later scientists have had no more
success in finding living things in meteorites.
The only exception is to be found in a publication by
C. B. Lipman^^ in 1932. Here the author describes his
investigations made on many specimens of stony meteorite.
He sterilised the outside of the meteorites and took measures
to exclude contamination by adventitious bacteria. Never-
theless he was often successful in obtaining living bacteria
in the form of rods or cocci by sowing broken-up pieces of
the meteorite on a nutrient medium.
This communication attracted much attention in scientific
circles and even found its way into some textbooks (e.g."),
56 ETERNITY OF LIFE
but unfortunately it has not been confirmed up till now. It
is worthy of note that the microbes obtained by Lipman
seemed to be identical with the ordinary terrestrial bacteria.
In view of the great variability of bacteria and the readiness
with which they adapt themselves to external conditions, it
is hard to believe that exactly the same forms of micro-
organisms exist on other heavenly bodies as on our planet.
It seems far more probable that, in spite of all his precautions,
Lipman failed to prevent terrestrial bacteria from falling on
to the meteorites he was studying while he was grinding
them. In a letter which he sent to me, Lipman himself did
not insist that his results were completely unequivocal.
In the present state of our knowledge it is, in fact, hard
to suppose that organisms are present inside meteorites. If
life had developed at some time and place on the planet from
which the meteorite had become separated, it would un-
doubtedly have left traces in the shape of biogenic forma-
tions. However, even after the most careful searches nobody
has been able to find traces of such formations anywhere in
meteorites. According to A. Fersman, F. Levinson-Lessing
and others there is nothing resembling a sedimentary
formation nor anything which might, in general, be ascribed
to biological processes. Mineralogical studies of meteorites
also show that they were formed under conditions incompat-
ible with life.
That great expert on meteorites Vernadskil wrote as fol-
lows" :
Those germs of life, ' microzoa ', cannot have any connection
with meteorites or any cosmic dust known to us. For nowhere
in the structure of the meteorites or dust do we see manifesta-
tions or effects of life. If we study them we find that they were
formed under conditions similar to those under which our own
deepest formations originated (high pressure and high tempera-
ture) or else by chemical processes from liquids and gases, also
at high temperatures (chondrites, moldavites). Microbes may be
associated with them fortuitously but are quite independent and
not directly connected with them.
Thus the only possibility would be that the microbes
might be picked up by the meteorites in space, but they
PANSPERMIA 57
would then certainly be on the surface of the meteorites and
would therefore necessarily be destroyed in transit through
the Earth's atmosphere.
A very bold and original hypothesis has fairly recently
been put forward by L. Berg."* It is directly connected with
the meteoritic theory of the transport of life. Berg bases his
hypothesis on O. Shmidt's meteoritic theory of the formation
of the Earth. ^^ According to this theory, the Earth was never
an incandescent sphere but consisted of cold materials from
the beginning. "Along with the aggiegation of meteorites
of which it is formed ", Berg wrote, " the Earth may also have
acquired the germs of life or perhaps ready-made complex
living organisms."
This hypothesis, however, agrees so badly with the facts
so far studied that it is hard to point to a single fact which
might support it. On the contrary, all that we know about
meteorites and cosmic dust is totally opposed to it.
Summing up all that has been said, we must admit that
the theory of cosmozoe or lithopanspermia, the theory that
life arrived on Earth inside meteorites, is in direct contradic-
tion to the objective facts of contemporary science.
Arrhenius' theory of panspermia.
The theory of radiopanspermia was produced at the begin-
ning of the twentieth century to replace that of litho-
panspermia. The originator of this theory was the famous
Swedish physical chemist S. Arrhenius,^" who was an ardent
supporter of the idea that life is distributed throughout
space. He tried to prove by direct calculations that it is
possible for particles of matter to pass from one heavenly
body to another. He considered that the main agent in this
case would be the pressure of the rays of light.
The phenomenon received its theoretical foundation at
the hands of Clerk Maxwell in the second half of the nine-
teenth century, but the scientists of that time refused to
accept it without direct experimental evidence. Only a bril-
liant experimentalist like the Russian physicist P. Lebedev^^
could succeed in demonstrating the phenomenon, which he
did in 1900. By direct experiment Lebedev showed that
LIGHT
58 ETERNITY OF LIFE
light exerts pressure on those objects on which it falls and,
furthermore, he determined the magnitude of this pressure.
>N^ It turned out to be infinitesi-
/ ^ mal. The sunlight falling on
' * the surface of the Earth only
exerts a pressure equivalent to
0-5 mg/m^, but even this is
enough to cause minute par-
ticles of dust to move through
a vacuum at a considerable
speed.
Fig. 1 is a diagram illustrat-
ing the experiment of Nichols
and Hull which demonstrates
UGHT f]^e theory well. They used a
LIGHT glass vessel shaped like an hour
glass. In it they placed a
mixture of emery and very fine
carbon dust obtained by the
carbonisation of fungal spores.
The air was evacuated from the
vessel. The stream of particles
falling through the narrow
opening was illuminated by a powerful source of light. The
emery fell to the bottom but the carbon particles were
diverted on to the walls.
Arrhenius drew a picture of the passage of small particles,
among them the spores of micro-organisms, through inter-
planetary and interstellar space. Upward currents of air,
which would be specially strong after volcanic eruptions,
might carry particles of matter to very great heights, up to
100 or more kilometres above the surface of the Earth. In
the upper layers of the atmosphere there are, for a number
of reasons, constant electrical discharges which would be
more than enough to drive these particles of matter out of
the atmosphere of the Earth into interplanetary space. Here
the particles \sould travel further and further under the
one-sided pressure of the rays of the Sun.
As from the surface of the Earth so, in the same way, very
small particles must be constantly becoming detached from
Fig. 1. Diagram of the experi-
ment of Nichols and Hull.
PANSPERMIA 59
the surfaces of other heavenly bodies. If a planet is inhabited
by living organisms, particularly micro-organisms, then their
spores would be able to travel through interstellar space in
the same way. Arrhenius calculated that bacterial spores
having a diameter of 00002-0000 15 mm could travel through
space at a very great speed under the influence of the pressure
of sunlight. Fourteen months after having left the Earth
such a spore would pass out of our planetary system, but it
would be 9,000 years before it reached the nearest star,
a Centauri. The migration of spores can, however, take place
towards the Sun as well as away from it. While wandering
in interstellar space the germ may meet comparatively large
particles of cosmic dust. If the spore becomes attached to a
particle having a diameter of 0-0015 mm it will begin to
move towards the Sun, as the pressure of the light will not
be able to overcome the weight of the particle which will
be approaching the Sun under the influence of gravity.
Arrhenius thought that the Earth might have been colonised
in this way by spores of micro-organisms coming into our
solar system from other parts of the universe.
According to the calculations of Arrhenius the particles
of cosmic dust falling on the Earth in this way would not
necessarily get hot and burn in the atmosphere of the Earth
as do meteorites. If the particles were of the size mentioned,
the pressure of light would check their motion and the speed
at which they fell would be slow enough for them only to
be heated through some tens of degrees, which would not
prevent the spores from retaining their viability.
Arrhenius' theory received wide attention in the scientific
world and found many supporters both among physicists
and among biologists. In the U.S.S.R. in particular it was
supported by S. Kostychev, P. Lazarev, A. Nemilov'^" and
others. In fact, Arrhenius made careful enough calculations
and a good analysis of the mechanical aspect of the passage
of particles of matter from one heavenly body to another.
There remained, however, the unsolved problem of whether
the germs of bacteria could accomplish such an interstellar
journey and remain alive. To this aspect of the matter
Arrhenius and the other supporters of his theory quite
naturally paid special attention.
6o ETERNITY OF LIFE
The distance separating one planetary system from another
is tremendous. Even if the particles were to travel at the
speed already mentioned it would still be many thousands
of years before they reached the nearest star. Under these
circumstances one must take into consideration all the
dangers to which the germs of life would be submitted
during the whole course of their long journey, the severe
cold of interstellar space, the complete absence of moisture,
oxygen, etc. Could they endure all these hardships for thou-
sands of years while still retaining the ability to multiply
when they fell on a new planet, and to give rise to all the
later inhabitants of that planet?
The state of the problem
at the present day.
The adherents of panspermia expended much work and
ingenuity to prove the possibility of such a passage of the
germs of life from one heavenly body to another in a viable
condition. The spores of bacteria are, in fact, extremely
stable under all sorts of unfavourable external conditions.
Many of them certainly do not need oxygen. It is well known
that anaerobic bacteria can not only be conserved without
oxygen but can live without it for the whole of their lives.
In the absence of water due to partial, or even more so
to complete, drying, living processes are brought to a stand-
still but the organism is not by any means always killed.
It only goes into a state of anabiosis. This is generally known
in the case of the seeds of plants and even such lower animals
as rotifers, tardigrada and eelworms. The extensive literature
concerning this question is collected in P. Shmidt's book
Anabiosis. ^'^ The spores of bacteria are particularly resistant
to drying. At the beginning of the century L. Maquenne^"*
showed that it is even possible to keep absolutely dry seeds
in a vacuum for many years and that under this treatment
they do not lose their viability. This was later confirmed by
P. BecquereP^ and a number of other authors.
The resistance of bacteria and their spores to low tempera-
tures appears to be exceptional. R. Pictet^* pointed out
this peculiarity of bacteria in the nineteenth century. P.
PRESENT STATE OF THE PROBLEM 6l
Becquerel" kept ampoules containing the dried spores of
moulds and bacteria in a vacuum at the temperature of
liquid air for several weeks. They all remained alive and
grew for a year and a half under observation. The articles
of C. B. Lipman^* and E. Kadisch^^ may also be referred to.
The studies of B. J. Luyet*" and his colleagues are of par-
ticular interest. These studies show that if protoplasm is
frozen deeply and quickly with liquid air or hydrogen it
is possible to avoid crystallisation of ice and the dispersal
of molectdes and disturbance of structure associated with it.
The protoplasm gets into a glassy state (becomes vitrified)
and can be kept in that form at low temperatures indefinitely
w^ithout losing the ability to be brought to life again when
transferred to favourable conditions. From this one may
conclude that the germs of bacteria which exist in inter-
stellar space, where the temperature is near to absolute zero,
could certainly float around for thousands of years without
losing their viability. We find in the literature some reports
of the survival of viable bacteria for very long periods in
the frozen state, but not all of these reports seem completely
reliable. We must refer first to the work of V. Omelyanskii.*^
He found many kinds of micro-organisms (^vhich grew on
broth media) in the tissues and mucus of the preserved middle
part of the trunk of the Sanga Yurakh mammoth, which
was sent to him from the place where the animal was found.
The author does not exclude the possibility that some of the
bacteria found in the corpse of the mammoth had reached
it later. He considers that the evidence in favour of the
microflora of the trunk being of contemporary origin with
the mammoth is more convincing. If this is true, these
bacteria have retained their viability during continuous
refrigeration for tens of thousands of years. It must, how-
ever, be borne in mind that the remains of the mammoth
were sent to Omelyanskii from a distance and were not
removed by professional microbiologists. One cannot, there-
fore, exclude the possibility that they were secondarily in-
fected.
The same applies to the observations of P. Kapterev.*- He
has drawn up a complete list of algae, fungi, bacteria and
even crustaceans which he has succeeded in bringing to life
62
ETERNITY OF LIFE
lOOKm. I ROCKET
I
from samples of frozen subsoil obtained from a depth of two
to seven metres. This implies growth after 1,000 to 3,000
years of refrigeration. L. Kriss" studied the frozen subsoil
of Kolyuchin and Wrangel
Islands and made some very
cautious inferences. Although
he too found viable micro-
cocci at these levels he con-
sidered it perfectly possible
that these had fallen there
from the upper levels where
they were also present.
Thus the problem of the
possibility of micro-organisms
being preserved in a viable
state at low temperatures for
thousands of years cannot be
considered to be conclusively
solved. Nevertheless, one
cannot reach the opposite
conclusion that bacteria and
their spores would necessarily
be destroyed at temperatures
near to absolute zero.
It seems, however, that the greatest menace to bacteria
and their spores in outer space is not so much the cold as
the radiations which pass through it. Even at the end of
last century it was established that by no means all the
radiations of which sunlight is composed reach the surface
of the Earth. Part of the light is absorbed by the atmosphere.
This absorption affects particularly the ultraviolet radiations
which are invisible to the eye but are very active chemically.
Only radiations having a wavelength of not less than 3,000 A
reach the surface of the Earth. It is only by going up high
mountains that one can establish the presence of ultraviolet
light with a wavelength of 2,900 A. All the short-wave radia-
tion is absorbed by the atmosphere and does not reach the
surface of the Earth. However, outside the atmosphere, inter-
planetary and interstellar space are penetrated by radiations
having wavelengths of 1,000-2,000 A. These radiations are
40 Km. •
BALLOON SOUND
50 Km. ■
OZONE LAYER
CIRRUS CLOUDS
20 Km. •
STRATOSTAT
AEROPLANE
10 Km. ■
MT EVEREST
Fig. 2.
Diagram of levels of the
atmosphere.
PRESENT STATE OF THE PROBLEM 63
chemically extremely active. On reaching the outer layers
of the atmosphere they are absorbed by molecular oxygen,
as a result of which the oxygen is converted into ozone. At
a height of about 30 kilometres above the surface of the
Earth there is a layer of ozone in the atmosphere called the
* ozone screen ' which shields us from the short-wave radia-
tions of interplanetary space (Fig. 2). It was noticed as long
ago as 1877 that sunshine has a harmful effect on many
bacteria. It was later established that this effect is mainly
Fig. 3. The action of ultraviolet radiations on bacteria.
Living bacteria on the left.
due to the ultraviolet part of the spectrum ^vhich has a wave-
length of less than 3,100 A. Using artificial ultraviolet light
from a mercury lamp, it was shown that the bactericidal
activity of ultraviolet radiations increases as the wavelength
decreases. It reaches a maximtun at a wavelength of about
2,700-2,800 A, and then falls off somewhat till the wavelength
is about 2,600-2,400 A, after which it again increases strongly
on passing to still shorter wavelengths. In the course of a
few minutes, or even seconds, light of this sort will destroy
not only the bacteria known to us, but also their spores
(Fig. 3)-^*
Arrhenius knew^ about the bactericidal effect of sunlight
but he considered that it was not the light itself that killed
the bacteria but the oxygen which had been activated by
it. This idea seemed to be fully confirmed by the experi-
ments of Roux and Duclos, who kept spores in glass test
tubes without oxygen under intense illumination for months.
A considerable proportion of the spores retained their viabil-
ity under this treatment.
These experiments suffered from a technical fault in that
all the ultraviolet radiation was absorbed by the glass walls
64
ETERNITY OF LIFE
of the test tubes. The experiments of P. Becquerel*^ were
technically sounder. He dried the spores of moulds, bacteria
and other micro-organisms and collected them on a glass slide
which was placed in a wide test tube. This was then hermeti-
cally sealed at the top by a plate of quartz, and then evacu-
ated and plunged into a vessel containing liquid air. The
100
90
80
,— 70
t 60
vt
z
u
I-
? 50
111
>
u
40
30
20
10
/ 1
/ 1
* A A , SMITHSONIAN PHYSICAL TABLES (FOWLE, 1934b)
\}\ O, SMITHSONIAN INST, 1920-1922 (ABBOTT 1?/ (7/, 1922)
/jf
1 r 1
\\ • , PETTIT, 1940
- Ti
^\ A , NRL,55KM, 1947 (HULBURT, 1947)
?\ , GOTZ AND SCHONMANN, 1948.
^°\ , MOON, AVERAGE TO 1940
- 1.*
\ \ /-/^j^^o.^ narMA-T-ir\ki
•A
o \
11
V\
I
^k
'
^
"'
X
Uj
^^o
h
>«
- A
~— ~ o
*' 1
1 1 1 1 . I .... 1 1 1 1 1
0.2
04
06
0.8
1.0
1.8
2.0
2 2
2.4
2.6
1.2 1.4 1.6
WAVE LENGTH, /Z
(i/i = 10,000 A = 00001 cm.)
Fig. 4. Solar spectrum curves on top of the atmosphere.
By permission from Radiation Biology, vol. ii by
A. HoUaender. Copyright 1955, McGraw-Hill Book
Company, Inc.
spores were then irradiated with a mercury lamp through
the quartz plate. They were all destroyed after fairly short
periods of exposure.
The supporters of panspermia brought forward numerous
objections to these experiments. It was suggested that there
are forms of bacteria which are specially resistant to ultra-
violet light ; that the bactericidal effect of the ultraviolet light
is due to oxidative or other chemical changes so that it can
PRESENT STATE OF THE PROBLEM 65
only manifest itself in the presence of water and oxygen
(these are absent in outer space) ; that the intensity of the
radiations was less in space than in the experiments ; that
ultraviolet radiation was not effective at temperatures near
to absolute zero, etc.
120
2500 3000
WAVE LENGTH, A
3500
Fig. 5. Ultraviolet portion of the solar spectrum on
top of the atmosphere.
By permission from Radiation Biology, vol. 11 by
A. Hollaender. Copyright 1955, McGraw-Hill Book
Company, Inc.
These objections, however, did not stand up to strict
experimental testing. At the present time direct experi-
ments using rockets which are sent up to heights of loo
kilometres, i.e. considerably above the ozone screen, have
shown that, at this level, ultraviolet radiation is far more
66 ETERNITY OF LIFE
intense. We can deduce a curve relating intensity with wave-
length for the ultraviolet radiation at the limit of the atmo-
sphere of the Earth (Figs. 4 and 5).'*^
In his review D. E. Lea'*^ also presented a wide range of
material showing that all forms of microbes and spores which
have been investigated in this respect are destroyed by the
action of short-wave ultraviolet light. We now possess con-
siderably greater factual material but it completely confirms
the earlier work on the destruction by ultraviolet light of all
forms of micro-organisms whatever their species.^^
Thus the earlier findings of R. Wiesner*^ that there exist
forms of bacteria which are resistant to ultraviolet light were
not confirmed by later workers. On the contrary, it is now
asserted that the various species only differ very slightly from
one another in their resistance. This effect of light is quite
different from that of temperature, for we know many very
thermostable bacteria. This difference is particularly notice-
able where spores are concerned. Thus, for example, the
spores of Bacillus anthracis and B. suhtilis are very resistant
to high temperatures and, in contrast to their vegetative
forms, can even undergo more or less prolonged boiling.
However, the difference in resistance between the vegetative
forms and spores does not exist in respect of the effect of
ultraviolet light, which destroys both forms of these organ-
isms almost equally easily.
Another difference between the effects of temperature and
light is that the presence of water is not necessary for the
effect of light. It has now been established that completely
dried cultures and spores of various microbes always exhibit
considerable radiosensitivity.^" Neither does oxygen seem
necessary for the bactericidal activity of light. The earlier
view that the effect of ultraviolet light depended on an
oxidative activity seems to be untenable. It has been shown
experimentally that short-wave radiations can have a destruc-
tive effect on micro-organisms even in the absence of gaseous
oxygen in the surrounding medium. Ultraviolet radiation
is bactericidal by virtue of its direct action on the substance
of the bacteria.
PRESENT STATE OF THE PROBLEM 67
Neither does the temperature play a decisive part in the
process with which we are concerned. F. Gates^^ showed that
the temperature coefficient does not exceed i-o6 in such
processes, which is as expected for photochemical reactions.
As w^e have seen, the experiments of P. Becquerel demons-
trated the bactericidal activity of ultraviolet radiation even
at the temperature of liquid air. This has been confirmed
many times since then. In this connection the recent experi-
ments of E. GraevskiP^ are of special interest. This author
was studying different forms of bacteria, moulds, yeasts and
other such organisms. He showed that when they have been
cooled to very low temperatures and the protoplasm is in
a glassy state it retains its viability for a long time because,
under these conditions, there is no need for metabolic pro-
cesses to maintain its dynamic structure. However, even
under these conditions, micro-organisms and their spores are
quickly destroyed by ultraviolet and /3-radiation. Graevskii
writes :
The effect of ultraviolet radiation on a living substrate is the
same at room temperature and at — 192° C and this completely
justifies one in assuming that even the very low temperature
prevailing in outer space could not protect living protoplasm
from the harmful effects of radiant energy.
The bactericidal effect of short-wave ultraviolet radiation
is explained by its extremely strong chemical effects. The
energy of this radiation is so great that it can alter or even
disrupt any organic molecules which absorb it. It polymer-
ises acetylene, anthracene and many other hydrocarbons. It
decomposes acetone and various aldehydes, organic acids, etc.
The effects of such radiations on proteins are particularly
interesting to us.
A. D. McLaren has summarised the work of a number of
authors in his review. ^^ Proteins are denatured under the
influence of ultraviolet light and when this happens they
lose their solubility in water, they change their viscosity,
their optical rotation and their content of amino and other
functional groups. In contrast to the denaturation caused
by heat, this alteration may occur even on irradiation of the
protein in the dry state. Its occurrence is independent of
68 ETERNITY OF LIFE
the presence of oxygen.^* These changes in the physical
properties of protein solutions which occur during irradia-
tion (changes in viscosity, solubility, etc.) depend on chemical
and structural alterations in the actual molecules of the
protein occurring under the influence of the light. These
changes are particularly marked at wavelengths where the
absorption by proteins is particularly intense. It is specially
significant that the curve for the absorption of ultraviolet
radiation by proteins corresponds closely with the curve for
the destruction of bacteria by radiation in different regions
of the ultraviolet spectrum. Thus, in both cases there are
maxima at about 2,700 A ; below this, the absorption by
proteins and the bactericidal activity fall off and then again
increase when the wavelength of the radiations becomes still
shorter. This correspondence serves as a clear demonstration
that the changes in the protein which are brought about by
the ultraviolet radiation are the same as those which destroy
the bacteria." It seems significant that direct investigation
of irradiated micro-organisms shows that their proteins have
been coagulated.
From what has been said it is clear that all micro-organisms
which have proteins as the main constituent of their proto-
plasm (and we know of no living thing which is devoid of
protein) must be destroyed by the action of ultraviolet light.
As the alteration in the proteins and the associated destruc-
tion of the bacteria proceed even in the absence of water and
oxygen and at very low temperatures, the probability that
viable germs arrived on the Earth from space would seem to
be zero. The light of the stars is rich in ultraviolet radiation.
On the surface of the Earth we are protected from its harm-
ful effects by the atmosphere surrounding us. On escaping
from this atmosphere the germs of life would inevitably be
destroyed by the activity of the ultraviolet radiations which
traverse interstellar space.
It is true that other ' hypotheses ' have been brought
forward of recent years in an attempt to redeem the theory
under discussion. For example, it has been suggested that
life might have been brought here at some time by the
landing of astronauts, that is to say, highly developed con-
PRESENT STATE OF THE PROBLEM 69
scious beings who could undertake interplanetary journeys.
This sort of suggestion is, however, more reminiscent of
science fiction than of a serious scientific hypothesis. The
facts which are at present available to science convince us of
the absolute impossibility of viable germs traxelling to the
Earth through space.
It is interesting to note that, in spite of his ardent belief
in the possibility of interplanetary travel, the outstanding
Russian scientist and inventor K. Tsiolkovskii"''' nevertheless
categorically denied the possibility of this sort of artificial
transport of microbes. When he died in 1919 he left a manu-
script entitled The origin of plants on the terrestrial globe
and their development. In it we may read " My work has
shown that it will be possible to devise means whereby any
living thing may be artificially transmitted from the Earth
to another planet and back safely, but mankind is not
proceeding very fast tovvards the realisation of this possibil-
ity." However, he goes on to say that this form of transport
of life ' with the help of reason ' could not have occurred,
for no traces had been observed suggesting that at any time
or place there have been such highly developed beings
deliberately visiting the Earth. Tsiolkovskii wrote in con-
clusion: " This means that life did not reach the Earth from
the planets even with the help of reason."
Thus we see that the theory of the eternity of life, like
that of spontaneous generation, is in radical contradiction to
the observed facts. While travelling through interstellar
space with nothing to protect them from the lethal radiations,
not only would the germs of life be inevitably destroyed.
but even their internal structure would undergo profound
alteration in a comparatively short time. We must therefore
reject the hypothesis that the germs of life reached the Earth
from somewhere else and must seek the source of life vvithin
the confines of our own planet.
yo ETERNITY OF LIFE
BIBLIOGRAPHY TO CHAPTER II
1. T. GoMPERZ. (See I. 5).
2. A. KiRCHER. Mundus sublerraneus. Amsterdam, 1665.
Quoted by Lippmann (I. 1).
3. W. Thomson (later Lord Kelvin). Presidential Address,
Edinburgh. Rep. Brit. Ass., 1871, ciii.
4. H. V. Helmholtz. Preface to W. Thomson and P. G. Tait :
Handhuch der theoretischen Physik. Braunschweig,
1874.
5. P. VAN TiEGHEM. Traitd de hotanique. (2nd edition), Vol. 1.
Paris, 1890.
6. S. KosTYCHEv. O poyavlenii zhizni na zemle. Berlin (Gosiz-
dat), 1921.
7- (I- 59)-
8. V. I. Vernadskii. Biosfera. Leningrad (Nauchn. khim. tekhn.
Izd.), 1926.
9. V. I. Vernadskii. Problemy biogeokhimii. Vol. 2. Moscow
(Izd. AN SSSR), 1939.
10. V. L Vernadskii. PocJivovedenie, 1^44, (Nos. 4-5), p. 137.
11. Giordano Bruno. Del' infinito universo e mondi. In Opere
iialiane (ed. G. Gentile). Bari, 1907-9.
12. Sir J. Jeans. The universe around us. Cambridge, 1929.
13. E. Holmberg. Medd. Lunds astr. Obs. Ser. II, no. 92 (1938).
14. N. N. Pariiskii. Astr. J., Moscow, 16, 77 (1939).
15. N. Rein and N. N. Pariiskii. Uspekhi astron. Nauk, 2, 137
(1941). A. N. Deich. Priroda, y6, 99 (1944).
16. H. Spencer Jones. Life on other ivorlds. London, 1940.
17. CoMTE E.-J.-F. DE S. G. DE MoNTLivAULT. Conjectures sur la
reunion de la lune a la terre . . . etc. Paris, 1821.
18. H. RicHTER. Schmidts Jb., 126, 243 (1865) ; 148, 57 (1870).
19. M. Wagner. Augsburger allgemeine Zeitung, Beilage, 6, 7
and 8 Oct., 1874. Quoted in (I. 59).
20. H. V. Helmholtz. tJber die Entstehung des Planetensystems.
In Vortrdge und Reden. Braunschweig, 1884.
21. S. Cloez. Quoted by H. von Kliiber. Das Vorkommen der
chemischen Elemente im Kosmos. Leipzig, 1931.
22. D. Mendeleev. Osnovy khimii. Vol. 1, p. 379. Moscow
(Gosizdat), 1927.
23. J. L. Smith. Amer. J. Sci. [ser. 3], //, 388, 433 (1876).
24. S. Meunier. Quoted by P. Becquerel. Astronomie, ^8, 393
(1924)
BIBLIOGRAPHY 71
25. C. B. LiPMAN. Ainer. AIus. Novit., no. p,SS {ic)^2).
26. A. Krishtofo\'ich. Paleobolanika. Moscow and Leningrad
(Gosgeolizdat), 1941.
27. V. I. Vernadskii. Nachalo i vechnost' zhizni. Petrograd (Izd.
' Vremya '), 1922.
28. L. Berg. Byull. Moskov. Obshchestva Ispytatelel Prirody,
52 (5)' P- 15 (1947)-
29. O. Shmidt. Priroda, j, 6 (1946).
30. S. A. Arrhenius. Verldarnas utvexkling. Stockholm, 1906 ;
Das Weltall. Leipzig, 1911 ; Das Schicksal der Plane-
ten. Leipzig, 1911.
31. P. Lebedev. Sobranie sochinenii. Moscow (Izd. Moskov.
Fiz. Obshchestva), 1913.
32. A. Nemilov. Kak poyavilas' na zemle zhizn' ? Leningrad
(Izd. ' Obrazovanie '), 1924.
33. P. Shmidt. Anabioz. Moscow and Leningrad (Izd. AN SSSR),
1955-
34. L. Maquenne. C.R. Acad. Sci., Paris, 755, 208 (1902); 141,
609 (1905)-
35. P. Becquerel. Ann. Sci. nat. {Botanique, 9^ serie), 5, 193
(1907)-
36. R. Pictet. Arch. Sci. phys. nat., ^o, 293 (1893).
37. P. Becquerel. C.R. Acad. Sci., Paris, 148, 1052 (1909) ; 1^0,
1437 (1910).
38. C. B. LiPMAN. Bull. Torrey bot. CI., 64, 537 (1937)-
39. E. Kadisch. Med. Kli^iik, 29, 1074 (1931) ; 30, 1109 (1931).
40. B. J. LuYET. Biodynamica. Vol. 1, no. 29, p. 1 (1937)-
B. J. LuvET and P. M. Gehento. Biodynamica. Vol. 3,
no. 60, p. 33 (1940).
41. V. L. Omeliansky (Omelyanskii). Arch. Sci. biol., St. Peters-
burg, 16, ^55 (191 0-
42. P. Kapterev. Izvest. Akad. Nauk S.S.S.R. (Ser. biol.), 6, 1073
(1936) ; Doklady Akad. Nauk S.S.S.R., 20, 315 (1938).
43. L. Kriss. Mikrobiologiya, p, 789 (1940).
44. Biological effects of radiation (ed. B. M. Duggar). Vols. 1
and 2. New York, 1936.
45. P. Becquerel. C.R. Acad. Sci., Paris, i^i, 86 (1910).
46. J. A. Sanderson and E. O. Hulburt. Radiation biology
(ed. A. Hollaender, et al.). Vol. 2, p. 95. New York,
1955-
47. D. E. Lea. Actions of radiation on living cells. London,
1946. .
72 ETERNITY OF LIFE
48. R. Latarjet, Symposium on Radiobiology, Oberlin College,
19^0, 241 (1952).
M. R. Zelle and A. Hollaender. Radiation biology (ed.
A. Hollaender, et al). Vol. 2, p. 365. New York,
1955-
49. R. Wiesner. Arch.Hyg.,Berl.,6i, 1 (1907).
50. W. S. Moos. /. Bad., 6^, 688 (1952).
51. F. L. Gates. Proc. Soc. exp. Biol., N.Y., 21, 61 (1923); /. gen.
Physiol, 75, 231, 249 (1929).
52. E. Ya. Graevskii. Doklady Akad. Nauk S.S.S.R., 55, 849
(1946).
53. A. D. McLaren. Advanc. EnzymoL, p, 75 (1949)-
54. H. L. Stedman and L. B. Mendel. Amer. J. Physiol., yy, 199
(1926).
55. C. Sonne. Strahlentherapie, 28, 45 (1928).
T. M. Rivers and F. L. Gates. /. exp. Med., 4^, 45 (1928).
56. K. TsiOLKOvsKii. Unpublished MSS (1919).
CHAPTER III
ATTEMPTS AT A SCIENTIFIC APPROACH
TO THE PROBLEM OF THE
ORIGIN OF LIFE
The mechanistic concept of the self-formation
of living things.
As was pointed out in the previous chapters, science, during
the second half of the nineteenth century, was in a critical
situation as concerns the problem of the origin of life. The
old principle of spontaneous generation had been overthrown,
and scientists felt that they had been deprived of the possi-
bility of any experimental approach to the problem of the
origin of life on the Earth. A period of disillusionment and
pessimism set in, which survived from the last years of the
nineteenth century well into the twentieth. Very many
scientists tried somehow to evade the problem, either by
promoting the theory of the eternity of life or by becoming
open idealists and relegating the question from the field of
science to that of faith. Nevertheless, some advanced and
progressive scientists struggled against this kind of attitude
right from the beginning. They felt that their chief task,
amid the surge of idealism, was to defend the principle of
a materialistic approach to the problem of the origin of life.
As an example may be mentioned here the remarkable
statements of T. H. Huxley and J. Tyndall at the meetings
of the British Association held in the i86o's and 1870's.
These meetings served as a forum into which were brought
the great controversies of scientific principle of that period.
In his presidential address to the British Association, Huxley
wrote^ :
If it were given to me to look beyond the abyss of geologically
recorded time to the still more remote period when the earth
was passing through physical and chemical conditions, which it
73
74 A SCIENTIFIC APPROACH
can no more see again than a man can recall his infancy, I
should expect to be a witness of the evolution of living proto-
plasm from not living matter. I should expect to see it appear
under forms of great simplicity, endowed, like existing Fungi,
with the power of determining the formation of new protoplasm
from such matters as ammonium carbonates, oxalates and tar-
trates, alkaline and earthy phosphates, and water, without the
aid of light.
In just the same way Tyndall, in his address of 1874,^
discussed the theory that life originated from lifeless matter.
From that time to the present, there have been unceasing
efforts to find a scientific solution to the problem of the
origin of life, regarding it as an occurrence which could be
interpreted on a materialistic basis. This important and
extremely difficult task has required, and still requires, not
simply an explanation of these wonderful occurrences in
time past but also verification of the correctness of such an
explanation.
For nearly a century now these efforts have proceeded
according to two clearly distinct principles. First, the meta-
physical principle, according to which living things were
suddenly formed under some special conditions, separating
themselves from a lifeless medium in the same way as crystals
separate themselves from their mother liquors. Secondly,
the evolutionary principle, which considers the origin of life
in relation to the general development of matter and sees the
emergence of the first organisms as a definite stage in this
development.
The evolutionary principle, as it relates to our problem,
was first formulated by Lamarck at the beginning of the
nineteenth century. Lamarck's^ well-known theory of the
evolution of organic nature, which was based on the ideas
of the French encyclopaedists,* enjoys a wide and well-
merited popularity. His ideas about the development of life
are, however, less well known. They are to be found in a
work written in 1820 under the title Systeme analytique des
connaissances positives de I'homme restreintes a celles qui
previennent de V observation.^ Here Lamarck described the
origin of living things from lifeless material as a process of
gradual development of matter. On this basis Lamarck
THE MECHANISTIC CONCEPT 75
formed the opinion that " among the inorganic bodies " there
must have developed " extremely small, half-liquid bodies of
a very diffuse consistency ". Then " these small, half-liquid
bodies developed further into cellular bodies having an outer
envelope with liquid contained in it and acquiring the first
rudiments of organisation . . ."
There was also a broad development of dialectical methods
of thought in classical German Naturphilosophie at the
beginning of the nineteenth century. Although, as we have
seen in Chapter I, most of the representatives of this school of
thought supported the theory of spontaneous generation, we
find in the works of L. Oken*^ a fairly well ^vorked out form
of the idea of the gradual evolution of carbon compounds,
leading up to the formation of the primaeval slime from
which all living things later developed.
In his works Charles Darwin hardly ever made direct
reference to the development of the first living things which
were to become the first ancestors of everything living on the
Earth. It was only in one of his letters to Wallace (written
in 1872), in which he was criticising Bastian's experiments
and considering them to be completely unconvincing, that
he stated that spontaneous generation was quite unproven.
Nevertheless he continued, ' On the whole it seems to me
probable that Archebiosis is true.* I should like to live to
see Archebiosis proved true, for it would be a discovery of
transcendent importance.' In Darwin's opinion life must
have arisen sometime and somehow but we are still com-
pletely unaware of the manner in which this took place. '^
However, these isolated utterances of Darwin are not so
important for the solution of our problem as the fact that
he applied evolutionary principles to explain the develop-
ment of higher organisms from lower ones and showed that
it was impossible to conceive of living things coming into
being without evolutionary development.* Mechanistic con-
cepts of the essential nature of life were, however, still so
firmly entrenched in the minds of the scientists of the second
* " Perhaps the words archebiosis. or archegenesis, should be reserved for
the theory that protoplasm in the remote past has developed from non-
living matter by a series of steps. ..." Encyclopaedia Britannica, Vol. 1.
p. 48. London, 1956. — Translator.
76 A SCIENTIFIC APPROACH
half of the nineteenth century that they overrode the prin-
ciple of evolution in relation to the problem of the origin
of life, although a great deal of preparatory work had already
been carried out along evolutionary lines.
The mechanistic conception of life and its origin prevalent
in those times was fundamentally this: there is no essential
difference between organisms and inorganic bodies. Living
things are merely special forms of machines having an
exceptionally complicated structure of integrated material
particles. Just as the specific function of a machine is deter-
mined by the particular circumstances and arrangements of
its parts, so the life of an organism depends on the finest
details of its internal structure, on the proper interrelation
between the atoms and molecules in living protoplasm.
From this it follows that the emergence of life is not the
emergence of something qualitatively new. The whole ques-
tion simply comes to this: how did the combinations of
material particles characteristic of life arise and how did
the peculiar structure of all living things arise?
In the inorganic world we are constantly observing the
formation of structures built in an orderly way under the
action of definite physical forces ; crystals develop from
molecules or ions scattered at random throughout the solu-
tion. According to the mechanists the problem of the origin
of living things is, in the last analysis, nothing but the problem
of the crystallisation of organic matter. Thus the primary
origin of life seems to be a logically inevitable deduction
from the theory already propounded.
In practice, however, the facts prove to be in direct contra-
diction to this hypothesis. Nowhere in nature do we observe
the primary origin of life and all our attempts to reproduce
this phenomenon under artificial conditions have been fruit-
less.
The only way which the mechanistically minded scientists
of those times could see out of the blind alley which they
had thus created was to suppose that the conditions for the
formation of living structures, ' the crystallisation of living
matter ', were so complicated and specific that this crystallisa-
tion could only take place in the remote past and is now
impossible because the physical or chemical conditions on
HAECKEL AND PFLUGER 77
the Earth are no longer appropriate. This idea was formu-
lated with special precision during the second half of last
century by the distinguished German scientist E. Haeckel
in his theory of archegony.^
The views of Haeckel and Pfliiger.
Haeckel was a convinced and militant supporter of the
so-called monistic concept of the world which denied that
there was any essential difference between organisms and
inorganic bodies. "All natural bodies with which we are
acquainted on the Earth," he wrote, " both the animate and
the inanimate, are similar to one another in all the essential
properties of matter. Life is already present in the atom."
Thus, although the primary origin of living things had still
not been demonstrated by direct experiment it nevertheless
seemed indubitable, ' the logical postulate of natural philo-
sophy '.
The hypothesis that the germs of life travelled through
interplanetary space cannot explain the appearance of life
on the Earth. However, as there was a time when the Earth
was in such a state that living things could not possibly
have inhabited it, organisms must have arisen from inert
matter at some time since this stage of the development of
the Earth. This is not inconsistent with the fact that we
cannot, at present, observe the spontaneous generation of
microbes. The development of organisms from lifeless matter
was perfectly possible at remote periods in the existence
of our planet, because special conditions prevailed then
which were different from the conditions obtaining now.
According to Haeckel it would seem that the primaeval
organisms must have been completely homogeneous, struc-
tureless, formless lumps of protein. They developed directly
bv the simple interaction of solutions in the primaeval sea
of matter.^"
Haeckel did not explain how this development took place.
He even took the view that
any detailed hypothesis whatever concerning the origin of
life must, as yet, be considered worthless, because, up till now,
we have not any satisfactory information concerning the ex-
78 A SCIENTIFIC APPROACH
tremely peculiar conditions which prevailed on the surface of
the earth at the time when the first organisms developed.
Thus Haeckel believed that the most primitive organisms
must have arisen spontaneously from inorganic matter as
a result of the formative action of some special external
physical forces. This does not occur now because those
forces which were present on the Earth at an earlier stage
in its development have now disappeared and cannot be
reproduced.
Haeckel's contemporary W. Preyer^^ laughed rather malici-
ously at these life-forming forces and the conditions which
Haeckel supposed to be necessary for the emergence of life
in remote geological epochs. He declared that one could
not conceive what these conditions might have been. If they
were the same as those now prevailing, it would seem that
the emergence of life was impossible because, as Pasteur's
work showed, this emergence does not occur at present. If
the conditions were substantially different the organisms
which had emerged would quickly have been destroyed
because they only exist at present under very narrowly cir-
cumscribed external conditions.
These ideas of Preyer's seem quite convincing if one adopts
a mechanistic position and assumes the sudden emergence
of organisms which, though far simpler, already possessed
all the organisational characteristics which we find in con-
temporary living things.
Such objections, however, take on a different aspect if we
discard mechanistic principles and adopt the point of view
that the primaeval living things arose by stages as the result
of a prolonged evolution of organic substances, as a particu-
lar stage in the general historical development of matter.
In this case we shall not need to invent any special forces or
conditions. If it had been accomplished by a process of evolu-
tion of organic substances, the emergence of the primaeval
living things could have occurred under approximately the
conditions of temperature, moisture, pressure, illumination,
etc., which now prevail on the surface of the Earth.
There was one condition, necessary for this evolution,
which was present then on the surface of the Earth and is
HAECKEL AND PFLUGER 79
not present now, and that, though it may at first glance seem
paradoxical, was the absence of life. Only in the absence
of organisms could life develop. Organic substances arising
on the surface of the Earth at present w^ould not be able to
undergo prolonged evolution. After a comparatively short
time they would be annihilated, devoured by the multitude
of organisms, well equipped for the struggle for existence,
which inhabit all parts of the earth, w^ater and air. On the
other hand, in the remote past when our planet was still
sterile, the process of evolution of organic substances could
be prolonged indefinitely and this could have led up to the
emergence of the primaeval living things in accordance with
certain natural laws which we shall discuss later.
This idea, as we now know, was already clear to Darwin,
who -^vrote in a letter dated 1871 as follows:
It is often said that all the conditions for the first production
of a living organism are 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 com-
pound was chemically formed ready to undergo still more com-
plex 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. ^^
Nevertheless, at the end of last century and the begin-
ning of the present one, the mechanistic concept of the self-
formation of life under the influence of some elementary
physical forces and effects still prevailed extensively in the
minds of scientists. Many of them were so carried away
as to make assumptions concerning the nature of these forces
and to draw a picture of the emergence of living things from
inorganic matter under the circumstances obtaining on the
primaeval Earth. Among these forces were included elec-
trical discharges, ultraviolet radiations, the forces of chemical
affinity and later even the radioactivity of the elements. As
we shall see later, all these factors must certainly have played
an important part as sources of energy in the transformation
of organic substances in the process of their evolution on
the primaeval Earth. However, in themselves they certainly
8o A SCIENTIFIC APPROACH
could not have brought about the spontaneous generation
of organisms in the remote past any more than they can
to-day. For this reason all such hypotheses sounded extremely
unconvincing and not a single one of them served as a basis
for further fruitful investigations.
We may here cite, by way of illustration, only a few of
the many investigations referred to above. F. J. Allen^^ dated
the emergence of life at the time when water already formed
the primitive ocean on the surface of the Earth. At that time
the heavy, stable, insoluble compounds were laid down in
the crust of the Earth while the less stable ones, in process
of decomposition, were present in gaseous form in the atmo-
sphere and in solution in the water. Nitrogen, oxygen and
carbon dioxide were present in the water and atmosphere.
In the presence of electric discharges occurring as flashes
of lightning incessantly passing through the warm, moist
atmosphere, ammonia and oxides of nitrogen were formed
and dissolved in the rain which carried them down into the
water. Here they encountered dissolved carbon dioxide,
chlorides, sulphates, alkali phosphates and other metallic
salts. It was then possible for the compounds of nitrogen,
to which Allen attached special importance, to enter into
reactions with various other substances. On their combina-
tion with carbon dioxide oxygen was liberated and the first
living substance was formed and already exhibited essen-
tially the same properties which we find in organisms at the
present day.
Allen did not go into much detail about the formation of
living matter. He only made the suggestion that, in the
transfer of oxygen from or to nitrogen, sunlight might have
played a significant part when it was absorbed by iron com-
pounds dissolved or suspended in the water. Taking a general
view of all these hypotheses it is impossible to conceive how
the forces invoked by Allen could give rise to organised
matter.
Similar hypotheses were developed somewhat later by H. F.
Osborn. At the beginning of his book. The origin and
evolution of life,^^ he describes the Earth before life was
present on it, closely wrapped, as by a blanket, by the atmo-
sphere of that time which contained large amounts of water
HAECKEL AND PFLUGER 8l
vapour and carbon dioxide. Osborn thought that this carbon
dioxide acted as the source of carbon for the formation of
those organic compounds from which living organisms later
de\'eloped. He wTote :
We may advance the hypothesis that an early step in the
organization of living matter was the assemblage, one by one,
of several of the ten elements now essential to life ... Of these
the four most important elements were obtained from their
previous combination in water (HoO), from the nitrogen com-
pounds of volcanic emanations or from the atmosphere consist-
ing largely of nitrogen, and from atmospheric carbon dioxide.
However, Osborn did not give any explanation of the way
in which this sort of transformation came about. He confined
himself to rather vague statements about the ' attractive
force ' of oxygen and hydrogen.
Similar views w^ere developed by W. Francis,^^ who
attached far greater significance to iron in the process of the
formation of life, and by many other authors in the first
quarter of this century. It is characteristic of most of these
authors that they were convinced that living things developed
directly from lifeless matter as a restdt of the formative
activity of some external force.
The practical outcome of all these hypotheses was the
carrying out of experiments in which the forces which were
supposed to have given rise to life in the past ^vere repro-
duced in the present under laboratory conditions. However,
as was to be expected, these experiments did not meet with
success and are now completely forgotten. Only a few of the
more typical investigations w411 be discussed here.
R. Dubois^® placed pieces of radium or barium chlorides
on the surface of a sterile gelatin broth, and, according to
his o^vn account, he obtained microscopic granulations
resembling colonies of microbes. They moved actively, giew^
and divided but cotdd not be subcultured on sterile portions
of the broth.
Similar experiments were ptiblished somewhat later by
M. Kuckuck^^ under the grandiose title Losung des Problems
der Urzeugung. According to the observations of this author,
when radium acted on a mixture of gelatin, glycerine and
6
82 A SCIENTIFIC APPROACH
common salt for 24 hours a peculiar culture grew, living
cells were formed which grew, divided and manifested other
features characteristic of life. This work was obviously very
amateurish and is certainly of no real importance. It cannot,
however, be regarded as an accidental happening or a mere
curiosity. It could only have been done under the influence
of the mechanistic outlook which we have already discussed.
According to this view, the simplest living things could
suddenly crystallise out from lifeless matter. The only
requirements for this were various more or less specific
unknown forces which effected this sort of transformation of
substances into living things. M. Kuckuck attributed such
effects to radioactive phenomena, which were still poorly
understood at that time.
Another well-known German scientist of the end of last
century, E. Pfluger,^* approached the subject under discus-
sion in a different way from Haeckel. He sought the cause
of the emergence of life in the materials from which the
organisms were to emerge as well as in the peculiarities of
the external conditions. In his analysis of the problem he
started out from the properties of the chemical substance
protein, a substance which he associated inextricably with
the existence of living processes. Pfliiger considered that
there are present in organisms two radically different cate-
gories of protein, the reserve protein which was ' dead ' and
the protein of the protoplasm which was ' living '. In the
former category he included such substances as the whites
of eggs and the protein stores of seeds, etc. These proteins
appeared to be very stable, chemically inert substances. In
the absence of micro-organisms they may be preserved for
an indefinitely long time without undergoing any important
changes. The ' living ' protein of the protoplasm, on the
other hand, seems to be very unstable. Pfliiger held that this
instability formed the basis for the chemical transformations
which proceed within the living cell.
In all living things disintegration of proteins takes place.
Pflriger attributed this to various special chemical groups
in the composition of ' living ' protein. In particular, he
thought that ' living ' protein must have the power to oxidise
itself by using the oxygen of the air. This follows from the
HAECKELANDPFLUGER 83
fact that, when living substances decompose spontaneously,
carbon dioxide is always formed, whereas carbon dioxide
cannot be formed by direct oxidation of the carbon atoms of
proteins. The products obtained by the decomposition of
' dead ' proteins and even ' dead ' proteins themselves are
quite incapable of this sort of oxidation. Consequently there
must be present in ' living ' proteins some special atomic
grotipings or radicals which can break themselves down and
oxidise themselves.
Pfliiger considered that cyanogen represented such a radi-
cal in the molecule of ' living ' protein. He considered this
to be thoroughly demonstrated by a comparison between the
nitrogen-containing products of the decomposition of protein
obtained as a result of the normal metabolism of living organ-
isms with the corresponding products of the decomposition
of ' dead ' protein which are formed when it is broken down
artificially. There is a radical difference between such pro-
ducts. The products which are characteristic of the break-
down of ' living ' protein in the organism such as urea, uric
acid, etc., are never obtained from the artificial breakdown
of ' dead ' protein. Ho'^vever, these characteristic substances
can easily be produced from compounds containing cyanogen
groups by rearrangement of the elements, as occurred in
the synthesis of urea from ammonitim cyanate by Wohler.
Pfliiger thus tried to relate the whole metabolism and all
the properties of living protoplasm to the presence of definite
chemical groupings, the cyanogen radicals, entering into the
composition of ' living ' proteins.
Contemporary biochemistry has long ago disproved these
hypotheses of Pfliiger. It has not succeeded in discovering
any specific cyanogen-containing radicals which differentiate
' living ' from ' dead ' protein, and even the separation of
proteins into these two categories is now considered to be
without any real justification. In particular, it has now been
shown that the so-called reserve proteins of the seeds of
plants have an enzymic activity similar to that of the proteins
of protoplasm." The end products of nitrogen metabolism
in animals, urea and uric acid, arise as a result of secondary
synthesis and not by direct oxidation of cyanogen-containing
radicals in the molecules of the ' living ' protein. It is now
84 A SCIENTIFIC APPROACH
quite obvious to us that Pfliiger oversimplified the compli-
cated phenomenon of the metabolism of living protein. It
is, however, of interest in connection with the problem we
are studying, that Pfliiger built up his original theory of the
origin of life on this basis. If the cause of all vital phenomena
lies in special groups of atoms, the cyanogen-containing
radicals of proteins, then, he argued, it is clear that the
whole solution of the problem of the origin of life resolves
itself simply into a solution of the question of how these
radicals arose. How was cyanogen formed on the primaeval
lifeless Earth? Pfliiger wrote :
In this connection organic chemistry provided us with a very
significant fact, namely that cyanogen and its compounds are
formed at incandescent temperatures when the necessary nitro-
gen-containing compounds are brought into contact with glowing
carbon or when mixtures of the substances are raised to white
heat. Thus nothing could be clearer than the possibility that
cyanogen compounds might be formed at a time when the earth
was partly or wholly in a fiery or incandescent state. Life arose
from fire and its foundations were laid at the time when the
earth was a fiery incandescent globe.
This theory was very progressive for its time and played
a positive part in the history of the development of our
ideas concerning the origin of life in so far as it included
an attempt to explain the primary development of organic
substances. However, the hypothesis on which it was based,
namely that the vital characteristics of protoplasm could be
attributed to the presence of cyanogen or some other radicals
in the composition of the proteins, was found to be false and
was later refuted.
It must be noted that at the end of last century and
the beginning of the present one opinions, which were very
widely held, associated life and all its properties, not with
protoplasm in its entirety but with particular hypothetical
' living molecules ' or molecular complexes the chemical
reality of which was far more problematical than that of the
cyanogen-containing radicals of Pfliiger's ' living protein '.
The biological literature of those times is very rich in
different complicated names which were thought out to
HAECKEL AND PFLUGER 85
designate the purely speculative, primary structural units of
living substances, ' the idioplasm ' of Naegeli and Weismann,
' the biogenes ' of Verworn, ' the plastomes ' of Wiesner, ' the
protomeres ' of Heidenhain, ' the gliodes ' of Botazzi, ' the
vitules ' of Meyer, * the vitaids ' of Lepeschkin, ' the mole-
culobionts ' of Alexander and Bridges, etc., etc.
Naturally such authors tried to solve the problem of the
origin of these hypothetical units of life, substituting this for
a solution of the problem of the origin of life itself. That,
however, did not carry them any further forwards, as the
one problem presented no less difficulty than the other.
As early as the end of the nineteenth century A. Weis-
mann^"'^^ put forward his theory that every organism contains
a special germinal substance which does not change in the
course of life (' idioplasm '). In particular, this is regarded
as carrying the hereditary endowment and other character-
istics of the organism. All the rest of the body of the organism
(' soma ') is merely a lifeless receptacle, a nutrient medium
for the germinal substance in which alone life is inherent.
The germinal plasm, as Weismann puts it, " never arises
anew but grows and reproduces itself uninterruptedly ".
Natural philosophy poses the question: How, then, did
this substance arise in the first place? Weismann himself
only gave a very general and rather vague answer. He stated
that in the beginning, under special conditions which are
quite unknown to us, there must first have arisen very small
living entities, ' biophores ', which themselves represented the
fundamental active elements of the germ plasm."
This idea of Weismann's was reflected in a number of
later pronouncements. In particular, we may take as an
example the * theory of symbiogenesis ' of C. Mereschkow-
sky," which made a great sensation in its time. According
to this theory there are two types of plasm which are not
only radically different from one another in their properties,
but even have a different historical origin. The first type,
that called ' mycoplasm ', was essentially the same as the
chromatin of the nucleus. The second type — called ' amoebo-
plasm ' — was simply what we now call cytoplasm. The very
earliest forms of life, which were formed spontaneously at a
time when there were still no organic substances and when
86 A SCIENTIFIC APPROACH
the original water on the surface of the Earth was near to
boiling point, were, according to Mereschkowsky, ' biococci ',
minute ultramicroscopic particles of ' mycoplasm '. They
were completely structureless but were already able to syn-
thesise proteins and carbohydrates directly from inorganic
substances. The first things to be formed from these ' bio-
cocci ' were bacteria.
Later, when the temperature of the water on the Earth
had fallen below 50° C and an abundance of organic nutrients
had appeared in it as a result of the vital activity of the
biococci, there were formed small masses of ' amoeboplasm '
which crawled along the bottom of the ocean and devoured
the bacteria. The cells with nuclei which we now meet arose
as a result of the symbiosis of these two different types of
organism when the biococci which had entered the amoebo-
plasm were not digested but manifested their capacity for
symbiosis.
The characteristic feature of this fantastic theoiy of the
emergence of life is that it laid special emphasis on the
essential difference between the cytoplasm and the nucleus,
giving the first importance to the independent origin of the
latter.
Similar ideas were propounded by the well-known English
biologist E. Minchin. According to Minchin,^* the first living
things were minute, ultramicroscopic particles of chromatin.
These particles were endowed with the ability to metabolise
substances independently and, in particular, to synthesise
organic compounds from simpler inorganic salts. It was only
later that the protoplasm enveloping them was formed and
this, in the last analysis, only acted as a medium for their
existence.
We have dwelt in some detail on these hypotheses because
they have been reflected to some extent in the views concern-
ing the emergence of life which are now held in certain
circles.
Attempts to construct ' models of
living organisms'.
Attempts to solve the problem of the origin of life by
producing so-called ' models of living bodies ' were crudely
'models of living organisms' 87
mechanistic in character. These attempts were made at the
beginning of the present century because many biologists
of that time considered that the cause of the vital properties
of protoplasm resided only in its structure, that is, in its
specific spatial configuration, while completely ignoring the
metabolism, that form of the motion of matter which is
characteristic of life.
At that time they conceived the spatial organisation of
protoplasm in terms of a machine ; a definite construction
formed from some sort of solid and unchanging interrelated
' beams and braces '. From this point of view the structure
of protoplasm with the rigidly determined spatial arrange-
ment of its parts was the specific cause of life in the same
way as the disposition of the wheels, beams, pistons and other
component parts of the mechanism determine the particular
function of a machine.
L. Jost^^ wrote as follows :
The functioning of a machine does not depend primarily on
the chemical properties of its components but on their arrange-
ment and interrelationship. We may construct a machine of
brass or of steel and this will certainly affect its durability and
accuracy but will not affect the nature of the work it does.
Similarly, Jost held, the activity of living cells depends
more on the arrangement of their parts than on the composi-
tion of the protoplasm. It follows that the direct route to
the understanding of life is not through the study of the
metabolism and other vital phenomena but through the
investigation of the structure of protoplasm and the spatial
arrangement of its parts.
The next stage in the historical development of the subject
lay in the attempt to see directly, through the microscope,
the spatial configuration which formed the basis of life, and
the belief that this attempt was only unsuccessful because of
the insufficiency of our optical methods. If we could see the
finest details of the structure of protoplasm we should thus
understand life itself. The actual working out of this prin-
ciple, however, only led to bitter disappointments. The
simple observation of living cells under the microscope gave
very little indication of a machine-like structure of proto-
88 A SCIENTIFIC APPROACH
plasm. More refined methods of investigation came into use.
Before it was examined under the microscope the protoplasm
was killed or fixed, and then stained. These methods opened
up a whole new world of structures and reawakened the hope
of visualising the construction of the mechanism of life.
The filamentous, reticular and alveolar theories of the struc-
ture of protoplasm followed one another very quickly. By
the beginning of the twentieth century, however, it had
been shown that all the fine structures which could be seen
in fixed preparations were artefacts arising after the death
of the cell as a result of reactions between the fixative and
the proteins of the protoplasm.^® It became quite clear that
a study of these structures gives us very little understanding
of the organisation of living substance. ^^
At about this time and arising out of such theoretical con-
siderations, some attempts were made to study life by means
of artificially produced living structures, by the construction
of models of living protoplasm. Even before this M. Traube-^
had immersed small crystals of potassium ferricyanide in an
aqueous solution of copper sulphate and obtained globules
surrounded by fine membranes of copper ferricyanide. Under
the influence of osmotic pressure these globules grew and,
to a certain extent, reproduced the phenomena of the growth
of living cells.
O. BiAtschli^® later made a model which reproduced the
movements of a living amoeba. He used drops of olive oil
mixed with a solution of potash. As a result of changes in
surface tension these drops threw out pseudopodia like
amoebae and moved towards solid particles and even en-
gulfed them just as amoebae engulf particles of food. Similar
very simple models simulating the movement, feeding and
division of cells were also produced by L. Rhumbler^" and
a number of other workers.
These models had a certain scientific interest only insofar
as the phenomena which occurred in them were based on
the same physico-chemical causes as those operating in the
living cell. Such models enabled the experimenters to study
the phenomenon in question in greater detail under circum-
stances which were simpler than those occurring in proto-
plasm. This, however, was not what most of these workers
'models of living organisms' 89
were aiming at when they constructed their models. They
argued that once the essence of life was shown to be associated
with a particular structure, it was only necessary to reproduce
that structure, albeit with materials unlike those of the organ-
ism, to obtain a system endowed with life — a ' living model '.
Many people were specially attracted to the artificial
reproduction of various structures at that particular time
because they were looking for some sort of material frame-
work or mechanical structure in protoplasm which would
determine all the vital phenomena. It was natural, therefore,
to wish to create analogous structures artificially. By mixing
and precipitating various substances numerous authors did
indeed succeed, on many occasions, in obtaining a micro-
scopic picture which strikingly resembled those structures
which may be observed in fixed and stained preparations of
plant and animal tissues.
Delighted by the superficial resemblance, these authors
enthusiastically proclaimed that they had reproduced living
protoplasm artificially. But this was far from being so. Not
only were the artificial models lifeless, but even the struc-
tures resembling them in the fixed cells were dead. As
we have already mentioned, the filamentous, reticular and
alveolar structures are artefacts which develop after the death
of the cell, as a result of reactions between the proteins and
those substances which are used for the fixation and staining
of the preparation. The appearance of similar structures in
the experiments with models is quite understandable, for
here too there takes place just such a precipitation of mixed
colloids as occurs during the fixation of protoplasm. This,
however, contributes very little to our understanding of life.
Scientific interest in this sort of artifical structure, therefore,
declined very quickly.
Nevertheless, in a few scattered laboratories, people con-
tinued for a long time to try to ' synthesise life ' by the
construction of analogous structural forms. As an example
we may cite the experiments of S. Leduc^^ in which he pro-
duced so-called ' osmotic cells '. Leduc produced just the
same sort of phenomena as Traube but under far more com-
plicated conditions. He used small pieces of melted calcium
chloride and immersed them in saturated solutions of potash
go A SCIENTIFIC APPROACH
or tripotassium phosphate. Semipermeable membranes of
calcium carbonate or calcium phosphate were thus produced
and these formed osmotic globules (Figs. 6 and 7).
Leduc considered that his experiments might form the
basis for a new trend in biology. He called this ' synthetic
biology ' : the science of obtaining living forms from lifeless
materials in the laboratory. He set out not so much to eluci-
date the physical forces underlying the phenomena which
were produced, as to attempt to endow his models with a
greater superficial resemblance to living organisms by the
use of very complicated procedures, some no more than hocus
pocus. Certainly his ' osmotic fungi and algae ' looked
remarkably like the corresponding living objects. But how
does this really help us to understand life?
The resemblance between the objects created by Leduc
and living things was no greater than the resemblance
between a living person and a marble statue of him, and
nobody ever set much store by the animation of Galatea or
the visit of the ' Stone Guest '.*
The work emanating from the laboratory of the Mexican
investigator A. L. Herrera^^ was of the same nature. In the
preparation of his structures, this author used somewhat
different materials from those used by Leduc. He mixed
solutions of thiocyanates with solutions of formalin. This
led to the formation of nitrogen-containing substances of
high molecular w^eight giving colloidal solutions. When
these were fixed with formalin or alcohol, precipitation took
place and quite complicated structures were formed. In the
course of many decades Herrera made thousands of prepara-
tions of these structures, some of which showed a remarkable
resemblance to those formed on the fixation of cells. (I have
been able to satisfy myself personally that this is so by examin-
ing preparations sent to me by the author.) Herrera also
described his experiments in bulletins specially published
by him in which he also gave numerous sketches of the
structures which he obtained (Fig. 8).^^
The interest of these studies lies in the fact that they
demonstrate what different forms colloidal substances can
* The reference is to A. S. Pushkin's work of this name: cf. II Commendatore
in the opera Don Giovanni — Author,
Fu;. 6. Leduc's arlifu ial al'-ac.
Fig. 7. Leduc's artificial funoi.
MODELS OF LIVING ORGANISMS
91
assume according to the method of their preparation. These
experiments can. however, hardly be regarded as ' plasmo-
geny ' — a means of obtaining living organisms artificially.
Herrera, however, took just this view in 1942 when he
published his New theory of the origin and nature of life.^*
Fig. 8. Herrera's artificial cells.
He based it on his experiments on the structures made out
of thiocyanates. Such structures can certainly arise, as
Herrera asserts, under natural conditions, but it is doubtful
w^hether any contemporary biologist would admit that these
structures are endowed with life. These structures have no
organised metabolism and cannot reproduce themselves. The
single fact of their resemblance to the structures seen in fixed
tissues cannot alone serve as a criterion of life.
92 A SCIENTIFIC APPROACH
The ideas which we have been discussing are understand-
able up to a point because a very negative attitude towards
the problem of the origin of life prevailed in the biological
literature of the twenties and thirties of this century. It was
treated as a problem upon which it was not worth while for
any serious investigator to waste his time.
The evolutionary theory of the origin of life.
In spite of the widespread prevalence of mechanistic
opinions at the beginning of the twentieth century, the
evolutionary approach to the problem of the origin of life
was not entirely abandoned. As we have already pointed out,
the great minds of the nineteenth century favoured this
approach to the problem.
As early as the 1870s F. Engels indicated that the evolu-
tionary development of matter was the only path by which
life could have arisen. According to Engels, life does not
arise arbitrarily and is not eternal. It arises by a process
of evolution of matter whenever conditions are favourable."
These profoundly significant ideas of Engels were, how-
ever, not widely enough reflected in the work of the experi-
mental scientists of those times. Only a very few of them
publicly supported an evolutionary solution of the problem
of the origin of life. As an example we may point to an
address given by V. Belyaev in 1893 in the University of
Warsaw. In it this distinguished Russian botanist and cytolo-
gist sketched, though still in rather general terms, the gradual
development of matter which was achieved " in the great
laboratory of nature " on the way to the development of life.
In this connection he pointed out that " We are hardly likely
to succeed in obtaining quickly that on which nature has
spent thousands of years. "^®
An address delivered by E. A. Schafer" at the annual
meeting of the British Association in Dundee was of great
importance in the history of the problem under discussion.
In dealing with the question of the origin of life Schafer
said :
We are not only justified in believing, but are compelled to
believe that living matter must have owed its origin to causes
EVOLUTIONARY THEORIES 93
similar in character to those which have been instrumental in
producing all other forms of matter in the universe ; in other
words, to a process of gradual evolution. . . .
Looking, therefore, at the evolution of living matter by the
light which is shed upon it by the study of the evolution of
matter in general, we are led to regard it as having been pro-
duced, not by a sudden alteration, whether exerted by a natural
or supernatural agency, but by a gradual process of change from
material which was lifeless, through material on the borderland
between the inanimate and the animate to material which has
all the characteristics to which we attach the term ' life '.
The actual process of evolution of organic matter was still
only rather roughly sketched by Schiifer. He spoke, though
very vaguely, of the formation of organic substances and
then of the development of masses of colloidal slime which
possessed the power of assimilation. He then spoke of the
differentiation of certain phosphorus-rich parts of the living
matter, then of the development of enzymes and finally of the
differentiation of the nucleus of the cell. Schafer considered
that any more detailed hypothesis as to the direction and
causes of this evolution was unwarrantable in the light of
the facts known at that time.
K. Timiryazev^* thought very highly of these statements
by Schafer. In his article From the scientific chronicle of
1^12 he reviewed Schafer's address in detail and wrote:
We are forced to believe that living matter, like all other
material phenomena, was brought into being by evolution. The
evolutionary theory now embraces not only biology but all the
other natural sciences, astronomy, geology, chemistry and physics.
It convinces us that the transition from the inorganic to the
organic world was also accomplished by a process of evolution.
More than ten years had passed since Schafer gave his
address when an article on the origin of life on the Earth
by P. BecquereP' appeared in a French astronomical journal.
The chief interest in this paper lay in the devastating criti-
cism to which its author submitted the theory of panspermia.
On the basis of his own experiments he demonstrated most
convincingly the impossibility that living things could have
reached the Earth from interstellar space. In place of this
94 A SCIENTIFIC APPROACH
theory he produced one of his own. " On planets like the
Earth there must always occur at some stage in their evolu-
tion the origin, development and disappearance of life, just
as there is always a beginning, transformation and dissolution
of worlds, and this continues throughout eternity." Terres-
trial life is but a particular instance of this cosmic evolution
of matter. However, Becquerel, like Schafer, only gave a
very rough sketch of the actual evolution of organic matter
leading up to the origin of living organisms.
Like many of his predecessors, Becquerel considered that
carbon dioxide ^vas the first carbon compound existing on
the Earth. He based his theory, which he called ' radiobio-
genesis ', on the experiments of Berthelot and Stoklasa on
the synthesis of organic substances from carbon dioxide by
the action of ultraviolet and radioactive radiations. Accord-
ing to this theory, organic substances arose directly from
carbon dioxide, water and minerals under the influence of
the ultraviolet radiation of the Sun and the radioactivity
of the rocks at some particular geological period. Some truly
colloidal systems were later built up and the germs of life
developed from these.
In these hypotheses Becquerel reverts to the possibility
which he had explained, that organic substances may develop
under the influence of ultraviolet light. However, as con-
cerns the cause of the evolutionary formation of the first
living things, which is the most important and interesting
point to us, his theory still leaves us in the dark, as the author
himself admitted.
In the same year as Becquerel's article appeared, my own
little book The origin of life^^ was published. In it I ex-
pounded for the first time, though still very schematically,
the views which the reader will find more fully worked out
in the present edition. In particular, I tried to show in it
how the simplest carbon compounds, the hydrocarbons, might
have been formed on our planet. The evolution of these
compounds was held to lead to the formation of protein-like
compounds and then colloidal systems which were able to
undergo gradual differentiation of their internal organisa-
tion as the result of natural selection.
Somewhat later, in 1929, J. B. S. Haldane published an
EVOLUTIONARY THEORIES 95
article"*^ which was very significant in the development of
the study of the origin of Hfe. This author also showed that
the development of organic compounds took place before
the formation of the first living things and took an evolution-
ary view of this process.
Afterw^ards, when it was found that the atmosphere of
the large planets contained hydrocarbons which can only
have been formed there abiogenically,*^ the hypothesis that
organic compounds were formed similarly on the Earth
became generally accepted. It must not be supposed, how-
ever, that this meant a complete victory for the evolutionary
over the metaphysical school of thought in relation to the
problem of the origin of life. On the contrary, very many
workers on the problem in the thirties and even the forties
of this century only applied the evolutionary principle to
the origin and development of organic substances. They only
accepted organic chemical evolution. They discussed the
most important event — the transition from the lifeless to
the living state — from a fundamentally metaphysical stand-
point, regarding it as the sudden appearance of ' living mole-
cules ', particles of viruses or genes, which were endowed
with all the attributes of life from their very formation.
This approach to the solution of the problem of the origin
of life was basically that which is associated with the works
of T. H. Morgan^^ and his followers, on the ' genie ' nature
of life.
According to Morgan the first organic things which showed
signs of life w^ere genes. In his paper The gene as the basis
of life H. J. MuUer** described this basis as a particle of
matter endowed with a definite chemical structure, a giant
molecule w^hich is so chemically stable that it has retained
its internal, life-determining structure essentially unchanged
throughout the whole development of life on the Earth from
times ' before green slime bordered the seas ' right up to
the present. According to Muller, life did not arise before
the gene. The first things which were able to grow, from
which arose a substance like that which exists at present,
probably consisted almost exclusively of the gene or genes
already mentioned. Thus, genes formed the basis of the first
living things.
96 A SCIENTIFIC APPROACH
If this is SO, the only thing which is required for a solution
of the problem of the origin of life is an explanation of the
way in which the primary formation of the ' gene molecules '
took place.
The followers of Morgan gave what appeared, at first
glance, to be a very simple answer to this question. The
specific life-determining structure of the original ' gene mole-
cule ' arose purely by chance, simply as the result of a ' happy
conjunction ' of the atomic groups and molecules distributed
in solution through the primaeval w^aters of the oceans.
"... The origin of life is identified with the origin of this
material [genes] by chance chemical combination " wrote
Muller*^ in 1947.
Many authors of papers and books on the question of the
origin of life published ten to twenty years ago proceeded
from this same assumption.
To some extent the conception persists even now. We shall
only consider a few examples of this attitude.
As early as 1924 C. B. Lipman"*^ developed the idea of the
primary formation of ' a living molecule '. He considered
that carbon dioxide, water and nitrates entered into thou-
sands of different combinations with one another in the
primitive watery envelope of the Earth as a result of the
considerable chemical and electrical activity which existed
there. Many different organic molecules of the nature of
amino acids and polypeptides were thus formed. The pro-
perties of these molecules were determined by the spatial
relationships of the atoms. By chance there might even have
arisen a molecule of this sort which, owing to a peculiarity
of its structure, could multiply like a filterable virus. In its
growth and reactions to its environment it might, according
to Lipman, be regarded as ' our first living molecule '. Under
certain circumstances such a molecule would react with other
molecules and would gradually form more and more compli-
cated aggregates until it developed into protoplasm as it
exists at present.
In an article published in 1928, J. Alexander and C.
Bridges*^ also wrote about the chance formation of the first
molecules of living substances — ' moleculobionts ' — which
had laid the foundations for the origin of life on the Earth.
EVOLUTIONARY THEORIES 97
Alexander later*^ gave greater precision to this idea by saying
" that life originated by the chance transformation of an auto-
catalytic unit of molectilar dimensions, for the smaller its
size, the greater the probability of its formation ".
R. Beutner wTote a number of separate papers*' on the
problem of the origin of life, as well as a whole book^° pub-
lished in 1938. He arrived at similar conclusions. In his
book Beutner suggests that powerful electric discharges which
occurred at some time on the surface of the Earth might have
led to the formation of innumerable multitudes of organic
substances. Among these substances, which ^vere dissolved
in the waters of the primitive ocean, there might chance to
have been formed, at first simple enzymes, but later, enzymes
which were capable of reproducing themselves — self-regener-
ating enzymes. These ^vould have been exactly like the filter-
able viruses of the present day. Through their growth and
increase in complexity these original unimolecular forms of
living matter would also have served as the basis for the
formation of organisms endowed with a definite characteristic
structure.
Among French authors A. Dauvillier should be mentioned
here. As early as 1938 and 1939 he brought out papers con-
nected with our problem in the periodical L' Astronomies^
In 1947 he published a whole book on the subject." Like
many previous authors Dauvillier considered that the source
of the organic substances on the surface of the Earth was
carbon dioxide which was reduced to formaldehyde by
ultraviolet radiation. Dauvillier thought that a considerable
amount of formaldehyde might have been formed in this way
and that nitrogenous substances might have combined with
it as a result of electrical discharges. Nitrogen, in the form
of ammonia, could also enter into direct combination with
carbon dioxide under the influence of ultraviolet radiation.
This would also bring about the polymerisation of the
developing organic molecules.
Organic compounds of high molecular weight were thus
formed in the primaeval ocean. By virtue of their Bro^vnian
movement the colloidal particles were able to group them-
selves together in the most diverse ways. In the course of
many thousands of years there could have occurred, by
7
98 A SCIENTIFIC APPROACH
chance, juxtapositions of particles which had the structure
of the simplest organisms. Dauvillier adduced the crystallisa-
tion of glycerine as an example of such configurations arising
by chance. Although glycerine had been known since the
eighteenth century, for a long time it had only existed in
liquid form. The first crystals of glycerine were found in a
barrel which was sent from Vienna to London. This sudden
crystallisation was due to an unusual combination of move-
ments which occurred, purely by chance, in the barrel. Since
that time the spontaneous crystallisation of glycerine has only
been observed two or three times in all. It is, however, easy
to obtain crystals of glycerine by seeding liquid glycerine
with a pre-existing crystal. Dauvillier pointed out that pure
chance thus seems to be the most important creative factor.
" Here ", he wrote, " we see once more the handiwork of a
strange creator who is dependent on nothing but time ".
According to Dauvillier the first configuration of living
material, which arose by chance, must have had the pro-
perties of filterable viruses, that is, it must have had the
power to reproduce its own structure. As time went on these
centres of chemical activity gave rise to the development of
mitochondria and then to the formation of bacilli.
The author himself admits that the formation of such a
' living configuration ' endowed with the powers of metabol-
ism and self-reproduction, as a result of the chance com-
bination of organic molecules, seems a highly improbable
event. He considered that it could only have happened once
in the whole time the Earth has existed. After this there
occurred only the constant multiplication of this substance
which had arisen once and for all and was eternal and un-
changing.
G. W. Beadle" subscribed to the same ' molecular ' theory
when he wrote in 1 949 :
Somehow, out of this age-long trial and error process there
presumably arose molecules with the property of duplicating
themselves, that is, capable of catalyzing the process by which
they were formed. If such molecules were at the same time
sufficiendy large and appropriately built to permit chemical
modification without loss of the power to multiply their kind
EVOLUTIONARY THEORIES 99
systematically they would become ancestors of further lines of
evolution, now definitely organic.
This attitude was also adopted by H. Blum^^ in his interest-
ing book Time's arrow and evolution (1951), though he also
brought up the question of whether or not the primiti\e
autocatalytic molecules should be regarded as living.
In a recently published article H. J. Muller^^ again affirms
his earlier hypothesis, which we have already discussed, as
to the random emergence of one successful gene among
myriads of types of molecules.
It is, however, difficult to accept an idea of this kind, in
the first place because it completely shuts the door on the
scientific study of the most important event in the history
of our planet, which was the first emergence of organisms.
How can one study a phenomenon which, at best, can only
have occurred once in the whole lifetime of the Earth?
Physicists assert, in principle, that it is possible that the
table on which I am WTiting might rise into the air as the
result of the chance parallel orientation of the thermal
motion of all its molecules. It is, however, hardly likely that
anyone will allow for this possibility in his experimental
work or general practical activities.
A theory is of special value to the scientist if it opens up
practical possibilities for research by verifying the regular
occurrence of phenomena, either by observing nature or by
setting up suitable experiments in the laboratory. The con-
ception of the chance development of living molecules is
quite unproducti\ e practically.
In contradistinction to this, the evolutionary approach to
the problem of the origin of life opens up to the scientist
wide possibilities for the study and experimental reproduc-
tion of the separate stages of the long course of development
of matter which led up to the first appearance of living things
on the Earth.
During the last few years the evolutionary approach to
the solution of the problem in which w^e are interested has
attracted the minds of wider and wider circles of scientists
throughout the world. It is expressed in the flow of books
and papers, scientific reviews and experimental researches
lOO A SCIENTIFIC APPROACH
which are now appearing in the world literature in greater
and greater numbers. It is not only biologists who take part
in these investigations but also physicists, astronomers, geolo-
gists and chemists having different specialised interests.
In this chapter we can only enumerate briefly a few of
these researches and reviews. They are discussed in more
detail in the appropriate places in later chapters.
First we must mention the work of H. C. Urey.^® Starting
from an analysis of the thermodynamic and kinetic laws and
the geophysical and geochemical results which can be deduced
from them, he drew a picture of the primary formation of
organic substances in the course of the development of the
Earth, and of their further evolution in the first period of its
existence. These studies served as a basis for the very valuable
experimental work of S. L. Miller" who synthesised amino
acids from those gases which may be presumed to have been
present in the original atmosphere of the Earth.
In his well-known book The physical basis of life/^ and in
a number of later papers^^ and pronouncements,^" J. D.
Bernal approached the problem of the origin of life from a
physical and physico-chemical standpoint. He cast light on
many of the stages of the evolution of organic-chemical
substances and put forward very interesting ideas about the
first development of asymmetry in organic substances and the
possibility of their being adsorbed on particles of clay in
primaeval pools. In a recently published article V. M.
Goldschmidt" threw light on the geological aspects of the
problem.
A great deal of work has been done towards explaining the
general evolution of matter leading up to the development of
living things. According to their own specialities the authors
concentrated on the explanation of one or another stage of
this historical process. We may mention here the numerous
papers by N. W. Pirie,^^ J. B. S. Haldane,^^ R. Lemberg,^^
and the reviews of U. N. Lanham," G. Wald,^« S. Kirkwood,"
F. Cedrangolo^^ and many others. In his experimental work
J. J. Scott" pays great attention to the possible way in which
porphyrins might have developed. A. Gulick'" and L. Roka'^
consider the formation of high-energy phosphorus compounds
and polynucleotides ; while G. Ehrensvard" and S. Akabori'^
EVOLUTIONARY THEORIES lOl
are interested in tlie primary development of protein-like sub-
stances.
The investigation of open systems and the way in which
they develop is of great significance for the problem we
have been studying. These systems may serve as basis for
the development of metabolic activity, which is the form of
movement of matter characteristic of life. In this connection
the ^vorks of C. N. Hinshelwood,'^ I. Prigogine," J. W. S.
Pringle'* and others are of great interest.
The most important, as well as the least studied, stage of
the evolutionary process under consideration would seem to
be the transition from the most complicated organic sub-
stances to the most primitive living organisms. This is the
most serious gap in oiu' knowledge.
When we regard the organisation of any living thing, even
the simplest, it strikes us that this organisation is not only
very complicated but extraordinarily well adapted to the
fulfilment of the functions peculiar to life. It is directed
towards the continuous self-preservation and self-reproduc-
tion of the whole living system under given external con-
ditions.
The emergence of such internal ' adaptation of form to
function ' can only be understood on the basis of the same
principles which cause the ' adaptation of form to function '
in the structure of all the organs of all higher organisms.
That is to say, one must study the interactions between the
organism and its environment and apply the Darwinian
principle of natural selection. This new biological ^vay of
behaviour must have been developed in the inorganic world
as part of the process of the establishment of life and later
played a very important part in the development of all living
matter.
A number of authors such as N. H. Horowitz^ ^ and M.
Calvin^^ are trying to apply the principles of evolution and
even natural selection to individual molecules. However,
other workers (N. Kholodnyi,^^ J. D. Bernal, J. B. S. Haldane,
G. Wald and A. Oparin*°) consider that multimolecular
systems (' subvital ' systems, to use Haldane's terminology)
must have been formed before life arose and that these were
converted into living things by natural selection.
102 A SCIENTIFIC APPROACH
Apart from work directly bearing on the problem of the
origin of life, general biochemical studies have had tremen-
dous importance in its clarification. This is particularly true
of comparative studies of the metabolism of organisms at
different stages of evolution.
On the basis of the successive stages in the evolution of
metabolism we can put forward certain hypotheses concern-
ing the forms of organisation which preceded the appearance
of the first living things. An anatomist who studies and
compares the structure and organs of different animals can
draw a picture of their evolutionary development. Similarly,
a biochemist who studies the processes underlying various
vital phenomena can draw a picture of the successive stages
in the evolution of matter which led up to the emergence
of living beings.
In the rest of this book I try to give a picture of this evolu-
tion as it appears in the light of the scientific evidence now
available.
BIBLIOGRAPHY TO CHAPTER III
1. T. H. Huxley. Rep. Brit. Ass.^ iSyo, Ixxxiii.
K. V. Thimann. The life of bacteria. New York, 1955.
2. J. Tyndall. Rep. Brit. Ass., iSy^, Ixvi.
3. J.-B.-P. Ant. de Monnet Lamarck. Philosophie zoologique.
Paris, 1809.
4. J. O. DE LA Mettrie. Ocuvres philosophiques. Berlin, 1796.
D. Diderot. Pensees sur V interpretation de la nature. Lon-
don, 1754.
5. J.-B.-P. Ant. de Monnet Lamarck. Systeme analytique des
connaissances positives de I'homme restreintes a celles
qui proviennent de ['observation. Paris. 1820. Cf.
A. Studitskii. Uspekhi sovremennoi Biol., ^g, 3
(1955)-
6. (L 47)-
7. F. Darwin. Lije and letters of Charles Dariuin. Vol. 3, p. 168.
London, 1887.
8. C. Darwin. On the origin of species by means of natural
selection. London, 1859.
9. E. Haeckel. Generale Morphologic der Organismen. Berlin,
1866.
10. (L 60).
BIBLIOGRAPHY IO3
11. W. Preyer. Nalurivissenschajtliche Thatsachen und Prob-
leme. Populdre Vortrage. Berlin, 1880.
12. (in. 7). Vol. 3, p. 18 (footnote). Cf. G. Hardin. Sci. Mon.
AT.F., 70, 178(1950).
13. F. J. Allen. What is life? Proc. Bgham nat. Hist. Soc, 11, 44
(1899)-
14. H. F. OsBORN. The origin and evolution of life. London,
1918.
15. W. Francis. Proc. roy. Soc. Q_d., ^y, 98 (1925).
16. R. Dubois. C.R. Soc. Biol., Paris, ^6, 697 (1904).
17. M. KucKUCK. Losung des Problems der Urzeugung. Leipzig,
1907.
18. E. Pfluger. Pflilg. Arch. ges. Physiol., 10, 251, 641 (1875).
19. V. L. Kretovich, a. a. Bundel', S. S. Melik-Sarkisyan and
K. M. Stepanovich. Biokhimiya, ig, 208 (1954)-
A. A. Bundel', M. P. Znamenskaya, and V. L. Kretovich.
Doklady Akad. Nauk S.S.S.R., 82, 109 (1952).
20. A. Weismann. Die Continuitdt des Keimplasmas als Grund-
lage einer Theorie der Vererbung. Jena, 1885.
21. A. Weismann. Das Keimplasma. Jena, 1892.
22. A. Weismann. Vortrage ilber Deszcjidenztheorie. Jena, 1902.
23. C. Mereschkowsky. Biol. Zbl., 50, 278, 321, 353 (1910).
24. E. A. Minchin. Rep. Brit. Ass., 191$, 437.
25. L. JosT. Vorlesungen ilber Pflanzenphysiologie. (2nd edn.)
Jena, 1908 ; Lectures on plant physiology (trans.
R. J. H. Gibson). Oxford, 1907 (with Supplemettt.
Oxford, 1913).
26. A. Fischer. Fixierung, Fdrbung und Bau des Protoplasmas.
Jena, 1899.
27. L. Pasonov and V. Aleksandrov. Reaktsiya zhivogo vesh-
chestva na vneshnie vozdeistviya. Moscow and Lenin-
grad (Izd. AN SSSR), 1940.
28. M. Traube. Zbl. med. Wiss, 1866, pp. 97, 113 ; Arch. Anat.
Physiol., Lpz., iSSy, pp. 87, 129.
29. O. BiJTSCHLL Untersuchungen ilber mikroskopische Schdume
und das Protoplasma. Leipzig, 1892.
30. L. Rhumbler. Ergebn. Anat. EntivGesch., i^, 1 (1905).
31. S. Leduc. Les bases physiques de la vie. Paris, 1907; Theorie
physico-chimique de la vie. Paris, 1910 ; Solutions
and life. Colloid Chemistry, Vol. 2, p. 59 (ed. J.
Alexander). New York, 1928.
32. A. L. Herrera. Plasmogeny. Colloid Chemistry, Vol. 2,
p. 81 (ed. J. Alexander). New York, 1928.
104 A SCIENTIFIC APPROACH
33. A. L. Herrera. Bull. Lab. Plasmog. Mex., i, 49, 63, 71
(1934-5)-
34. A. L. Herrera. Science, ^6, 14 (1942).
35. F. Engels (I. 59).
36. V. Belyaev. O pervichnom zarozhdenii. Warsaw (Izd. Varsh.
Universiteta), 1893.
37. E. A. Schafer. Rep. Brit. Ass., 1912, 3.
38. K. TiMiRYAZEV. Iz nauchnoi letopisi 1912 god. Sobranie
Sochinenii, Vol. 7, p. 447. Moscow (Sel'khozizdat),
1939-
39. P. Becquerel. Astronomie, ^8, 393(1924).
40. A. I. Oparin. Proiskhozhdenie zhizni. Moscow (Izd. Moskov-
skii Rabochii), 1924.
41. J. B. S. Haldane. The origin of life. Rationalist Annual, 7929.
Repeated in: The inequality of man. London, 1932 ;
Science and human life. New York and London,
1933-
42. A. Adel and V. M. Slipher. Phys. Rev., 46, 902 (1934)-
43. T. H. Morgan. The theory of the gene. New Haven, Conn.,
1926.
44. H. J. Muller. The gene as the basis of life. Proc. 4th Int.
Congr. Plant Sci. (Ithaca, N.Y., 1926), i, 897 (ed. B. M.
Duggar). Menasha, Wis., 1929.
45. H. J. Muller. Proc. roy. Soc. Lond., 134B, 1 (1947)-
46. C. B. LiPMAN. Sci. Mon.,N.Y., ip, 357 (1924).
47. J. Alexander and C. Bridges. Colloid Chemistry, Vol. 2,
p. 9 (ed. J. Alexander). New York, 1928.
48. J.Alexander. Science, g6, 2^2 (1^4.2).
49. R. Beutner. Biodynamica, Vol. 2, no. 38, p. i (1938).
50. R. Beutner. Life's beginning on the earth. Baltimore, Md.,
1938-
51. A. Dauvillier. Astronomic, ^2, F,2q (iQ^S).
52. A. Dauvillier. Genese, nature et evolution des planetes.
Paris, 1947 ; Cosmologie et chimie. Paris, 1955.
53. G. W. Beadle. Genes and biological enigmas. 5c/. in Progr.,
6, 184 (1949)-
54. H. Blum. Time's arrow and evolution. Princeton, N.J.,
1951-
55. H.J. Muller. Science, 121, 1 (1955).
56. H. C. Urey. Proc. nat. Acad. Sci., Wash., ^8, 351 (1952).
57. S. L. Miller. Science, iiy, 528 (1953).
58. J. D. Bernal. The physical basis of life. London, 1951.
59. J. D. Bernal. The origin of life. New Biol., 16, 28 (1953).
BIBLIOGRAPHY
105
60. J. D. Bernal. Sci. & Cult., ip, 228 (1953).
61. V. M. GoLDSCHMiDT. Neiv Biol., 12, 97 (1952).
62. N. W. PiRiE. Discovery, i^, 1 (1953) ; New Biol., 16, 40
(1953)-
63. J. B. S. Haldane. New Biol., 16, 12 (1953).
64. R. Lemberg. Aust. J. Sci., i^, 73 (1951).
65. U. N. Lanham. Amer. A^at., 86, 213 (1952).
66. G. Wald. Sc/. /imer.;, August, p. 44 (1954).
67. S. KiRKWooD. Chem. Can., 8, No. 2, p. 25 (1956).
68. F. Cedrangolo. Nuova Antol., 19^6, p. 601.
69. J. J. Scott. Biochem. J., 62, 6P (1956).
70. A. GuLiCK. ^4/n^r. 5fz>»i.^ ^5, 479 (1955).
71. L. RoKA. J'ergleichend biocliemische Fragen, p. 1. 6. Collo-
quium der Gesellschajt filr physiologische Chemie
am 20-22 April ^955 in Mosbach /Baden. Berlin
(Springer), 1956.
72. G. Ehrensvard. Personal communication.
73. S. Akabori. Communication to Japanese Congress of Bio-
chemists. November 1955.
74. C. N. HiNSHELWOOD. The chemical kinetics of the bacterial
cell. Oxford, 1947.
75. I. Prigogine. Introduction to thermodynamics of irreversible
processes. Springfield, 111., 1955.
76. J. W. S. Pringle. Symp. Soc. exp. Biol., y, 1 (1953) ; New
Biol., 16,^4 (1953).
77. N. H. Horowitz. Proc. nat. Acad. Sci., Wash., ^i, 153 (1945).
78. M. Calvin. Chemical evolution and the origin of life.
Transcription of address delivered at Amherst Col-
lege, i9/ii/54r'^niversity of California, Berkeley,
Calif., 1955.
79. N. Kholodnyi. Uspekhi sovremennoi Biol., ip, 65 (1945).
80. A. I. Oparin. V ozjiiknovenie zhizni na zemle. (2nd edn.)
Moscow and Leningrad (Izd. AN SSSR), 1941 ;
Vestnik Moskovskogo Universiteta, ^-^, 193 (1955).
CHAPTER IV
THE ORIGINAL FORMATION OF
THE SIMPLER ORGANIC SUBSTANCES
The question of the original formation
of organic substances.
As a starting point for the study of the stages in the develop-
ment of matter which led at some time to tlie emergence of
life on the Earth, it seems best to begin by attacking the
problem of the original formation on our planet of the
simplest organic substances. Without these, life, as we know
it, is impossible and inconceivable.* All living beings, with-
out exception, have these substances as their basis. Moreover
metabolism, a phenomenon especially characteristic of life,
consists essentially of conversions involving organic com-
pounds. The very term ' organic substances ' was introduced
into the vocabulary of science because it expresses so well the
intimate relationship between these substances and living
organisms.
The famous S'^vedish scientist J. J. Berzelius,^ when defin-
ing organic substances in 1827, stated that this class of
substances can only be formed in living organisms under
the influence of the special ' life force ' which there prevails.
But this incorrect and idealistic view was dispro\ed by
Berzelius' contemporary and pupil F. Wohler^ who syn-
thesised first oxalic acid and then urea under laboratory
conditions without the participation of living beings.
After Wohler, syntheses of many diverse and sometimes
quite complicated organic compounds were carried out by
Kolbe, Butlerov and, especially, by M. Berthelot, who
was the first to prepare such compounds starting from their
component elements.* These and many other chemists
* There was at one time an exchange of opinions both in scientific and
popular ^vritingsi as to whether organisms formed from silicon com-
pounds could exist. This is no more than speculation, having neither
a factual nor a theoretical basis. — Author.
107
108 SIMPLER ORGANIC SUBSTANCES
during the nineteenth and twentieth centuries accomplished
artificial syntheses of substances characteristic of living organ-
isms. Among these were the various sugars, amino acids,
lipids, numerous pigments derived from plants and animals
including alizarin, indigo and substances responsible for the
colours of flowers, fruits and berries, also substances respons-
ible for their flavours and scents, numerous acids, terpenes,
tanning substances, as well as alkaloids, resins, rubber and
many other substances. In recent times some very compli-
cated compounds, having intense biological activities, such
as vitamins, antibiotics and hormones, have also been syn-
thesised in the laboratory.
At the same time the organic chemists also synthesised
substances which have never been found in any living organ-
ism, and thus have no direct relationship with living beings.
These, nevertheless, may be strikingly similar in their pro-
perties to substances originating from plants or animals.
Thus in many works of reference and text books^ ' organic
chemistry ' is defined as the chemistry of compounds of
carbon, since this element is present in all natural and arti-
ficial substances of this kind without exception.
However, carbon is not only found in nature in the form
of its organic compounds. It also enters into the composition
of such substances as marble and metal carbides, that is, into
the composition of substances that have a manifestly inor-
ganic, mineral character. A much more accurate definition
of organic chemistry would appear to be that first given by
Carl Schorlemmer^ as ' the chemistry of hydrocarbons and
their derivatives '. This definition not only emphasises the
fact that any organic compound can be derived from some
hydrocarbon, but has another distinct advantage. It distin-
guishes the specific quality of organic chemistry, as a branch
of science concerned with investigating a higher stage in the
organisation of matter than that studied by inorganic chemis-
try.'
From this point of view, organic chemistry is not simply
the chemistry of one of the elements from Mendeleev's
periodic table. It exhibits special, characteristic regularities
which first manifest themselves on passing from the inorganic
to the organic compounds of carbon.
FORMATION OF ORGANIC SUBSTANCES IO9
This transition seems, moreover, to have been the first and
most important stage in that development of matter which
led up to the emergence of life. Therefore, in approach-
ing the problem with which we are concerned, we should
first of all clarify our ideas on the following question : What
were the natural conditions during the formation of the
Earth or in the early stages of its existence which led to the
emergence of the hydrocarbons and their simplest deriva-
tives? For these are the carbon compounds from which
there could later arise all those other extremely complicated
organic stibstances which form the material basis of life.
Comparatixely recently, about twenty or thirty years ago,
that first step on the path towards the origin of life seemed
to be quite inaccessible to serious study. The majority of
scientists of the late nineteenth and early twentieth centuries
were firmly convinced that under natural conditions organic
substances could only arise by biogenesis, i.e. through the
agency of living beings. To some extent they were echoing
.early vitalistic views from the time of Berzelius, but their
attitude was mainly based on extensive and reliable observa-
tions of nature.
These observations show quite definitely that at present
the overwhelming bulk of organic substances arises on the
surface of the earth as a result of photosynthesis. Green plants,
by means of the energy of sunlight, use an inorganic car-
bon compound (carbon dioxide) to synthesise all the organic
stibstances necessary for their life and growth. Animals obtain
these substances from plants, either eating them as such or
maintaining themselves on the bodies or residties of plant-
eating creatures. The same sources of nourishment serve
for those other macro- and micro-organisms which are classed
as parasites and saprophytes.
Almost until the end of the nineteenth century photo-
synthesis was regarded as the exclusive source of all the or-
ganic substances on the Earth. Summing up the extensive
factual information on photosynthesis which had already
accumulated, K. Timiryazev, in his famous book The life of
plants,^ pointed out that the green leaf should be regarded
as " a unique natural laboratory in which organic substance
is prepared for both the plant and animal kingdoms ".
no SIMPLER ORGANIC SUBSTANCES
In 1887 and later S. VinogradskiP (Winogradsky) discovered
another source, likewise biogenic, for formation of organic
substances on the Earth. This is the so-called ' chemo-
synthesis '. Vinogradskii established the natural occurrence
of a special physiological category of bacteria, which can
synthesise the organic substances of their own bodies, using
carbon dioxide as their source of carbon, in darkness and
quite independently of light. This they do by making use
of energy obtained by bringing about the oxidation of vari-
ous mineral substances — some of the more reduced com-
pounds of sulphur, iron or nitrogen.^"
Nevertheless, detailed quantitative estimates of the vari-
ous ' nutritional chains ' or attempts at ascertaining overall
production of organic substances for the whole surface of the
Earth have been made in years gone by^^ and more recently. ^^
All these lead to the conclusion that photosynthesis by green
plants is by far the most important source of organic sub-
stances for the living beings which at present inhabit the
Earth.
Moreover, photosynthesis has also been responsible for
the development of various formations such as coal, which
might appear, at first sight, to be mineral in nature. Chemical
investigation of organic substances entering into the com-
position of coal (particularly lignin), geological study of its
distribution in the crust of the Earth and palaeontological
study of the numerous fossils obtained from it all agree in
pointing to a biogenic origin. The various coals are seen to
be derived by far-reaching decomposition and alteration of
what was originally mainly residues of plants. These became
buried in the crust of the Earth, being subjected at first to
the action of micro-organisms and later to high temperature
and pressure from the surrounding strata. ^^
The biogenic origin of petroleum is more controversial.
From the time of M. Berthelot^^ and D. Mendeleev^^ up to
the present there has been a lively scientific discussion of this
problem. However, most of the authoritative chemists and
geologists who have been concerned with this problem (see,
for example, C. Engler," A. Arkhangel'skii," V. Ver-
nadskii,^* N. Zelinskii,^^ G. Stadnikov,'" I. Gubkin^^^ and
others) consider that there is no doubt at all that at least the
FORMATION OF ORGANIC SUBSTANCES 111
bulk of the organic compounds present in petroleum have
been formed secondarily by alteration of the constittient sub-
stances of plants or animals ^vhich at some time inhabited the
Earth.
A proof of this is afforded by the recognition in petroleum
of numerous compounds which are characteristic of living
organisms. These include porphyrins and quinolines and
also a number of other compounds of nitrogen, sulphur,
phosphorus and oxygen whose nature suggests that they are
biogenic. The optical activity of several of these compounds
is also that characteristic for living organisms. The isotopic
composition of petroleum suggests the same, for the ^^c : ^-c
ratio is very close to that which we find in living organisms. ^^
Finally, the manner in which petroleum deposits are distri-
buted in sedimentary formations has also convinced many
geologists that their origin is biogenic.
Summing up all the evidence at our disposal, we may
conclude that, under natural conditions, the conversion of
carbon from its inorganic to its organic compounds is only
effected by the agency of living beings.
This conclusion set an enormous obstacle in the path of
solving the problem with which we are concerned. It appeared
necessary to assume that the first organisms to develop on
the Earth must have been autotrophs — that is, beings capable
of satisfying their own nutritional requirements from in-
organic compounds; organic substances were held to have
appeared on the Earth only as a result of the activity of living
organisms.
We find this point of view expressed by the overwhelming
majority of authors around the beginning of the present
century when they wrote about the primaeval forms of life
which w^re the original inhabitants of the Earth. The
' biophores ' of A. Weismann,-^ the ' biococci ' of S. Meresch-
kowsky'* and E. Minchin,^' the primaeval organisms of F.
Allen,"" H. Osborn,^'' V. Omelyanskii,"' W. Francis" and
others — all these hypothetical living beings must have arisen
all of a sudden, being formed directly from inorganic com-
pounds and have forthAvith proved capable of constructing
the materials of their bodies out of such compounds.
Many botanists, for example van Tieghem'° in France and
112 SIMPLER ORGANIC SUBSTANCES
Academician V. Komarov^*^ in the U.S.S.R., have Hkened the
appearance of Hfe on the Earth to a process which occurs
nowadays in a number of places, namely the first colonisa-
tion of newly exposed rock formations. In his book The
origin of plants Komarov very vividly describes the first
colonisation of lifeless volcanic deposits in Kamchatka. Here,
in the waters of hot springs, which emerge into the light of
day among heaps of lava and pumice, can be found blue-
green algae and colonies of thermophilic bacteria, all cap-
able of growth on purely mineral media.
The analogy between such organisms and the hypotheti-
cal first living beings to arise on the Earth appears very
widely in the literature of science up till comparatively
recently. This reflects a deep conviction that the Earth,
before the appearance of life, was also completely devoid of
organic substances, like these naked lifeless rocks. In fact,
this analogy is completely false. For the rocks are known to
be continually receiving the spores and seeds of both lower
and higher plants. The fact that some of these develop while
others do not simply demonstrates the selectivity of the
environment. Under these particular conditions only auto-
trophic organisms can develop. This is easy to understand,
since no organic substances are present. Moreover, it is clear
that the extremely complicated organisation which makes
autotrophy possible among present-day organisms is the
result of a prolonged evolution of those living beings which
produced the spores and seeds arriving on the bare, lifeless
rocks. We are in complete disagreement with the theory of
' panspermia ', which implies the transference of ready-made
spores to a lifeless Earth. How then, in the absence of such
transference, can we imagine the direct formation of auto-
trophic organisms from inorganic matter, which would imply
the sudden development of systems embodying a most com-
plicated organisation of metabolism?
In a recently published and very relevant paper D. D.
Woods and J. Lascelles''^ pointedly remark that if autotrophs
are the most primitive living creatures on the Earth, then
" something must be imagined analogous to the birth of the
Goddess Athene who, you may remember, sprang forth fully
armed (in war-gear golden and bright) from the head of
FORMATION OF ORGANIC SUBSTANCES I13
Zeus ". This implies that the autotrophs must suddenly have
appeared in an inorganic medium, completely equipped
with the most complicated biochemical systems and morpho-
logical structure required for the autotrophic synthesis of
organic substances.
The extreme complexity of organisation of those living
beings which are capable of photosynthetic assimilation of
carbon dioxide is evident not only to the biochemist but also
to the morphologist. It long ago forced itself on the attention
of the botanical systematists. On purely morphological
grounds many of them denied that such organisms could be
the prime ancestors of life on the Earth. Others, ho^s^ever,
assigned to this role one or another of the more primitive
groups of photo-autotrophs because they imagined that the
primaeval living beings must have been capable of main-
taining themselves on inorganic substances. In this they
paid insufficient attention to the facts of comparative mor-
'phology, or even flew in the face of these facts (see, for
example, the review by A. Pascher^^).
The inherent weakness of this position was very much
felt by a number of biologists during the closing years of the
nineteenth century. Consequently, when S. Vinogi'adskii
discovered the chemosynthetic bacteria, they were quick and
keen to proclaim these as the primaeval organisms. This
seemed to resolve the dilemma that, while the primaeval
organisms must, according to prevailing views, have been
autotrophic in their nutritional requirements, the organisa-
tion of cells capable of photosynthesis is manifestly far from
primitive.
The hypothesis that the chemoatitotrophs were the first
organisms to inhabit our planet has remained current up to
the present time and is to be found in several widely read
revicAvs (e.g. those of C. H. Werkman and H. G. Wood,^'*
M . Stephenson,^^ W. O. Kermack and H. Lees"^ and others).
In the light of present-day biochemical knowledge, how-
ever, the facts suggest that chemosynthesis, like photo-
synthesis, requires a far more complicated and specialised
biochemical organisation than does heterotrophy (the use of
preformed organic substances). Chemoautotrophs can make
use of organic substances; this ability is fundamental to the
114 SIMPLER ORGANIC SUBSTANCES
biochemical organisation of these and other living things."
Even those few forms of bacteria which are unable to exist at
the expense of organic materials derived from the external
medium, such as Thiobacillus thio-oxidans, can nevertheless
oxidise their intracellular reserves of polysaccharides during
the process of respiration.^* This breakdown is associated
with the same enzymic apparatus, the same metabolites of
glycolysis, the same vitamins, adenosine triphosphoric acid,
etc., which take part in the metabolism of heterotrophs.^^
The inability to assimilate organic substances from the sur-
rounding solutions seems, in this case, to be due merely to
a peculiar type of permeability of the external membranes
of the bacteria in question. The metabolism of all autotrophs
is based on a biochemical system for the degradation of
organic substances which seems to be extremely primitive
and general. The chemosynthetic apparatus would appear
to be a secondary, supplementary development which in-
increases the complexity of the metabolism. The existence of
autotrophic forms within the most systematically diverse
groups of micro-organisms also indicates that they have a
hereditary relationship to the heterotrophs from which they
arose, and that in the course of evolution they have acquired
the power to make use of the energy of oxidation of reduced
mineral substances. It now seems quite impossible, even
from a purely systematic point of view, to suppose that the
whole plant and animal kingdoms were derived from the
chemosynthetic bacteria. Chemoautotrophy must undoubt-
edly be regarded as an offshoot of the evolutionary process.*"
Even among systematists there is, at present, no unanimity
as to which of the existing forms of organism are closest to the
prime ancestor of life on the Earth. Many workers think the
flagellates are the most primitive (e.g. V. Dogel',*^ L. Kursanov
and colleagues,*^ A. Lwoff*^) ; others think the Sarcodina are
more primitive (e.g. A. Elenkin,** A. Zakhvatkin,*^ and A.
Markevich"**). All are, however, agreed that the obligate
heterotrophic organisms which do not require light are
the simplest existing organisms. The controversy is about
whether these simpler forms arose by degeneration of more
complicated ones or Avhether they are themselves nearer to
DISTRIBUTION OF ORGANIC SUBSTANCES 1 15
the original form of life and more complicated forms have
evolved from them.
As early as 1922 I expressed the view that all the difficulties
and contradictions which have been discussed were only
apparent and that the first living things to develop on the
Earth were quite able to nourish themselves heterotrophi-
cally on organic substances because these compounds must
have been formed abiogenically on the Earth long before
the appearance of life on it/^ The belief that organic sub-
stances could only be formed biogenically under natural
conditions was based on a preconception of the conditions
which prevailed on the Earth at the appropriate epoch in
its existence. If, however, we take a broader view of the
question and extend our studies beyond the limits of our
own planet to include facts concerning other heavenly bodies,
then this conception will be rudely shaken.
The distribution of organic substances
(hydrocarbons) on different
heavenly bodies.
Spectroscopic studies of the atmosphere of the stars have
long ago shown that carbon is very widely distributed
throughout the universe. It is to be found everywhere. It
has been shown recently that this element plays an extremely
important part in the life of stars. It is well known that
the source of stellar energy resides in particular reactions
taking place within the nuclei of atoms and that these take
place in the interior of the stars where temperatures of some
tens of millions of degrees prevail. Under these conditions
hydrogen is converted into helium with a resulting decrease
in mass and consequently with the release of enormous
amounts of intra-atomic energy.
H. A. Bethe'*^ states that reactions of this kind can only
take place in the presence of carbon which acts in a peculiar
way as a ' catalyst ' in this nuclear reaction. In the course
of this four hydrogen nuclei (protons) are converted into
helium with the liberation of a very large amount of intra-
atomic energy.
This so-called carbon cycle is the fundamental cause of
the shining of the stars which is therefore directly associated
n6 SIMPLER ORGANIC SUBSTANCES
with the presence o£ carbon. Any heavenly body having a
mass greater than one-twentieth of that of the Sun is very
likely to have such a cycle occurring within it, in which case
it will be a self-luminous formation, in fact a star.
It is of particular interest to us to enquire as to the form
in which carbon exists on stars of different spectral types.
On stars of type O, which have a very high temperature on
their surfaces, J. Plaskett*^ found that carbon was present
mainly in the singly or doubly ionised form (c+ or C++). On
these stars the temperature is so high that there can be no
question of the presence of any sort of chemical combination
of carbon. The carbon atoms themselves are substantially
altered in that they have lost some of their outer electrons.
On stars of type B, which are cooler, F. Henroteau and
J. Henderson^" also demonstrated the presence of carbon,
though only in the neutral form. However, no carbon com-
pounds could exist on these either. Signs of such compounds
appear in the spectra of stars belonging to type A. Traces
of g-bands (A, 4,314 A) were discovered in the spectra of
such stars quite a long while ago,^^ indicating the possibility
of the development there of the most primitive carbon com-
pounds— the hydrocarbons (methyn, ch). In the spectra of
other types of stars the hydrocarbon bands show up more
and more clearly as the temperature of the surface of the
star decreases, reaching a maximum clearness in the spectra
of types M and R. These spectra also reveal the presence of
compounds of carbon and nitrogen (cyan) in the atmospheres
of the stars.
In the spectra of the sim-spots, and even more so in the
spectra of stars of types N and R, there have also been demons-
trated the so-called Swan's bands which indicate the presence
of molecules consisting of two carbon atoms combined to-
gether (Ca, dicarbon).^^
The investigations of these bands by G. Shain" and later
workers have shown that the carbon in the atmosphere of
some so-called carbon stars is ten times richer in the heavy
isotope ^^c than the carbon in terrestrial objects. It follows
that the evolution of the nuclear material itself has followed
a somewhat different course on these stars from that which
it has followed within the solar system. Nevertheless, hydro-
DISTRIBUTION OF ORGANIC SUBSTANCES I17
carbons form one of the chief types of carbon compounds
in the atmospheres of these as of other stars.
Our Sun is classified as a star of type G (yellow stars). The
temperature of the atmosphere of the Stm is about 6,000° C.
The temperature of the outer layers is as low as 5,000° C,
while the innermost parts accessible to investigation reach
7,000° C. Spectroscopic studies show that even here a con-
siderable proportion of the carbon is present in the form of
compounds ^vith hydrogen (in the form of methyn, ch), and
there may also be more complicated compounds containing
several atoms of carbon and hydrogen. ^^
We thus see that compounds of carbon and hydrogen —
hydrocarbons — are very widely distributed in the atmospheres
of stars of various types. It is, however, clear that they must
have been formed abiogenically as there can be no question
of any vital processes taking place at temperatures of some
thousands of degrees, such as prevail on the surfaces of stars.
This wide distribution of hydrocarbons is also fotmd at
the other extreme of temperature within the universe, at
temperatures approaching absolute zero.
It is now well known that by no means all the matter of
our galaxy and other analogous systems exists in the form
of large aggregates such as stars and planets. A considerable
part of its mass (10 per cent or maybe far more) is scattered
through space in the form of very finely divided dust or
gas.^^ Clouds of cosmic dust are mainly concentrated in the
plane of the galaxy. Some of these are visible to the naked
eye, sharply outlined against the light background of the
Milky Way by virtue of their absorption of light.
It may be easily shown spectroscopically that atoms and
electrons in the interstellar gas in the neighbourhood of stars
of types O and B can attain very high speeds, corresponding
to temperatures of several thousands of degiees. In those
parts of interstellar space which are far away from hot stars
there are wide areas in which hydrogen exists in the un-
ionised form, the temperature of the gas in these areas
being no more than 50° - 100° Absolute (about —200° C).
This was established by direct measurement using radio
waves. ^® The temperature of the cosmic dust is even lower.
It never rises more than a few degrees above absolute zero.
ii8
SIMPLER ORGANIC SUBSTANCES
Collisions between atoms of gas and particles of dust there-
fore lead to a cooling of the gas, making it colder in the
presence of dust than in the absence of it."
The interstellar gas consists almost entirely of hydrogen
which is the most abundant element of the cosmos in general
(accounting for 90 per cent of its mass)/* The work of H.
Kramers and D. ter Haar^^ has shown that the simplest
hydrocarbon radicals, ch and ch+^ are formed in interstellar
space. However, H. C. Urey*" considers that, as a result of
the catalytic activity of the dust and the presence of large
amounts of hydrogen in the clouds of gas and dust, all free
radicals would be converted into stable molecules. He con-
siders it probable that methane is formed, although more
complicated hydrocarbon molecules may also occur. On the
basis of their own investigations D. R. Bates and L. Spitzer"
suggest that when a cloud of dust of the usual density moves
towards a hot star the temperature of the particles of dust
will rise and, at a particular distance from the star, the CH4
will evaporate and will later dissociate to give ch and ch+.
Thus we may observe the same widespread formation of
hydrocarbons, both in the incandescent atmospheres of the
stars and in the cold clouds of gas and dust. There can be
no possible doubt that the hydrocarbons were formed abio-
genically in these situations.
The position is the same within the narrower confines of
our own planetary system. Although it is difficult to study
the planets spectroscopically, a considerable number of facts
as to the chemical constitution of the atmospheres of the
planets has now been accumulated. As early as 1935 these
facts were brought together by H. N. Russell in his book
The solar system and its origin.^" The more recent discoveries
may be found in H. C. Urey's book The planets, their origin
and development, to which reference has already been made,
and also in the collection of papers edited by G. Kuiper and
published under the title The atmospheres of the Earth and
planets.^^
The planets of the solar system may be divided into two
groups according to their chemical composition: the group
of large planets, which includes Jupiter, Saturn, Uranus and
Neptune, and the group of planets resembling the Earth
DISTRIBUTION OF ORGANIC SUBSTANCES 1 IQ
which also includes Venus and Mars. Mercury occupies a
somewhat special position, in that it is a naked rocky mass
without an atmosphere, similar in some respects to our Moon
and Pluto, about the chemical composition of which we still
know very little.
When they were formed the large planets retained the
quantitative relationship between the various elements which
is characteristic of the galaxy as a whole. Thus the elements
which predominate in their composition are, first hydrogen,
and then the other light elements ; this is what causes their
characteristically low specific gi'avity and chemically reduced
state.
For a long time spectroscopic studies of these planets led
to no definite results. The bands which had been observed
in their spectra remained a puzzle and it was not until 1932
that R. Wildt showed that some of these bands in the spec-
trum of Jupiter corresponded with the bands of ammonia
and others with those of methane. This was soon confirmed
by T. Dunham, and then A. Adel and V. M. Slipher^^ suc-
ceeded in identifying all the bands characteristic of methane.
There could thus be no doubt as to the presence of the
hydrocarbon, methane, in the atmosphere of Jupiter. H. C.
Urey has shown that this methane must be converted photo-
chemically to other higher hydrocarbons, both saturated and
unsaturated. In particular, he showed that cuprene, a hydro-
carbon of high molecular weight having a red colour, would
arise by the polymerisation of acetylene. According to Urey
the presence of this substance would account for the colour
of the red spot on Jupiter. Owing to the temperature of
the surface of Jupiter, ^shich is very low compared to that
on the Earth (- 140° C), only methane can exist there in
the gaseous state. Even such hydrocarbons as ethane, ethy-
lene and acetylene are liquids under such conditions.
Saturn has an abundant atmosphere which, like that of
Jupiter, contains methane and ammonia, but as the distance
of this planet from the Sun is far greater, the temperature on
its surface is even lower than that on Jupiter. A considerable
proportion of the ammonia on Saturn is therefore in the solid
state, as may be seen from the spectrum, in which the
methane bands stand out very clearly.
120 SIMPLER ORGANIC SUBSTANCES
The temperatures are far lower on the surfaces of Uranus
and Neptune, which are still further from the Sun. The
ammonia is completely solidified but, on the other hand, a
very large amount of methane is present in their atmospheres.
Thus we find carbon in combination with hydrogen on all
the large planets. The discovery of methane in the atmo-
sphere of Titan, a satellite of Saturn, by G. P. Kuiper in
1944*^ is of very gi^eat interest. Titan is one-third of the
size of the Earth and has one-fortieth of its mass. It is only
the extremely low temperatures which prevail in the neigh-
bourhood of Saturn (— 180° C) which enable Titan to retain
its atmosphere of methane. It is clear that there can be no
question of biogenic formation of hydrocarbons here any
more than on the large planets.
In the atmospheres of the planets belonging to the same
group as the Earth the carbon is mostly oxidised and exists
in the form of cOg. Thus the proportion of this gas in the
atmosphere of Venus is many times greater than in that of
the Earth. According to Kuiper, there is reason to believe
that a certain quantity of methane and other hydrocarbons
of the acetylene and ethylene series are present in the
atmospheres of Venus and Mars. Here, however, one cannot
completely exclude the possibility that both the carbon di-
oxide and the organic substances have arisen biogenically.
The study of meteorites is of particular interest in connec-
tion with the problem under discussion ; in the first place
because meteorites which have fallen on to the Earth may
be submitted to direct chemical analysis and, further, to
mineralogical investigation. These are the only * non-terres-
trial ' bodies of which the composition may be established
with completeness and certainty. In the second place, a study
of meteorites shows us more and more convincingly that their
chemical composition is very close to that of the Earth as
a whole, and that their formation was related to that of our
own planet.
Long ago the attention of scientists was directed towards
the origin of the Earth and the meteorites. Many prominent
geochemists of the twentieth century, including F. W.
Clarke,'^ H. S. Washington," V. M. Goldschmidt,'« and I. and
W. Noddack," have studied the structure and composition
DISTRIBUTION OF ORGANIC SUBSTANCES 121
of meteorites from this point of view. In his book Geo-
chemistry A. Fersman^" gives an extensive review of these
investigations. He indicates the tremendous significance of
the study of meteorites in the solution of geochemical prob-
lems. He writes:
It may be that we are only now beginning to understand what
a very important part a thorough and well worked out analysis
of meteorites can play, both in determining the composition of
the Earth, and in clarifying the laws governing the difference
between the composition of the crust of the Earth and the
composition of the Earth as a whole. This is essential to a clear
understanding of the quantitative occurrence of the elements
in the parts of the crust of the Earth accessible to us.
A. Fersman presented a whole series of comparative analy-
ses of meteorites and of various terrestrial formations. These
figures revealed striking correspondence between the over-all
composition by weight of the Earth and the average composi-
tion of meteorites, a correspondence which cannot be acci-
dental. All this led him to the conclusion
that both in respect of the nature of their elements and in the
principle on which their atoms are built, the elements found in
meteorites are very similar to those found in the deepest zones
of the crust of the Earth, and that, in all probability, they
correspond even more closely to the central parts of the Earth.
These data have now been considerably amplified by the
inclusion of new analyses and the consideration of a number
of new circumstances (e.g. H. Brown and C. Patterson, ^^
H. C. Urey and H. Craig,'- and P. Chirvinskii'^). The basic
conclusions reached by Fersman remain, however, un-
changed. The reason for this close correspondence between
the chemical composition of the meteorites and that of the
Earth is certainly that both the Earth and the meteorites
developed from one and the same original material. Never-
theless, different authors have held different views on the
way in which meteorites were formed.
Most astronomers and geologists consider that meteorites
arose in the solar system by the disintegration of a ' mother '
planet, similar in composition to the Earth, but considerably
122 SIMPLER ORGANIC SUBSTANCES
smaller in size. This planet is assumed to have been formed
somewhere between the orbits of Mars and Jupiter. Its radius
is estimated at 2,500 - 3,000 km. and its mean density at
3-8 (S. Orlov,'* V. Fesenkov," A. Zavaritskii^^ and others).
R. A. Daly" even tried to build a model of this hypothetical
planet, analogous to the meteoritic model of the Earth,
having a core of iron and nickel enclosed in a geosphere of
silicates and basalt.
On the other hand O. Shmidt, B. Levin,'" and other
workers deny the possibility that meteorites were formed by
the disintegration of a ' mother ' planet, because they con-
sider such a disintegration physically inexplicable. They see
meteorites as splinter bodies like asteroids, formed at remote
stages of the evolution of the protoplanetary cloud, formed,
perhaps, in the same region as the Earth and therefore
having a similar over-all chemical composition.
Whichever hypothesis one supports, it is quite clear that
the study of the composition and structure of meteorites can
give a great deal of information relevant to the problem of
what were the primary compounds which appeared during
the formation of the Earth.
All meteorites are commonly allocated to two basic groups,
stony and iron. An intermediate group is sometimes recog-
nised, the iron-stony meteorites."
The iron meteorites are composed of so-called nickel iron,
which contains more than 90 per cent of iron, 8 per cent of
nickel, about 05 per cent of cobalt and small amounts of
phosphorus, sulphur, copper and chromium. In the stony
meteorites, which fall far more frequently on the Earth, the
percentage of iron is considerably lower. In these, silicates
and oxides of such metals as magnesium, aluminium, calcium,
sodium, etc., predominate. The discovery of 9 per cent of
constitutive water by A. Zavaritskii and L. Kvasha*" in the
Staroe Boriskino meteorite is of great interest.
Carbon has been found in meteorites whenever it has been
looked for. The amount present is sometimes as low as some
hundredths of 1 per cent but some so-called carbon meteor-
ites contain up to 2 or even 45 per cent of carbon.
As regards the isotopic composition of the carbon of
meteorites, the mean value of the ratio of ^^c to "c is 2 per
DISTRIBUTION OF ORGANIC SUBSTANCES 123
cent higher than that in terrestrial carbonates and 1-3 per
cent lower than that in biological objects. ^^ There is reason
to suppose that it approximates very closely to the original
isotopic composition of carbon on the surface of Earth and
that the divergence of the proportions of the isotopes of
carbon did not arise until the period in the history of our
planet when life had developed and biological processes were
taking place.
The forms in which carbon is commonly found on meteor-
ites are carbides and native carbon, either in the amorphous
state, or as graphite or diamonds. Graphite, in particular,
has been found in iron meteorites in the form of nodules,
flakes and granules which sometimes attain a weight of 1 2 g.
Erofeev and Lachinov were able to isolate about 1 per cent
of carbon in the form of diamond from the meteorites which
fell near the village of Novo-Urei in the province of Penza
in 1887. Later A. E. Foote and Koenig obtained diamond
dust from the meteorites which fell in the Diablo canyon in
Arizona. Weinschenk also found diamonds in the Magura
meteorites.*^
Weinschenk was also the first to find cohenite, a mineral
which is very widely distributed in and characteristic of
meteorites. It is a carbide of iron, nickel and cobalt and has
the general formula (Fe, ni, 00)30.
Cohenite is the parent substance of the free carbon and of
the hydrocarbons which have been found in a number of
meteorites.
As early as 1857 F. Wohler^-^ succeeded in isolating a
certain amount of organic material similar to ozocerite from
the stony meteorite which fell near Kaba in Hungary. Analy-
sis of this material showed definitely that it was composed
of hydrocarbons of high molecular weight. A similar ma-
terial was isolated from the meteorite which fell in Cold
Bokkeveld in Cape Province. This meteorite contained up
to 025 per cent of hydrocarbons. P. Melikov and V. Krshiz-
hanovskii*^ found a small amount of hydrocarbons in the
silicate meteorite which fell in the village of Migeya near
Elizavetgrad in the Khersonese in 1889. In his book von
Kliiber^* gives a general account of the occasions on which
hydrocarbons have been found in meteorites. In particular.
124 SIMPLER ORGANIC SUBSTANCES
J. L. Smith^'* succeeded in isolating a compound having the
composition C4HgS5 from the Orgeuil meteorite. Compounds
having the formula CgHgOa were found in the Orgeuil and
Hessle meteorites. The number of such finds increases from
year to year.
At the time when the presence of hydrocarbons in meteor-
ites was first discovered people were, as we have already
indicated, still firmly convinced that, under natural condi-
tions, organic substances could only arise biogenically. It
was not unusual, therefore, for scientists to put forward the
hypothesis that the hydrocarbons of the meteorites had been
formed secondarily as the result of the decomposition of
organisms which had lived on them at some time. We have
shown, however, in Chapter II, that all the numerous
attempts to find microbes, their germs, or any other organised
remains, have been quite fruitless. On the contrary, all the
experts on meteorites, such as A. Fersman, F. Levinson-
Lessing, V. Vernadskii and others, agree that there is nothing
in meteorites which resembles a sedimentary formation or
which could, in general, suggest the possibility of the exist-
ence of biogenic processes. It follows that the hydrocarbons
of the meteorites, like those of the cosmic dust, arose abio-
genically, that is to say, without any connection with organic
life.
A few words must still be said about comets. These
heavenly bodies originate somewhere in the neighbourhood
of the orbit of Pluto where the condensation of methane can
occur. According to F. L. Whipple*^ the nucleus of comets
consists of finely dispersed dust containing all the elements
which are commonly met with in the silicate and metallic
phases of meteorites.
There are also present in the nuclei of comets particles of
frozen liquids and gases, compounds of carbon, hydrogen,
nitrogen and oxygen.
When it approaches the Sun the substance of a comet
begins to emit light and can therefore easily be submitted
to spectroscopic investigation. The spectrum of the head of
a comet shows that it consists of chemical compounds. In
particular, hydrocarbon bands may be seen, indicating the
presence of ch., ch and ch+.
HYDROCARBONS FORMED A B lO GEN I C ALL Y 125
Here too, as in other heavenly bodies, we find hydro-
carbons, as was to be expected from a theoretical considera-
tion of the circumstances under which comets were formed.
In the light of all that has gone before we see that not only
is it perfectly possible that hydrocarbons could have been
formed abiogenically under natural conditions but this pro-
cess seems to be extremely widespread throughout the uni-
verse. Hydrocarbons have been found everywhere, on all
bodies accessible to investigation ; in the atmosphere of stars
of different spectral types, particularly in the atmosphere of
the Sun ; in the cold clouds of gas and dust in interstellar
space ; on the surfaces of the large planets and their satellites,
in the substance of comets and, finally, in meteorites falling
on the surface of the Earth. Is it possible that our planet
is an exception to this general rule and that the simplest
organic substances could never have arisen abiogenically on
it? Is it not more probable that this process took place in
the past before the appearance of life on the Earth and
perhaps still goes on although we do not notice it?
Geological finds of hydrocarbons
formed abiogenically on the Earth.
Most astronomers and geologists believe that in the centre
of the Earth, at a depth of 2,900 km., there is a nucleus
which is far denser than the superficial formations and which
is similar in chemical composition to the metallic (iron)
meteorites. This consists, for the most part, of iron and
nickel, with a small admixture of cobalt and other elements.
If it is assumed that carbon is present in the core of the
Earth, it is present there in the form of carbides of iron and
nickel similar to those in the iron meteorites (Fig. 9).
On the other hand, O. Shmidt^^ and a number of his
colleagues at the Geophysical Institute of the Academy of
Sciences of the U.S.S.R. consider that the outer parts of the
Earth and its core do not differ from one another in their
chemical composition but only in their physical state. Accord-
ing to Shmidt the differences in density, seismic and other
phenomena which have led people to postulate a nucleus in
the Earth could be due to phase transformations of siliceous
material into the metallic state brought about by the high
126
SIMPLER ORGANIC SUBSTANCES
pressure, rather than to gravitational layering out leading
to a separation of the various substances entering into the
composition of the Earth." However, neither Shmidt nor
any other contemporary scientist would deny the presence of
iron and nickel carbides in the composition of the Earth,
ROCKY
ENVELOPES
CENTRAL
NUCLEUS
ORE BEARING
ENVELOPES
CRUST OF
THE EARTH
ATMOSPHERE
Fig. 9. Diagram of the structure of the Earth.
because their presence is not merely based on theoretical
considerations, but is something which has been directly
proved by a number of geological findings.
As we have already mentioned, the mineral cohenite,
having the general formula (Fe, Ni, 00)30 was first found in
meteorites. As early as 1854, however, G. Forchhammer
pointed out the presence of carbides of iron and nickel in
native iron ores from Niakornak.***
In 1870 the Swedish traveller Nordenskjold found large
lumps of iron in the basalt at Ovifak on the island of Disko
HYDROCARBONS FORMED A B lO GEN I C A LL Y 1 27
off Greenland. Their chemical composition was similar to
that of iron meteorites but later studies have shown that they
were undoubtedly of terrestrial origin.*'
Numerous analyses of the ' Ovifak iron ', in particular the
work of J. L. Smith, ®° R. T. Chamberlin" and others, have
revealed the presence in it of nickel-containing carbides of
iron (cohenite). Carbides of this sort have also been found
in native iron derived from many different sources ; for
example, they have been found in native iron ore from
Santa Caterina and Kersut, in the basalts of Oregon and
Hawaii, in the geological formations of the Transvaal, etc.
" It is very probable ", wrote Vernadskii,'^ " that a more
detailed study of these minerals will show that they are
present everywhere in the deep basalts (the basaltic layer)."
It has already been mentioned that cohenite is the parent
substance both of the native forms of carbon (especially
graphite) and of the hydrocarbons present in meteorites. The
connection between terrestrial cohenites and hydrocarbons
can easily be understood from a purely chemical point of
view. As long ago as the nineteenth century M. Berthelot,®^
H. Abich,'* and H. Moissan'^ indicated the possibility that
hydrocarbons might be formed directly from the carbon of
carbides, and substantiated this by direct chemical experi-
ment. A great deal of work in this direction had been done
by D. Mendeleev.'^ As early as 1877 he described the reaction
leading to the formation of hydrocarbons, according to the
equation 3 ^^m ^n + 4mH20^mFe304 + CgnHgnj.
Mendeleev wrote as follows :
Cloez studied the hydrocarbons formed by dissolving pig
iron in hydrochloric acid and found representatives of the
series CnH,,, and other hydrocarbons. I treated crystalline man-
ganese-containing pig iron (containing 8 per cent of carbon) with
hydrochloric acid and obtained a liquid mixture of hydrocarbons
which, in its smell, appearance and reactions, was just like
natural petroleum.
On the basis of these reactions Mendeleev constructed his
well-known theory of the mineral origin of petroleum. He
wrote :
128 SIMPLER ORGANIC SUBSTANCES
When mountain ranges are raised, cracks opening upwards
are formed at the summit while, at the foot of the mountains,
the cracks open downwards. In the course of time they are filled
up but the younger the rocks . . . the fresher are the cracks, and
through them water can obtain access to parts of the interior
of the earth in a way which cannot normally happen (in plains).
Thus, according to Mendeleev, the water of the sea was
able to reach the red-hot central nucleus of the Earth which
contained large amounts of iron mixed with carbon ; and,
by reacting with the carbon, it gave rise to the hydrocarbons
of petroleum.
This theory has now been abandoned because it is contra-
dicted by a number of geological observations. It is hard
to imagine how the water could have trickled down to reach
the carbides of the nucleus of the Earth from which it was
separated by a layer of rock formations more than a thousand
kilometres thick. Apart from this, all the considerations
which we have already put forward about the isotopic com-
position of petroleum, its optical activity and other physical
and chemical properties, as well as the way in which deposits
of petroleum are laid down in sedimentary formations, show,
without doubt, that the main mass of the organic material
of petroleum arose secondarily as the result of alteration of
the substances of animals and plants which lived on the
Earth at some time.^^
Mendeleev's main contention that hydrocarbons could be
formed abiogenically by the action of water on carbides is
completely justified by both earlier and later studies. As
early as 1841 Schrotter obtained a liquid similar to petroleum
by the action of dilute acids on pig iron. This reaction was
later studied by H. Hahn.^* By dissolving a large quantity of
white iron in acid over several weeks he obtained a very con-
siderable amount of petroleum-like liquid. It is interesting to
note that in addition to his work cited by Mendeleev, S. Cloez
carried out experiments in which the formation of hydro-
carbons occurred during the decomposition of ferromangan-
ese containing 5 per cent of carbon under the action of super-
heated steam alone.'®
K. Kharichkov"" observed the formation of liquid and
gaseous hydrocarbons when aqueous solutions of chlorates
TI VDROCARBONS FORMED ABIO GEN I C ALL Y 1 29
and sulphates of manganese and sodium acted for a long time
in sealed tubes or stoppered bottles on powdered common
giey pig iron containing 3 per cent of carbon. Finally,
V. Ipat'ev"^ again repeated the reactions in which hydro-
carbons were obtained from iron which contained carbon
by the action of dilute hydrochloric acid, salt solutions and
plain steam.
A still greater amount of evidence of like character could
be adduced, but the facts which have been set out prove
conclusively enough that, under the conditions of chemical
experiments, treatment of carbides of iron and other metals
with dilute acids, solutions of salts or plain Abater will give
rise to the simplest organic substances, hydrocarbons, with-
out any connection with, or participation by, organisms.
Could such phenomena take place under natural condi-
tions on the Earth at the present time? Many leading
geologists and geophysicists have considered that this is
perfectly possible. For example, V. VernadskiP^ in his
Outlines of geochemistry wrote: " There are, however, facts
which show that metallic carbides, cohenites and perhaps
others, may also be thrown up in some volcanic formations
under conditions which do not preclude the formation of
hydrocarbons on reaction with hot water." Similarly, V. M.
Goldschmidt'"- in his recently published paper on the
development of organic substances indicated the possibility
that hydrocarbons may be formed by inorganic processes such
as the hydrolysis of metallic carbides.
Factual evidence for the possibility that hydrocarbons may
be formed abiogenically has been available for a long time
in the finding of bitumens in volcanic formations. This is
supported by A. Brun's finding of considerable amounts of
bitumen in many obsidians and in volcanic pumices and
ash. In 1911 D. Edwards drew attention to the fact that
the presence of petroleum bitumens in obsidian had been
established by C. St. Claire Deville even before Brun. In
1930 S. Sacco also found bitumens in obsidians and lavas
of Vesuvius and Stromboli."^
The abiogenic origin of hydrocarbons is also suggested
by a number of gaseous formations which are not directly
associated with sedimentary deposits. Such, for example,
9
130 SIMPLER ORGANIC SUBSTANCES
are the hydrocarbon gases formed in the crystalline forma-
tions of Lake Huron in Canada and in the Ukhta formations
in Karelia where very large amounts of hydrocarbons have
been found in fissures in the volcanic formations. V. Sokolov,
in a personal communication, states that he has found meth-
ane, ethane, propane and higher hydrocarbons in volcanic
formations in a number of places in the Soviet Union.
Of recent years greater and greater numbers of instances
of the presence of petroleum in volcanic and metamorphic
formations have been reported. However, as these finds are
very seldom of economic importance and, in most cases, only
consist of insignificant inclusions, petroleum geologists have
paid very little attention to them. Nevertheless, the finds
of this kind which have already been made in many countries
may be reckoned by hundreds.^"* In particular, liquid and
gaseous hydrocarbons have been found in the form of surface
smears and small quantities of separated material in the
course of deep boring in the fissures of metamorphic and
crystalline formations at levels to which they could hardly
have penetrated from the sedimentary formations.
Thus, although petroleum extracted from sedimentary for-
mations shows clear signs of its biogenic origin, in the light
of the facts now known one cannot deny that even now the
abiogenic formation of hydrocarbons is taking place on the
Earth, albeit to a very limited extent.
Until organisms appeared, these processes were the opera-
tive ones in the formation of hydrocarbons on the Earth as
on the other heavenly bodies. Only after the appearance of
life, when new and higher forms of the motion of matter
came into existence, did there develop new and extremely
highly specialised methods for the transformation of sub-
stances and the utilisation of energy for the synthesis of
organic compounds. In particular, the development of
photosynthesis led to the formation of systems which could
use the inexhaustible source of energy of sunlight for this
process. As a result of this an enormous amount of the
carbon of the surface of the Earth became involved in bio-
logical processes and the old, abiogenic mode of formation
of hydrocarbons lost its significance, as always happens in the
ORIGIN OF EARTH 13I
development of matter ^\ hen a new and more effective form
of motion makes its appearance.
Theory of the origin of the Earth.
Unfortunately, we have, as yet, no single comprehensive
theory as to the way in which the Earth was formed. How-
ever, all the astronomical, geological, physical and chemical
facts bearing on the problem which we can assemble and
all the generalisations w^hich have been made by contempor-
ary cosmogonists of different outlooks conspire to convince
us that large amounts of the simplest organic compounds
must have arisen abiogenically on the Earth at the time of
its formation and during the first period of its existence,
and that these compounds arose by purely chemical, abio-
genic means long before life made its appearance.
As early as the end of the eighteenth century W. Herschel"^
put forward an ingenious idea, which later received the
wholehearted support of Laplace,^"® namely that the stars
and constellations are not something unchanging but that
they arose at various times (and are still arising) and that
they undergo processes of gradual development, the various
stages of which can be observed in the sky.
This idea has been thoroughly substantiated by a number
of astronomical facts which have since been established, in
particular by investigation by V. Ambartsumyan"^ of stellar
associations. These associations seem to be unstable because
the attractive forces between the stars of which they are com-
posed are weaker than those of the galaxy as a whole (espec-
ially the more central parts of it). The stars comprising
these associations are therefore flying apart and, according
to Ambartsumyan's calculations, the associations cannot re-
main in being for long, at most for some tens of millions of
years. Judging from what we can now^ observe of them,
these associations and the stars of which they are composed
have arisen recently. Thus, the process of the formation of
stars is still taking place now. Alongside of this there
occurred, and still occurs, the formation of planetary systems
analogous to our o^vn solar system. The findings of recent
years and, above all, the studies of E. Holmberg"' indicate
that systems of this kind are widely distributed in the uni-
132 SIMPLER ORGANIC SUBSTANCES
verse and that a star with comparatively small cold bodies
circling round it is the rule, rather than a rare exception
as was thought a few years ago. As a result of these studies
there was a withdrawal from the so-called ' catastrophic '
theories of the formation of our planetary system which,
until recently, prevailed among cosmogonists.
According to such theories, and in particular to that of
Sir J. H. Jeans^"® (which was the only theory of the formation
of planets current twenty years ago) the Earth and the other
planets of the solar system arose as the result of an excep-
tional event, a ' catastrophe ', namely the close approach of
another star to our own Sun. As the result of its gravita-
tional attraction, a stream of incandescent gas was drawn
off from the Sun and this provided the material from which
the planets were later formed. This theory came in for devas-
tating criticism at the hands of H. N. RusselP^° who showed
that the theory of the origin of the solar system by collision
between some other star and the Sun was incompatible with
the law of the conservation of momentum.
In 1943 detailed calculations made by N. N. Pariiskii""^
demonstrated completely the incorrectness of Jeans' theory
and later attempts to revive it in one form or another have
not been successful. Furthermore, all the physico-chemical
and geological data disagree with the hypothesis that the
Earth was formed from gases which were originally
incandescent.
Judging by the statements of the cosmogonists, most of
the investigations in this field suggest that our planetary
system is not the result of some very rare, ' happy ' accident
or catastrophe but that it, like many other analogous systems,
arose as a completely normal phenomenon in the course of
the gradual development of matter. According to this hypo-
thesis the material from which the planets were formed was
not provided by incandescent gases but by relatively cold
substances scattered through interstellar space.
Thus contemporary scientific ideas on the origin of the
planets return, in principle, to the hypothesis advanced by
I. Kant"^ more than 200 years ago.
Kant considered that the material which now makes up
the planets did not always constitute a system of isolated
ORIGIN OF EARTH I33
bodies but was scattered throughout the whole of the space
now occupied by the solar system. Under the influence of
gravitational forces the main mass of this material became
aggregated to form a large central body, the Sun. The rest
of the material took the form of a cloud of particles moving
round this body. Their paths crossed one another at all
angles. However, oAving to the reactions bet^veen the par-
ticles, their courses became more and more regular until,
finally, there emerged a flat s^varm of particles revolving
around the Sim, in nearly circular orbits. They approached
one another and joined together to form the ' germs ' of
planets. As these ' germs ' gre^v^ larger they began to attract
particles from more and more distant parts of the swarm
and as this went on the speed of their growth increased
gi'eatly and the ' germs ' turned into planets revolving around
the Sun in circular orbits in the same plane and direction.
This so-called nebular theory of the origin of the solar
system was, at one time, pushed into the background by the
' catastrophic ' hypothesis but came back into currency in
Western Europe and America after the appearance of the
works of C. F. von Weizsacker,"^ D. ter Haar^^^ and S.
Chandrasekhar"'' and in the U.S.S.R. in connection with
the studies of O. Shmidt."^
It is now the ruling hypothesis among cosmogonists, though
it is founded on completely new scientific facts.
In Kant's time nothing Avas known about the nature of
the particles forming the planetary cloud nor about the way
in which they interacted. Astronomers now have at their
disposal very firmly based factual data concerning the chemi-
cal composition of the gases and dust particles which are
collected together in vast clouds in a number of parts of our
galaxy, and also concerning the temperature which prevails
in these clouds, the velocity and size of the particles, the
concentrations of the gas and dust in the various clouds, etc.
Modern theories of cosmogony make use of all these facts,
draw widelv on contemporary physics and chemistry and
apply the principles of thermodynamics and statistical
physics. This makes them more definite and enables them
to give a quantitative description of the phenomena which
are presumed to have occurred. At the same time the
134 SIMPLER ORGANIC SUBSTANCES
demands made on such hypotheses are immeasurably greater.
They must give a rational explanation of all aspects of the
structure of the solar system, the regularity of the orbits,
the distances between the planets, the sizes and masses of the
planets, the peculiarity of the distribution of angular momen-
tum according to which the Sun, in which 99 per cent of
the matter of the solar system is concentrated, nevertheless
has only 2 per cent of the angular momentum of the whole
system and so on. Moreover, a contemporary cosmogonic
hypothesis must not contradict any of the numerous geologi-
cal, physical and chemical facts which are now known.
We have, as yet, no such theory of the formation of the
solar system which can satisfy all these demands. Therefore,
although the overwhelming majority of present-day workers
accept the nebular theory (cf. the review of E. Shatsman"*)
they frequently disagree with one another on such important
questions as the origin and structure of the primaeval cloud
of dust and gas, the mechanism of the formation of aggre-
gates within it, and so forth. For example, O. Shmidt
considered that the planetary cloud was caught up by the
already fully formed Sun ; this happened as it passed through
an accumulation of gas and dust in the course of its motion
round the centre of the galaxy. According to Shmidt this
is the only way in which one can explain the peculiar distri-
bution of momentum within the solar system. On the other
hand, V. Fesenkov"^ maintains that one cannot look at the
problem of the origin of our planetary system in isolation
from the general problem of the origin of stars, and that the
Sun was formed simultaneously or nearly simultaneously
with the planets which surround it and apparently from the
same dust and gases.
In the course of the last ten to fifteen years a number of
observations have been made which establish that the inter-
stellar dust is not uniformly distributed but that there are
separate aggregations of matter of an average extent of two
and a half parsecs though they sometimes attain the colossal
dimensions of 200 parsecs or more. The mass of these clouds
may be 300 times that of the Sun, though B. Bok and E.
Reilly"* also discovered small clouds of cosmic dust which
are easily visible against a luminous background in the shape
ORIGIN OF EARTH
135
of more or less circular spots which are exceptionally im-
permeable to light. These were called ' globules '. The
smallest known globule has a diameter of o-oo6 parsecs and
its mass is 1/500 that of the Sun. Other globules have
considerably greater masses, in some cases several times that
0 BOI B2 BS Ba B9 AO AZ A3 As Fn F2 FS Fa Co GS KO KZ K5 M
■S
.. SPECTRAL CLASS
.j5- ■ -iaooo
■ 3
■ 2
1
0-
.1
-J
■ S- 10
.6 y
.7 S
10
■0
.a ^
■s
.to-
.tr
iuPOC'e'trs
- ■ .f c -■ ' i* i- ; . i
f
-100
-m.
% -"'
.15-
rEMPERAiu^e
-0001
Fig. 10. Hertzsprung-Russell diagram.
of the Sun: i.e. they would be large enough to form one or
several stars. In connection with such a possibility one must
bear in mind the extremely high density of the globules.
This is thousands of times greater than the density of the
interstellar medium which surrounds them.
A theory enjoying considerable popularity among contem-
porary cosmogonists is that one such globule was the ' proto-
star ' from which our planetary system was formed. At some
stage in the development of this globule there arose a central
136 SIMPLER ORGANIC SUBSTANCES
body. When the mass of this body became great enough the
necessary conditions were created within it for the setting
up of the carbon cycle whereby hydrogen is converted into
hehum ; this resulted in the liberation of enormous amounts
of intra-atomic energy so that the body became a star giving
off light, the Sun. The further development of the Sun
proceeded according to the curve of the main sequence in
the Hertzsprung-Russell diagram (Fig. 10).^" The remain-
ing matter of the globule which did not enter into the
constitution of the Sun formed itself into a discoid cloud of
dust and gas from which the protoplanets were formed.
Contemporary cosmogonic literature contains a large
number of hypotheses which try to explain the mechanism of
the formation of planets.
These are based on the rotary motion, gravitational forces
and other physical phenomena which arise when particles of
gas and dust collide.
The motion of the particles in the primaeval planetary
cloud was chaotic. The particles revolved independently
around the central body as very small satellites in different
directions and planes. In the course of their motion they
inevitably collided with each other. However, because the
collisions between the solid particles or between particles of
dust and molecules of gas were inelastic, it follows that as the
kinetic energy was transformed into other forms of energy
the total amount of kinetic energy in the planetary cloud
diminished as time went on. Mathematical analysis of the
development of the planetary cloud under these conditions
shows that this proceeds by the flattening out of the cloud
and the gradual amalgamation of the material which was
originally scattered through space into relatively small bodies
(planetesimals), then into coarser formations made up of
centres in which the material is collected together and finally
into planets.^""
Ways in which organic compounds could
have arisen during the formation of
the Earth.
Most authors devote themselves almost exclusively to the
study of the physical aspects of the subject and try to explain
ORIGIN OF ORGANIC COMPOUNDS I37
the peculiarities of the solar system, which have been men-
tioned abo\e, in this way. In connection with the solution
of the problem of the formation of the first organic com-
pounds, which is our present task, special interest attaches to
the chemical processes which went on during the formation
of the Earth and in the earliest stages of its existence.
The investigations of G. P. Kuiper and the facts put for-
ward by H. C. Urey in his book The planets, their origin and
developtnejit^" are of special value in this connection.
According to Urey the early chemical history of the Earth
and the other planets is determined by the follo^ving basic
factors (cf . Table i ) : —
(1) The distribution of the elements in the cosmos, especi-
ally the composition of the primaeval solar nebula ; (2) the
temperatures which prevailed at the various periods of the
formation of the Earth ; (3) the gravitational field of a planet
in the course of its formation ; (4) the properties of the
chemical substances taking part in this formation.
We may judge of the composition of the primaeval solar
nebula by studying the clouds of dust and gas which exist
at present. The predominant element here, as in the cosmos
in general, is hydrogen. Helium and the other inert gases
are also present, though in considerably smaller quantities.
Such elements as carbon, nitrogen, oxygen, iron, calcium,
silicon, etc., are present in proportions of 1 : 1,000, 1 : 10,000
or even less compared w^ith hydrogen. At the extremely lo\v
temperatures (near to absolute zero) which prevail in a
nebula, only hydrogen, the inert gases and methane can exist
in the gaseous state. Oxygen is present in the form of metallic
(iron) oxides and water, and nitrogen in the form of am-
monia. All these compounds exist in the nebula in the solid
state in the form of fine particles of dust ^\ hich also contain
silicates, metallic iron, iron sulphide, etc.
Urey points out that all the free radicals of carbon, nitro-
gen and oxygen would be transformed into the stable mole-
cules CH4, NH3 and H.o on account of the catalytic action of
the dust and the presence of large amounts of hydrogen in
the nebula. There would also be formed from the free radicals
compounds of high molecular weight characterised by the
linkages c-c, n-n, n-c and c-o.
138
SIMPLER ORGANIC SUBSTANCES
Table i
Time and
Process Occurring
Pliases and
Objects
Chemical
Composition
Temperature
1 . Solar dust cloud.
Gas
Formation of Sun and Dust
disc of gas and dust.
Hj, inert gases, CH^
Silicates, FeO, FeS,
little metallic iron,
solid H,0, NH3.
<^o°C
2. Preprotoplanet and
early protoplanet.
Accumulation of
planetesimals and
substance of the
Moon.
Gas
Dust
H2, inert gases, H^O,
NH„ CH,.
Silicates, FeO, FeS.
Planetesimals
Silicates, FeO, FeS,
hydrated minerals,
NH.Cl, solid H,0
and NH,.
o°C
3. High-temperature
stage. Reduction of
iron oxides. Loss of
gases and volatilised
silicates.
Gas
Hj, inert gases, H,0,
N„ CH,, H,S, vola-
tilised silicates.
Large planetesi-FeO, hydrated min-
mals erals, FeS, NH.Cl,
some metallic iron.
C, Fe,C, TiN.
Small planetesi- Silicates, metallic
mals iron, C, Fe^C, TiN,
some FeS.
2,ooo°C
4. Second low-tem-
perature stage. Final
accumulation of the
Earth.
Gas
Mostly lost. Small
amounts of H^,
H3O, N„ CH,.
HjS, inert gases.
Planetesimals Same as stage 3.
o°C
5. Final stage. Earth Moon
and Moon complete.
Earth
Atmosphere
Silicates, a little metal- Space o°C
lie iron.
45% metallic iron;
55% silicates.
HjO, CH^, Hj,
N,^NH3.
Earth < goo'C
going to
present
temperature
(After Urey, IV. 60, p. 217.)
ORIGIN OF ORGANIC COMPOUNDS 139
After the Sun had become a kiminescent star and the
discoid protoplanetary cloud had been formed, different con-
ditions of temperature were set up in different regions of
the cloud. As a result of the radiations of the Sun the clouds
became warmer till the temperatures at various distances
from the Sun became roughly what they are now.
Urey considers that the combination of particles with one
another which took place during the accumulation of dust
composing the protoplanetary cloud and the formation of
the planetesimals could only have occurred as a result of
the coagulating effect of liquids or damp bodies, as occurs
^\ hen snowballs are made from ^vet snow.
In the formation of the planets water, ammonia and
methane acted as the sticky material. On the basis of his
own calculations Urey determined the distances from the Sun
at which these substances would condense. It seemed that the
condensation of water vapour would occur in the zone
between Jupiter and the asteroids, and that of ammonia in
the neighbourhood of Sattnn but that methane would remain
in the gaseous state right out to the orbit of Pluto. In the
region of the Earth and Venus, however, the condensation of
water and ammonia (especially in the form of nh^oh) might
occur in association \vith local falls in temperature, and this
would create the optimal conditions for the accumulation
of particles of dust here, while in the region of Mars and
the asteroids the crystals of ice were already so dry that they
could not effect coagulation.
The planetesimals which were formed in the neighbour-
hood of the Earth incorporated all the non-volatile substances
of the primaeval cloud of dust, the silicates and their hy-
drates, the oxides and sulphides of iron and other metals,
and also ammonium chloride, water and ammonia. In this
stage in the formation of the protoplanet which was the fore-
runner of the Earth it must already have lost a considerable
amount of hydrogen, helium and neon while ammonia and
the hydrocarbons only escaped partially. Later there occurred
adiabatic compression of the gases of the protoplanet leading
to an increase in the temperature of its central parts, which
rose to nearly 2,000° C.
As the planetesimals passed through the strongly heated
140 SIMPLER ORGANIC SUBSTANCES
gaseous medium their surfaces were heated. In the course
of this heating the oxides of iron and the silicates were
reduced and the latter became gaseous. The gases escaped
and this increased the proportion of iron in the planetesimals.
The smallest ones were completely volatilised, the rather
larger ones were converted into alloys of iron and nickel
while the still larger ones only formed alloys of iron and
nickel on their surfaces, their interiors remaining at low
temperatures and retaining their original composition. At
this stage the ' proto-Earth ' lost a considerable part of its
mass. According to Kuiper, the mass of the Earth at present
is only 1/1,200 part of that of the original protoplanet.
A considerable increase in the proportion of iron in the
Earth resulted fiom this loss of silicates and other volatile
substances. Some water managed to remain on the proto-
Earth in the form of hydrates of silicates and as condensed
water. Nitrogen was retained in the form of metallic nitrides
and salts of ammonia, e.g. ammonium chloride. The most
stable forms in which carbon was retained were carbides of
iron and graphite, for the primaeval hydrocarbons, methane
in particular, must have escaped from the zone in which the
Earth-like planets were being formed. Thus, at the end of
the third postulated (hot) stage in the formation of planets,
large amounts of hydrogen, helium, methane, water and
nitrogen disappeared from the proto-Earth and its further
development proceeded in the absence of any significant
quantities of gas. The temperature of all objects on the proto-
planet therefore fell very quickly by radiation. Thus the
Earth was evidently formed at comparatively low tempera-
tures approaching those of the present day. It was formed
somewhere near to the centre of gravity of the protoplanet
and included in itself all the bodies which moved around
it as satellites.
In this way our planet was accumulated from the planetesi-
mals, which were iron and siliceous bodies similar to the
present-day meteorites. The iron nucleus of the Earth differ-
entiated itself from Tvhat was originally a nearly homogeneous
mass of iron and siliceous phases considerably later, in geo-
logical times. At the same early stage too, the Earth must
certainly have lost those gases, above all hydrogen, which its
ORIGIN OF ORGANIC COMPOUNDS 141
gravitational field could not hold at the temperatures then
prevailing.
In the final fifth stage of the formation of the planet the
primaeval atmosphere of the Earth still kept some remnants
of its original hydrogen, water, ammonia, methane and hydro-
gen sulphide. It was thus highly reducing in character. Only
hydrogen and traces of inert gases were continually escaping
from the atmosphere of the Earth into interplanetary space
while the other gases of the primaeval atmosphere were
almost completely held by the gravitational force of the Earth
at the temperatures then prevailing. The amount of water
on the surface of the Earth at the period under discussion
must have been considerably less than it is now. According
to Urey the total amount of water present on the primaeval
Earth was only lo per cent of that in the present-day oceans.
The rest of the ^vater arose during the development of the
lithosphere, being derived from the hydrates of silicates and,
in general, from the condensed water of the interior of the
Earth. ^^^
In just the same way the amount of methane in the
primaeval atmosphere of the Earth w^as very small because
the greater part of this gas had escaped during the earlier
stages in the development of the planet. As we have seen,
carbon was still present on the Earth in the form of metallic
carbides and graphite. During the formation of the litho-
sphere, however, the carbides reacted with the constitutional
water of the interior of the Earth to form methane and other
hydrocarbons. These separated out from the lithosphere
and accumulated in the atmosphere where they were noAV
retained by the force of gravity. There thus occurred at this
time the same reactions leading to the abiogenic formation
of hydrocarbons which ^ve can even now see taking place
to a small extent.
In just the same way the amount of ammonia in the
primaeval atmosphere of the Earth was constantly augmented
at the expense of ammonium salts and, even more, of nitrides
of metals. The probable formation of nitrides at some period
in the formation of the Earth is supported by the geological
discovery of nitrides of iron in the deep layers of the crust
of the Earth (A. Gautier^") and in volcanic lavas (A. Brun).
142 SIMPLER ORGANIC SUBSTANCES
Goldschmidt has shown that a considerable amount o£ metal-
lic nitrides must also form part of the iron-nickel core of the
Earth. The reaction between metallic nitrides and water
gives rise to ammonia according to the equation
FeN -I- 3H20->Fe(OH)3 -f NHg
Geological findings also point to the presence of ammonium
salts in the lithosphere. V. Vernadskir^^ wrote as follows :
Chlorides and fluorides of ammonium are undoubtedly pro-
duced by volcanoes. These can only be partly attributed to the
destruction of nitrogenous residues of living material carried
away by the lava. Life can in no way be associated with the
production of ammonia together with superheated steam (up
to 190° C) in the neighbourhood of geysers which arise from
depths of no less than 200 metres, such as those in Tuscany in
Italy and Sonoma in California. These gases, of magmatic origin,
are formed simultaneously with the steam.
Ammoniacal aluminosilicates similar to kaolin apparently
exist as isomorphous mixtures of minerals in volcanic and deep
igneous formations, and the derivation of the primaeval nitrogen
from these sources seems very likely.
By analogy with the carbides and nitrides, sulphides of
metals would seem to be the source from which the hydrogen
sulphide of the primaeval atmosphere was formed.
The highly reduced atmosphere which has been described
could not remain unchanged on the Earth for ever. Only if
a planet is very large or the temperature is very low can
it hold all its hydrogen (as happens, for example, on Jupiter
and Saturn). The Earth does not seem to be large enough
for this so, as we have already pointed out, the hydrogen
of its atmosphere was always escaping. However, the ultra-
violet radiation of the Sun was constantly decomposing water
phorochemically in the upper layers of the atmosphere. The
hydrogen arising from these reactions escaped but the oxygen
oxidised ammonia to molecular nitrogen and converted the
primitive Hydrocarbons into various oxygen-containing or-
ganic compounds such as alcohols, aldehydes, ketones and
acids ; carbon monoxide and carbon dioxide appeared as
the final products of this oxidation, and it was from these
ORIGIN OF ORGANIC COMPOUNDS 143
that the first carbonates were formed. At the same time
direct photochemical changes of methane and ammonia were
going on, for both of them absorb ultraviolet light, methane
at a wavelength below 1,450 A and ammonia at a wavelength
below 2,250 A. Under these conditions methane forms hydro-
gen, higher saturated hydrocarbons and unsaturated hydro-
carbons, particularly ethylene. The ethylene thus formed
can be converted photochemically into acetylene and a whole
series of liquid hydrocarbons. Ammonia is decomposed
photochemically into NH2 -f h with the formation of hydrazine
NH2NH2 and other nitrogenous substances. The radicals which
were thus formed in the primitive atmosphere of the Earth
such as — CH3, ^CH2, =CH, — NH2, ^NH, and — oh reacted
with one another, giving rise to a large number of different
sorts of organic compounds, the simplest oxygen- and
nitrogen-containing derivatives of hydrocarbons.^^*
The oxygen which was produced by the photolysis of water
must have reacted not only Avith ammonia and hydrocarbons
but also with other reduced substances, for example by
oxidising hydrogen sulphide and metals, particularly iron.
Thus, in spite of the continued photolysis of water and escape
of hydrogen, free oxygen did not appear in the atmosphere
of the Earth in significant amounts for a long time.
On the basis of a study of the distribution of the isotopes
of sulphur in its oxidised and reduced compounds H. G.
Thode and colleagues^^^ reached the conclusion that the
original transition of the atmosphere of the Earth from the
reduced to the oxidised state occurred only 700 or 800 million
years ago, that is to say, at a time when, according to all the
evidence, life already existed on the Earth and photosynthesis
may even have begun.
On the basis of a study of the abundances of isotopes of
lead and other elements various authors have given estimates
of the age of the Earth ranging from 3-4 to 5.3 x 10^
years. ^^®'^^'' It follows that for at least 2-3 x 10^ years the
atmosphere of the Earth was reduced, or undergoing gradual
transition to the oxidised state, and that under these condi-
tions there occurred on the surface of the Earth the abiogenic
formation first of the simplest and later of more complicated
organic compounds.
144 SIMPLER ORGANIC SUBSTANCES
As we shall see later, this primitive way of carrying out
organic syntheses abiogenically was very ineffectual, it
was slow and circuitous. It occupied thousands of millions
of years. This was the first and most primitive epoch of
purely chemical synthesis of organic substances on the Earth
and it extended throughout the greater part of the history
of the planet. It is only 700 or 800 x 10® years since a new
and far more efficient method of synthesis of organic ma-
terials, photosynthesis, was elaborated on the Earth on the
basis of the emergence and later development of a new form
of the motion of matter, namely life. This process made use
of the enormous resources of energy of the sunlight, and the
actual synthesis was not haphazard as it had been before
but was carried out by the extremely highly-organised succes-
sion of events which we call biological metabolism. As always
occins in the history of the development of matter, this new
and efficient method, once it had developed, superseded the
old inefficient way of synthesising organic substances abio-
genically so that now it is only with difficulty that we can
discover even the slightest manifestations of it.
We are now living in the second, biological, epoch of the
history of our planet in which green plants almost mono-
polise the synthesis of organic substances.
When man began to practise cultivation, he achieved great
progress in making plants produce larger and larger amounts
of organic substances. However, all this progress, which has
been extremely important in human history, occurred within
the framework of what we have called the second epoch, that
of biological synthesis of organic substances. It is all based
on the formation of such substances by the green leaf using
the energy of sunlight.
The contemporary development of science, however, justi-
fies the belief that we are on the threshold of a new, third,
epoch in the history of our planet. The control of nuclear
energy opens up to mankind the possibility of using this
energy to synthesise organic substances directly from carbon
dioxide at any place or time, independently of the season or
the weather and without having to use enormous areas of
the surface of the Earth and other resources.
In principle this new way of synthesising organic com-
BIBLIOGRAPHY I45
pounds is a great improvement on the biological method,
just as the speed of aeroplanes at present is an improvement
on that of the earlier horse-drawn carriages of the time of
Dickens.
However, this new and efficient method of synthesis of
organic substances can only arise on the basis of a tremendous
development in human society ; on the basis of new social
forms which are far higher and more efficient than the bio-
logical ones. It will therefore gradually supersede the old
method of photosynthesis which now seems efficient and even
the only possible method. Certainly this is still only a dream,
but it is already a dream with a scientific foundation and it
shoAvs ^vhat tremendous vistas of a cosmic nature are opening
out before mankind as the result of a wise and progressive
use of the achievements of science.
BIBLIOGRAPHY TO CHAPTER IV
1. C. Sterne. Entivicklung der Erde und des Kosmos, der Pfian-
zen und der wirbellosen Tiere. Leipzig, 1905.
2. J. J. Berzelius. Lehrhuch der Chemie (Ubers. K. A. Blode
und K. Palmstedt). Vol. 3. Dresden, 1827.
3. F. WoHLER. Ann. Phys., Lpz., 12, 253 (1828).
4. Quoted by E. Hjelt. Geschichte der organische Chemie von
dltester Zeit bis zum Gegenwart. Braunschweig, 1916.
A. Arbuzov. Kratkii ocherk razvitiya organischeskoi khimii v
Rossii. Moscow and Leningrad (Izd. AN SSSR), 1948.
5. A. Bernthsen. Kurzes Lehrbuch der organische Chemie (8
Aufl.). Braunschweig, 1902.
P. Karrer. Lehrbuch der organischen Chemie (4 Aufl.).
Leipzig, 1936.
6. C. Schorlemmer. The rise and development of organic
chemistry. (Revised edition.) London, 1894.
7. A. Chichibabin. Osnovnye nachala organicheskoi khimii.
Moscow (Goskhimizdat), 1954.
8. K. Timiryazev. Sochineniya. Vol. 4, p. 161. Moscow (Sel'-
khozgiz), 1938.
9. S. WiNOGRADSKY. Bot. Ztg, 4^, 489, 606 (1887) ; 46, 262
(1888).
10. S. ViNOGRADSKii. O roH mikrobov v obshchem krugovorote
zhizni. Address to General Assembly of Members
of Imperial Institute of Experimental Medicine
(8/12/1896). St. Petersburg, 1897.
10
146 SIMPLER ORGANIC SUBSTANCES
11. J. LiEBiG. Die organische Chemie in ihrer Anwendung auf
Agricultur und Physiologie. Braunschweig, 1840.
12. E. I. Rabinowitch. Photosynthesis and related processes.
New York, 1944, 1951, 1955.
Yu. I. SoROKiN. Personal communication about work at
scientific research station ' Borok '.
13. H. PoTONiE. Die Entstehung der Steinkohle und der Kausto-
hiolithe iiberhaiipt. Berlin, 1920.
Yu. Zhemchuzhnikov. Obshchaya geologiya iskopaemykh
uglei. (2nd edn.) Moscow (Ugletekhizdat), 1948.
14. M. Berthelot. Bull. Sac. chim. Paris, 11, 278 (1869).
15. D. Mendeleev. Neftyanaya promyshlennost' v Sev. Ameri-
kanskom shtate Pensil'vanii i na Kavkaze. St. Peters-
burg (Izd. ' Obshchestvennaya Pol'za '), 1877.
16. C. Engler and H. H. v. Heimhalt (ed.). Das Erdol Bd. 1.
Leipzig, 1913.
17. A. D. Arkhangel'skii. Usloviya obrazovaniya nefti na
Severnom Kavkaze (seriya Neftyanoe Khozyaistvo).
Moscow, 1927.
18. V. I. Vernadskii. Ocherki geokhimii. Moscow (Gosgorgeonef-
tizdat), 1934.
19. N. D. Zelinskii. In the Jubilee Volume: Akademiku V. I.
Vernadskomu k ^o-letiyu nauchnoi i pedagogicheskoi
deyatel'nosti (ed. A. P. Karpinskii and A. E. Fers-
man), p. 875. Moscow and Leningrad (Izd. AN SSSR),
1936.
20. G. Stadnikov. Proiskhozhdenie uglet i nefti. Moscow and
Leningi-ad (Izd. AN SSSR), 1937.
21.1. GuBKiN. Uchenie o nefti. Moscow and Leningrad (ONTI),
1937-
2Z. H. Craig. Geochim. et Cosmochim. Acta, ^, 53 (1953).
23. (III. 22).
24. (III. 23).
25. (III. 24).
26. (III. 13).
27. (III. 14).
28. V. Omelyanskii. Osnovy mikrobiologii. Petrograd (Gosiz-
dat), 1922.
29. (III. 15).
30. (11. 5).
31. V. KoMAROV. Proiskhozhdenie rastenii. Moscow and Lenin-
grad (Izd. AN SSSR), 1936.
BIBLIOGRAPHY I47
32. D. D. Woods and J. Lascelles in Autotrophic micro-organ-
isms (ed. B. A. Fry and J. L. Peel), p. 1. Cambridge,
1954-
33. A. Pascher. Flagellate?! und Rhizopoden in ihren gegen-
seitigen Beziehungen. Jena, 1917.
34. C. H. Werkman and H. G. Wood. Advanc. Enzymol., 2, 135
(1942)-
35. M. Stephenson. Bacterial metabolism (3rd edn.). London,
1949-
36. W. O. Kermack and H. Lees. Science Progr., 40, 44 (1952).
37. A. Lebedev. Issledovayiie khemosinteza u Bacillus hydro-
genes. Odessa (Tip. Shtaba Okruga), 1910.
W. RuHLAND. Jb. wiss. Bat., 6}, 321 (1924).
38. K. G. Vogler. /. gen. Physiol., 2^, 617 (1942).
39. W. W. Umbreit. Bact. Revs., 11, 157 (1947).
40. Yu. I. Sorokin. Mikrobiologiya, 2^, 363 (1956).
41. V. Dogel'. Obshchaya protistologiya. Moscow (Izd. ' Sov.
Nauka '), 1951.
42. L. KuRSANOv, N. KoMARNiTSKii, K. Meier, V. Razdorskii
and A. Uranov. Botanika, Vol. 2. Moscow (Izd. ' Sov.
Nauka '), 1951.
43. A. LwoFF (ed.). Biochemistry and physiology of Protozoa.
Vol. 1. New York, 1951.
44. A. Elenkin. Notul. syst. Inst, cryptog. Horti hot. petropol.,
3' 171 (1924)-
45. A. Zakhvatkin. SravjiiteVnaya embriologiya nizshikh bespoz-
vonochnykh. Moscow (Izd. ' Sov. Nauka '), 1949.
46. A. Markevich. Problema proiskhozhdeniya prosteishikh
Protozoa. Kiev (Izd. Kiev Univ.), 1954.
47. A. I. Oparin. Communication to meeting of Russian Botani-
cal Society. Moscow, 1922.
48. H. A. Bethe. Phys. Rev., 55, 434 (1939) ; Nature (Lond.),
143,904 (1939).
49. J. S. Plaskett. Publ. Dom. astrophys. Obs., Ottawa, 2, no. 16,
287 (1924).
50. F. Henroteau and J. P. Henderson. Publ. Dom. Obs.,
Ottaiva, ^, no. 1, p. 1 (1920).
F. Henroteau. Publ. Dom. Obs., Ottaiva, ^, no. 8, p. 331
(1922).
51. E. P. Waterman. Lick Obs. Bull., 8, no. 243, p. i (1913)-
52. W. C. RuFUS. Publ. astr. Obs. Univ. Mich., 2, 103 (1916).
R. F. Sanford. Publ. astr. Soc. Pacif., 41, 271 (1929).
148 SIMPLER ORGANIC SUBSTANCES
53. G. Shain. Vestnik Akad. Nauk S.S.S.R., no. 10, p. 52 (1940).
G. A. Shain and V. F. Gaze. Doklady Akad. Nauk S.S.S.R.,
68, 661 (1949).
A. Daudin and C. Fehrenbach. C.R. Acad. Sci., Paris, 222,
1083 (1946).
54. H. V. Kluber. Das Vorkommen der chemischen Elemente
im Kosmos. Leipzig, 1931.
55. O. Struve. /. Wash. Acad. Sci.,^i,2iJ (1941).
V. G. Fesenkov. Meteornaya materiya v mezhplanetnom
prostranstve. Moscow and Leningrad (Izd. AN SSSR),
1947-
G. A. Shain and V. F. Gaze (Shajn and Gase). Trans, int.
astr. Un., 8, 693 (1952).
56. L. Spitzer and M. P. Savedoff. Astrophys. J., in, 593
(1950).
57. L. GuREViCH. In Voprosy kosmogonii (ed. B. V. Kukarkin).
Vol. 3, p. 94. Moscow (Izd. AN SSSR), 1954.
58. V. Sofronov. Review in Voprosy kosmogonii (ed. B. V.
Kukarkin). Vol. 2, p. 275. Moscow (Izd. AN SSSR),
1954-
59. H. Kramers and D. ter Haar. Bull. astr. Insts Netherlds,
10, 137 (1946).
60. H. C. Urey. The planets, their origin and development.
New Haven, Conn., 1952.
61. D. R. Bates and L. Spitzer. Astrophys. J., 11^, 441 (1951).
62. H. N. Russell. The solar system and its origin. New York,
1935-
63. G. P. KuiPER (ed.) The atmospheres of the Earth and planets
(revised edition). Chicago, 1952.
64. A. Adel and V. M. Slipher. Phys. Rev., 46, 902 (1934).
65. G. P. KuiPER. Astrophys. J., 100, 378 (1944).
66. F. W. Clarke. Prof. Pap. U.S. geol. Surv., i^2D, 51 (1924).
67. H. S. Washington. Amer. J. Sci. (ser. 5), p, 351 (1925).
68. V. M. GoLDSCHMiDT. Gcochemische Verteilungsgesetze der
Elemente. Oslo, 1938.
69. I. NoDDACK and W. Noddack. Natunoiss., 18, 757 (1930).
70. A. Fersman. Geokhimiya. Vols. 1 and 2. Moscow (ONTI),
1934-
71. H. Brown and C. Patterson. /. Geol., ^^, 405 (1947).
72. H. C. Urey and H. Craig. Geochim. et Cosmochim. Acta,
4> 36 (1953)-
73. P. N. ChirvinskiI. Meteoritika,io,6'j(iQP,2).
74. S. Orlov. Vestnik Moskov. Univ. Ser. Fiz.-Mat. i Estestven.
Nauk, II, 43 (1949).
BIBLIOGRAPHY 149
75. V. G. Fesenkov. Meteoritika, 8, 38 (1950).
76. A. N. Zavaritskii. Meteoritika, 8, 100 (ig^o).
77. R.A.Daly. Bull. geol. Soc. Amer., ^^, 401 (ig^^).
78. B. Yu. Levin. Meteoritika, 11, 47 (1954) ; Sborjiik voprosy
vniLtrennogo stroeniya i rasvitiya Zemli (ed. V. V.
Belousov), p. II. Moscow (Izd. AN SSSR), 1955.
79. I. AsTAPOvicH and V. Fedynskii. Meteory. Moscow and
Leningrad (Izd. AN SSSR), 1940.
80. L. G. KvASHA. Meteoritika, ^,8^ (ig4-S).
8i. A. V. Trofimov. Meteoritika, 8, 12"] (ic^P^o).
82. Quoted in (IV. 54, p. 54).
82=^. F. WoHLER. S.B. Akad. Wiss. Wien,^^, 205 ; 34, 7 (1859).
83. P. G. Melikov and V. Krshizhaxovskii. Amu. geol. min.
Russ., 2 (Otd. 3), p. 109 (1897) ; /• ■^O'^- phys.-chim.
russe, 28 (Chem.), 651 (1896).
84. J. L. Smith. Original researches in mineralogy and chemistry.
Louisville, Ky., 1884 ; (II. 23).
85. F. L. Whipple. Astrophys. J., iii, 375 (1950).
86. O. Shmidt. Trudy geofizicheskogo Instituta A.N. S.S.S.R., 26,
5 (1955)-
87. V. LoDOCHNiKOV. Zapiski Vserossilskogo Mineralog. Obsh-
chestva (Ser. 2), Part 68 (no. 2), 207 (1939).
88. G. Forchhammer. Overs, danske Vidensk. Selsk. Forh., i, i
(1854).
89. M. Neumayr. Erdgeschichte (2 AuH.). Leipzig, 1895.
90. (J.) L. Smith. Ann. Chim. (Phys.), (Ser. 5), 16, 452 (1879).
91. R. T. Chamberlin. Publ. Carneg. Instn, no. 106 (1908).
92. V. Vernadskii. Ocherki geokhimii. Moscow (Gorgeonefteiz-
dat), 1934.
93- (IV. 14).
94. H. Abich. ]b. geol. Reichsanst., Wien, 2p, 177 (1879).
95. H. MoissAN. C.R. Acad. Sci., Paris, 122, 1462 (1896).
96. D. Mendeleev. Osnovy khimii. Vol. 1, p. 379. Moscow and
LeningTad (Gosizdat), 1927.
97. Proiskhozhdenie nefti (ed. M. F. Mirchink, A. A. Bakirov,
B. F. D'yakov and D. V. Zhabrev). Moscow (Gos.
Nauch. Tekh. Izd. neft. i gorn. topi. Lit.), 1955.
98. H. Hahn. Liebigs Ann., 12^, 57 (1864).
99. S. Cloez. C.R. Acad. Sci., Paris, 86, 1248 (1878).
100. K. V. Kharichkov. /. Soc. phys.-chem. russ., 28 (Chem.), 825
(1896) ; 29 (Chem.), 151 (1897).
101. V. Ipat'ev. Neft' i ee proiskhozhdenie. St. Petersburg
(Izdatel'stvo A. Panafidinoi), 1914.
50 SIMPLER ORGANIC SUBSTANCES
02. (III. 6l).
03. N. KuDRYAVTSEV. Nejijanoe Khoz., g, 17 (1951)-
04. P. Kropotkin. In Sovetskaya geologiya, Part 47, p. 104.
Moscow (Gos. nauch. tekh. Izd. vo Geol. Okhrani
Nedr), 1955.
05. W. Herschel. Quoted by A. Berry. A short history of
astronomy. London, i8g8.
06. P. S. Laplace. Exposition clu systeme du monde. Paris,
1796.
07. V. Ambartsumyan (Ambartsumian). Trans, int. astr. Un.,
S, 665 (1952).
08. (II. 13).
09. J. H. Jeans. Astronomy and cosmogony. Cambridge, 1928.
10. (IV. 62).
loa. N. N. Pariiskii. Astron. Zhur., 20, 9 (1943) ; 21, 69 (1944).
11. I. Kant. Allgemeine Naturgeschichte und Theorie des
Himmels. Konigsberg, 1755.
12. C. F. V. Weizsacker. Z. Astrophys., 22, 319 (1944).
13. D. TER Haar. Rev. mod. Phys., 22, 1 19 (1950).
14. S. Chandrasekhar. Rev. mod. Phys., 18, 94 (1946) ; hitro-
duction to the study of stellar structure. Chicago,
1939-
15. O. Shmidt. Chetyre lektsii o teorii proiskhozhdeniya Zemli.
Moscow (Izd. AN SSSR), 1950.
16. E. Shatsman. In Voprosy kosmogonii (ed. B. V. Kukarkin).
Vol. 3, p. 227. Moscow (Izd. AN SSSR), 1954.
17. V. Fesenkov. In Trudy i-go soveshchaniya po voprosam
kosmogonii, p. 35. Moscow (Izd. AN SSSR), 1951.
18. B. J. BoK and E. F. Reilly. Astrophys. J., 10^, 255 (1947).
19. O. Struve. Stellar evolution : an exploration from the
observatory. Princeton, N.J., 1950.
120. L. Gurevich and A. Lebedinskii. Izvest. Akad. Nauk
S.S.S.R. Ser. Fiz., 14, 765 (1950) ; Astron. Zhur., 2'],
273 (1950) ; also in Voprosy kosmogonii (ed. B. V.
Kukarkin), Vols. 2 and 3. Moscow (Izd. AN SSSR),
1954-
G. Khil'mi. 200 let nauchnoi kosmogonii. Moscow (Izd.
* Znanie '), 1955.
121. W. W. Rubey. Bull. geol. Soc. Amer., 62, WW (^i^^i).
122. A. Gautier. Ann. Min., Paris, (ser. 10), p^ 316 (1906).
123. (IV. 92).
BIBLIOGRAPHY 151
124. W. A. NoYES (jr.) and P. A. Leighton. The photochemistry
of gases. New York, 194 1 .
G. K. RoLLEFSON and M. Burton. Photochemistry and the
mechanism of chemical reactions. New York, 1939.
125. A. SzABO, A. TuDGE, A. Macnamara, and H. G. Thode.
Science, iii, 464 (1950).
126. A.Holmes. Rep. Smithson. histn, i^^8, p. 22"].
127. F. F. KoczY. Nature, Lond., i^i, 24 (1943).
CHAPTER V
ABIOGENIC ORGANIC-CHEMICAL
EVOLUTION OF CARBON COMPOUNDS
Thermodynamics and kinetics of the transformation
of the simplest hydrocarbons in the lithosphere,
atmosphere and hydrosphere of the Earth.
As was pointed out at the end of Chapter IV, the Earth,
during a considerable period of its existence, was devoid of
Hfe. During a substantial part of this time, those many
millions of years which separate the time of the formation
of the Earth from the appearance of life on it, there took
place the abiogenic, organic-chemical evolution of carbon
compounds. Hydrocarbons and their simplest nitrogen- and
oxygen-containing derivatives began to be found on the
surface of the Earth, as has been shown above, at the very
earliest stage of its existence. However, these compounds
were only the starting point, the first link in a long chain of
diverse organic-chemical reactions which now began and
Avhich led to the formation in the atmosphere and the hydro-
sphere of the Earth of a large number of varied compounds,
some of which were of complicated structure and high mole-
cular weight, similar to the substances entering into the
composition of present-day animals and plants.
The basic requirements for this second stage of the
development of matter from the simplest hydrocarbons to
the most complicated organic compounds were inherent in
the original hydrocarbons themselves. Hydrocarbons possess
enormous chemical potentialities. It is with good reason
that the whole of organic chemistry is today regarded as the
chemistry of hydrocarbon derivatives. The diagram (Fig.
ii),^ showing the free energies of formation of organic com-
pounds, demonstrates clearly the thermodynamic possibility
of the passage from hydrocarbons to their oxygen- and
nitrogen-containing derivatives. Polymerisation and con-
densation of these derivatives could then give rise to more
J53
154 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
60,000
50,000
40,000
30,000
20,000
10,000
0
- 10,000
o -20,000
^ -50,000
ol -40,000
U-
- 50,000
OIPHEf^n
ACETYLENE
PROPrNE
NAPHTHALENE,^
BENZENE^-r^QlUefil ••'TZ. "
£A/i^
craoPROPANE ^-scr '^ .;jgS
craoPENrANE^.. .-Jii-* — y^p^i^^^ ^•*
CrCLOHEXANE^ • -
/'
.^•^.•;r;^^'"" .
BENZYL ALCOHOL
PHENOL
METHANE
- 60,000
- 70,000
- 80,000
- 90,000
-100,000
-110,000
Fig.
BENZOQUINONE .,
N^ \^^YD£^ ^CrCLOHEXANOL
• — Xlcohols
'UREA
, HYDROQUINONE
• RESORCINOL
' PYROCATECHOL
• BENZO/C AC/D
GLYCOL
•
\ GLYCEROL
'
I Z 5 4 5 6 7 8 9 10 II 12 13
NUMBER OF CARBON ATOMS IN THE MOLECULE
11. Diagram of the free energy of organic
compounds.
TRANSFORMATION OF HYDROCARBONS 155
and more complicated organic compounds on the surface of
the Earth when it was still devoid of life. But when one
proceeds beyond asserting in principle the possibility of
organic-chemical evolution, it is indeed a difficult task to
trace the actual paths along which such evolution proceeded
during that remote epoch when the Earth was uninhabited
by living organisms.
At first sight it might seem that a simple and reliable
approach to solving this problem would be through geologi-
cal and, especially, geochemical study. One could observe,
under natural conditions, the changes which carbon com-
pounds today undergo on the surface of the Earth in the
absence of living matter, and make detailed chemical study
of these changes. Such investigations could, indeed, give
valuable results in the long run. However, it must be
remembered that the emergence of life and, especially, of
photosynthesis, has markedly changed all the conditions
which exist on the surface of the Earth. At the present time,
under natm^al conditions, we cannot directly observe many
of those phenomena which manifested themselves in the past.
Moreover, new processes have now appeared which were
absent from the surface of the Earth when it was devoid of
life. Consequently we should be wrong to apply, in a simple
and mechanical fashion, the data of contemporary geo-
chemistry to the remote early period of the existence of the
Earth. We cannot use these data as they stand but must
amend them by making free use of laboratory experiments
in the attempt to reproduce artificially the various conditions
which have been postulated as occurring on the primaeval
Earth. We must then investigate the transformation which
organic substances undergo when they are exposed to these
conditions.
As was pointed out in the previous chapter, the picture of
the formation of the Earth which is at present favoured by
scientists is that it took place at comparatively low tempera-
tures, of the same order as those at present prevailing here.
Even from the earliest period of its existence, the Earth had
a firm surface, an aqueous envelope (the hydrosphere) and a
gaseous envelope (the atmosphere). The temperature of the
firm surface will have depended very much on the radio-
156 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
active decay of the actinouranium and of one of the isotopes
of potassium present there ; later on, it will have been
determined more by that of uranium and thorium. In con-
sequence of this, the interior of the Earth became heated,
reaching at some points temperatures of the order of 1,000° C
or more. At the high pressures which also prevailed, there
resulted a redistribution of the substances present — the
heavier aggregates, rich in iron, sank inwards, while those
that were lighter (silicates) floated towards the surface. This
led to the formation of the crust of the Earth, the lithosphere,
as a result of the lighter rock formations being squeezed out
in a molten state on to the surface of the planet. This process
continued throughout geological time and cannot even now
be regarded as at an end.
Intimately linked with the formation of the lithosphere
is the development of the hydrosphere and of the primaeval
atmosphere of the Earth. ^ The amount of water present on
the surface of the Earth was much less than that now present.
This was gradually increased by the decomposition of hy-
drates and the liberation of water of constitution from the
interior of the Earth.''*
The hydrosphere was also markedly different in its chemi-
cal composition. The waters of the primitive seas and oceans
were poorer in inorganic salts than are their present-day
counterparts. The migration of the elements which make up
these salts only proceeded rather slowly, chiefly as a result of
the natural circulation of water. This migration was a very
important preliminary stage in the development of life.
The temperature both of the hydrosphere and of the atmo-
sphere was largely determined by the radiation reaching the
Earth from the Sun. The strength of this seems scarcely to
have changed during the whole period in which the Earth
has existed.
The principal qualitative difference from present-day con-
ditions was in the composition of the primaeval atmosphere.
The atmosphere to-day has an oxidising character, being very
rich in free molecular oxygen. But the overwhelming bulk
of this gas was formed, and continues to be formed, bio-
genically, as a result of the activity of green plants. The total
amount of oxygen in the present-day terrestrial atmosphere
TRANSFORMATION OF HYDROCARBONS 157
may be taken to be about 2-8 x lo^"* tons. According to
calculations of E. Rabinowitch,^ the entire vegetation of the
globe produces by photosynthesis i-2 x lo" tons of oxygen in
the course of one year. It follows that the entire amount of free
oxygen in the atmosphere could be produced by vegetation
in roughly 2,000 years — a period which is completely insigni-
ficant in relation to the thousands of millions of years during
which the Earth has existed. As early as 1856 C. Koene*^ put
forward the theory that the entire oxygen of the atmosphere
owes its origin to photosynthesis by green plants. This
idea was supported by many later authorities. It was, how-
ever, handled in a specially detailed way by V. Vernadskii."
Basing his arguments on a whole series of geochemical facts,
Vernadskii demonstrated the biogenic origin of the oxygen
in the present-day atmosphere.
There is also, in the scientific literature, considerable dis-
cussion of the possibility of formation of molecular oxygen
by an inorganic mechanism. In particular, G. Tammann*
and, later, R. Wildt^ pointed out that a certain amount of
oxygen might have been formed by thermal dissociation of
water. This theory was not, however, sufficiently soimdly
based, and has met with serious opposition from the majority
of geologists and chemists. In any case, such oxygen as might
have been formed in this fashion would immediately have
been absorbed by mineral formations which were unsatur-
ated in respect of this element.
There is much more in favour of the view that water
undergoes photolysis in the uppermost layers of the
atmosphere under the influence of ultraviolet radiation. S.
Arrhenius" discussed this possibility, and it has since been
considered by V. M. Goldschmidt,^^ W. Groth and H. Suess,^'
J. H. J. Poole,^' N. R. Dhar^-* and others.
According to G. Rathenau,^^ water vapour absorbs in the
ultraviolet at wavelengths 1,780 A, 1,540 A and 1,340 A
(according to R. Mecke,^^ 1.390 A). As early as 1910 A.
Coehn^^ described the direct photochemical decomposition
of water into hydrogen and oxygen on ultraviolet irradiation
of water vapour. The equation is :
light
H2O + H2O > 2H2 -I- Oo
158 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
Later, the ultraviolet photolysis of water under a variety
of conditions was observed by A. Tian," H. Neuimin and
A. Terenin/^ and by several other workers.
P. Harteck and J. H. D. Jensen^" tried to calculate the
total quantity of oxygen which might have been formed
photochemically in the upper layers of the atmosphere during
the entire period of existence of the Earth (which they
estimated as 3 x 10^ years) if hydrogen had been constantly
escaping into space. The calculated quantity of oxygen was
many tens of times that now present in the atmosphere. If
this were so, such extensive abiogenic photochemical produc-
tion of oxygen would speak against the idea that atmospheric
oxygen owes its origin exclusively to photosynthesis by plants.
However, later determinations of the content of water
vapour in the cold upper layers of the atmosphere, particu-
larly those by G. M. B. Dobson,^^ failed to confirm the cal-
culations of Harteck and Jensen. The results of H. E. Moses
and Ta-You Wu^^ on the recombination of oxygen with
hydrogen were also in conflict with them. Thus, it appears
that, during the entire period of existence of the Earth, there
could not have been formed by inorganic, abiogenic means
a quantity of free oxygen vastly exceeding that present in
the atmosphere of to-day.
Reducing conditions.
It follows that it was the emergence of life itself and the
appearance of biogenic photosynthesis which established on
the surface of the Earth the markedly oxidising conditions
under which we now live. Up till this time reducing condi-
tions prevailed on the lifeless Earth, under which oxygen
can only be supposed to have occurred in the combined state,
in the form of water, metallic oxides, silicates, alumino-
silicates, etc. The following compounds were of special im-
portance": FeaSlOa, MgSiOg, Ca3(Al03) a-H-.O, Ai(oh)3. At the
same time substantial amounts of metals and other substances
existed, in whole or in part, in the reduced state, since no
oxygen was available for combination with them.
The comparatively small amounts of free oxygen formed
by the photolysis of water in the upper layers of the atmo-
REDUCING CONDITIONS 159
sphere were now taken up by incompletely oxidised sub-
stances. This completely prevented any accumulation of
oxygen in the atmosphere of the Earth before life had
appeared. Even now, when the reserves of free oxygen in
the atmosphere are continually being replenished by green
plants, it is only the outermost skin of the crust of the
Earth which is oxidised. The deeper formations remained in a
strongly reduced state, combining avidly with oxygen. This
may be illustrated by the well-known fact that lava and basalt
are black, green and grey, showing that they contain iron
in an incompletely oxidised state. The sedimentary forma-
tions such as clays and sands, on the other hand, are red or
yello^v in colour. In these the iron is fully oxidised. Thus,
oxygen is gradually being taken up before our very eyes in
the transformation of igneous into sedimentary formations
and it is only the process of photosynthesis which continually
replenishes the atmosphere ^vith this gas. According to the
calculations of V. M. Goldschmidt,^^ if all the plants on the
Earth were suddenly destroyed the free oxygen of the atmo-
sphere would disappear within a iew thousands of years,
a very short time on the geological scale ; it would be taken
up by incompletely oxidised minerals.
However, even in such a case, the Earth, though bereft of
life, would not return to its original state. The oxidised
conditions brought into being by life would leave indelible
traces on its surface in the shape of oxidised rock formations.
This applies particularly to carbon compounds. Under the
reduced conditions prevailing on the primaeval Earth carbon
existed mainly in the form of carbides, graphite and hydro-
carbons.
The appearance of free oxygen created the conditions
under which hydrocarbons could be oxidised. The final stage
in this process was the formation of carbon dioxide, but this
could not accumulate in significant amounts in the atmo-
sphere because it reacted with the silicates of the lithosphere
and was held there as carbonates" in accordance with such
an equation as MgSiOo, + cOo->MgC03 + siOo.
The process of the formation of carbonates was greatly
intensified after the appearance of life, and the crust of the
Earth now contains enormous deposits of carbonate-contain-
l6o ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
ing formations which serve to replenish the atmosphere with
carbon dioxide during all sorts of plutonic processes. It is
for this reason that the only carbon compound which is
present in quantitatively significant amounts in volcanic
gases and the volatile constituents of magma is CO2, while
hydrocarbons are present sometimes, but only as traces. It
was on the basis of such observations that many authors
(e.g."*") who had not taken into account the difference
between the conditions formerly present on the surface of
the Earth and those which now prevail, accepted carbon
dioxide as the primary compound from which all further
organic evolution proceeded. For example, H. Borchert^*
referred directly, in his discussion of the matter, to the com-
position of the volcanic gases of the Hawaiian islands and
also to the considerable preponderance of CO2 over co and
CH4 in the gases which emerge from the inside of the Earth
in molten formations and, when these crystallise, become part
of the atmosphere.
But V. Vernadskir" in his Outlines of geochemistry had
already pointed out that the carbon dioxide which is formed
in enormous amounts at times of volcanic eruption and in
quiescent volcanic areas is ' juvenile ' only in the sense that
it originates from ' juvenile ' regions (deep layers of the crust
of the Earth or magmatic foci). Its appearance is, however,
due to the decomposition of previously formed carbonates,
which is brought about at the high temperatures of the deep
layers of the crust of the Earth and through the melting of
metamorphic formations (Fig. 12).
Urey^° was also quite right when, in criticising Poole, he
pointed out that one cannot understand how carbon dioxide
could have been formed from the graphite, methane or car-
bides of the interior of the Earth under the reducing condi-
tions which existed on the primaeval Earth.
Only by ignoring the changes which have come about on
the surface of the Earth since it became inhabited by organ-
isms, by mechanically transferring present conditions to the
remote past, can one explain the fact that many authors
writing on the subject of the origin of life based their argu-
ments on the assumption that carbon dioxide was the primary
compound of carbon. As a result of this they met with
SOURCES OF ENERGY
l6l
unnecessary difficulties sucli as tfie need to discover tfie con-
ditions under which a completely oxidised compound (cOo)
could be converted into organic compounds of high energy.
These investigators devoted the greater part of their attention
to resolving these problems although what they should, in
fact, have explained first was how carbon dioxide itself could
arise under the conditions present on the primaeval Earth.
BIOSPHERE
LIVING MATTER
SEDIMENTARY
LAYERS
CARBONATES
I
CARBONATES
CARBONATES
PETROLEUM S\
JUVENILE CH
LAYERS
\'
METALLIC
CARBIDES
COALS
\
NATIVE CARBON
GRAPHITES
/
LIVING
MATTER
CARBONATES
c
CO,
CARBONATES
NATIVE GRAPHITES
CALCIUM
'alum IN 0
SILICATES
CARBONO
SILICATES
CARBONATES
CO2
CARBIDES
QO^-METALLIC CARBONATES
DIAMONDS^
Fig. 12. The circulation of carbon (after Vernadskii).
Sources of energy.
Nevertheless these investigations are of great interest to
us in spite of the false assumptions on which they were based
because they revealed the sources of energy which could be
used on the primitive Earth, if not for the reduction of
carbon dioxide, then for the oxidation and transformation of
the primaeval hydrocarbons.
Solar radiation would seem to have been the greatest source
of energy on the surface of the Earth. The over-all amount
of energy of the solar radiation reaching the outer limits of
the atmosphere is 1-2 x 10'' kcal/year-^*' About 55 per cent
of this energy is absorbed by the atmosphere and giound
and, after a number of transformations, it leaves the Earth
11
l62 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
in the form of infra-red radiations. The rest is reflected
unchanged into space. ^^
According to A. E. H. Meyer and F. O. Seitz,^^ 6-3 per
cent of all the solar radiation reaching the outermost layers
of the atmosphere is in the form of ultraviolet radiation
having a wavelength between 4,000 and 3,150 A, while that
having a wavelength of less than 3,150 A amounts to only
about 0-6 per cent. On the basis of direct measurements
obtained by sending rockets to great heights, however, J. A.
Sanderson and E. O. Hulbert^* give the intensity of the ultra-
violet radiation (from 4,000 A downwards) as five times
greater, namely 4-8 x 10-° kcal/year.
As early as 1913 B. Moore,^^ proceeding from A. Baeyer's
theory of photosynthesis, put forward the idea that the pre-
requisite for the development of the organic substances neces-
sary to life was the formation of formaldehyde from the
primaeval carbon dioxide as the result of the action of solar
ultraviolet radiations. We find this same idea later in the
writings of P. Becquerel,^*^ J. B. S. Haldane," and, especially,
in a number of works by A. Dauvillier^* in which he elabor-
ates his photochemical theory of the origin of life. It was
shown, long ago, that carbon dioxide gives a series of absorp-
tion bands in the ultraviolet region of the spectrum from
1,710 A downwards. In absorbing these radiations it splits
to form CO and o (some of which finally appears as ozone). ^^
In the presence of water which is undergoing ultraviolet
photolysis we may suppose that CO2 could be reduced by the
hydrogen according to the equations :
2H20->2H2-l-02
2H2 -I- C02-^CH20 + H2O
H,0 -I- COo-^CHoO + O2
H. Thiele,*" however, did not find formaldehyde when he
submitted mixtures of hydrogen and carbon dioxide to ultra-
violet irradiation ; on the other hand, D. Berthelot and H.
Gaudechon," and later A. Coehn and G. Sieper,^^ established
that a small amount of formaldehyde is formed under these
circumstances. C. Zenghelis*^ also described experiments in
which carbon dioxide gas was reduced by hydrogen under
SOURCES OF ENERGY 163
ultraviolet irradiation to give formaldehyde which then
underwent polymerisation.
E. Rabinowitch has reviewed the extensive, though highly
contradictory, literature on the subject of the formation of
formaldehyde from aqueous solutions of carbon dioxide
during ultraviolet irradiation. From this literature it appears
that such formation, if it occurs at all, does so only to a very
limited and sometimes scarcely perceptible extent.
Under natural conditions this reaction could not give rise
to large amounts of organic substances, as the oxygen formed
in it would very soon set up an ozone screen, preventing the
access of short-wave ultraviolet radiations to the louver lavers
of the atmosphere. This is also the usual explanation for the
absence of reactions by which co, is reduced under the in-
fluence of ultraviolet radiation on the Earth at present.
N. R. Dhar and A. Ram,''* however, claim to have found
some thousandths of i per cent of formaldehyde in rainwater.
They suggest that this formaldehyde was formed photochemi-
cally in that part of the atmosphere which lies oiUside the
ozone screen. It would, however, be hard to prove that these
infinitesimal amounts of formaldehyde were formed in this,
rather than in some other way.
The second source of energy in the atmosphere of the
Earth is electrical discharges, either silent or in thunder.
It is very hard to calculate the amount of this energy. If, as
is usually done, we assume that under contemporary condi-
tions one flash of lightning strikes the ground for every square
kilometre of the surface of the Earth each year,^^ and that
the mean energy of a flash is lo^'' ergs,"**^ then the ^vhole
surface of the Earth receives 5-1 x 10* x 10^^ = 5-1 x 10"
ergs/year or 1-2 x 10^^ kcal/year. It follows that the energy
of electrical discharges is several orders lower than that of
ultraviolet light. This calculation, however, only takes into
account the noisy discharges of thimderstorms and it may be
that the energy of silent discharges in the atmosphere is also
quite considerable. There is also reason to suppose that
thunderstorms were more frequent in primaeval times.
As early as 1899 F. Allen''^ suggested the possibility that
the energy of electrical discharges in the atmosphere might
have been used in carrying out many organic syntheses on
164 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
the primaeval Earth. In particular, he disregarded con-
temporary conditions and considered that lightning was
continually striking through the primaeval atmosphere and
converting the molecular nitrogen in it into ammonia and
oxides which reacted with carbon dioxide and thus produced
what Allen regarded as the original carbon compounds on
the Earth.
C. B. Lipman** also assumed greater electrical activity in
the primaeval atmosphere when he tried to explain the
formation there of organic compounds from carbon dioxide,
water and nitrates. In his book R. Beutner'^^ also assumes
that in the primaeval atmosphere, consisting of carbon di-
oxide, water vapour and ammonia, complicated organic com-
pounds were formed as the result of powerful electrical dis-
charges.
It is true that these conclusions were arrived at in an
a priori way without any profound physico-chemical analysis
of the phenomena under discussion. It was, however, already
known in M. Berthelot's^" time that under the influence of
flashing, and in particular, of silent discharges of electricity,
carbon dioxide could be reduced by hydrogen to carbon mon-
oxide with the formation of small amounts of organic sub-
stances having the general formulae (ch2o)„ or (cH402)n. Later
W. Lob,^^ S. M. Losanitsch," and others" showed experi-
mentally that in silent electrical discharges a mixture of
water and carbon dioxide can form formic acid and formalde-
hyde, which are further transformed into glycolic aldehyde
which then polymerises to form carbohydrates.
On the basis of such observations one may presume that
in the atmosphere of the Earth at the present time minimal
quantities of organic substances are formed from water and
carbon dioxide as the result of flash or silent discharges. This,
of course, could also have taken place in the primaeval atmo-
sphere, though it is doubtful whether the reduction of carbon
dioxide played any substantial part in view of the very small
concentration of carbon dioxide then present.
A far more important effect of electrical discharges was
the transformation of the hydrocarbons of the primaeval
atmosphere, to which we shall return later.
As the third source of energy on the surface of the Earth
SOURCES OF ENERGY 165
we must mention the energy of the disintegration of the
atoms of the naturally radioactive substances, which were,
for the most part, concentrated in the granitic envelope of
the lithosphere. The heat passing from the centre of the
Earth to its surface amounts to lo^^ ergs /year or 2-5 x 10^'
kcal/year/** This is some thousands of times less than the
amount of energy received by the surface of the Earth from
the Sun.
G. Boitkevich'^ estimates the total amount of radiogenic
heat of the crust of the Earth at 4-7 x 10'^ kcal/hour or
4-1 X 10^* kcal/year. Even if we assume that the radioactivity
of the Earth was several times greater in the remote past
than it is now (on account of the breakdown of *°k and -^^u),
amounting to 2 x 10" kcal/year, the radioactivity of the
crust of the Earth must have played a considerably smaller
part in the chemical transformation of carbon compounds
than the energy of light, the more so as the greater part
of the radioactive energy was dissipated as heat. Neverthe-
less, we certainly cannot discount it/®
As early as 1913 J. Stoklasa and colleagues" drew attention
to the possibility that the primary synthesis of sugars from
cOo could occur under the influence of radium emanation.
We meet with the same idea in the works of many later
authors such as Becquerel, who invoked the radioactivity of
primaeval rocks (purely speculatively, it is true) as well as
ultraviolet radiations as the source of energy for the reduc-
tion of carbon dioxide. The possibility that a reduction of
this sort might have occurred is, to some extent, confirmed
by laboratory investigations. For example, S. C. Lind and
D. C. BardwelP^ obtained resinous organic substances by
allowing a-particles to act on mixtures of carbon dioxide or
carbon monoxide with hydrogen or methane. V. Sokolov^^
communicated some very interesting facts to the seventeenth
session of the International Geological Congress in Mosco^v
in 1937. On the basis of his own experiments he showed
that the water contained in sedimentary formations could
be decomposed to hydrogen and oxygen under the influence
of the a-rays of radioactive elements. If the oxygen is removed
in oxidising incompletely oxidised substances, in particular
metals and organic compounds, then the hydrogen can reduce
l66 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
carbon dioxide to methane, whicli later polymerises to form
ethane and other compounds of higher molecular weight.
W. M. Garrison, D. C. Morrison, J. G. Hamilton, A. A.
Benson and M. Calvin'' ° have recently published their studies
on the reduction of carbon dioxide in aqueous solutions
under the influence of ionising radiations. In their experi-
ments these authors proceeded from the assumption that the
formation of organic substances on the primaeval Earth was
achieved by the reduction of carbon dioxide under the in-
fluence of ionising radiations. To test this assumption they
submitted aqueous solutions of carbon dioxide to the action
of a stream of helium particles in a cyclotron and were able
to show definitely that formic acid and formaldehyde were
present among the products of the reaction.
Phenomena of this kind may, of course, occur in the crust
of the Earth at present to a very limited extent, but under
the reduced conditions of the primaeval Earth they could
hardly have been of decisive significance owing to the small
amounts of carbon dioxide present there.
All the sources of energy which we have enumerated (ultra-
violet and cosmic radiation, electric discharges and radio-
active breakdown) must have played important parts in the
early history of our planet, not only by bringing about reduc-
tion of carbon dioxide (which was scarcely present in large
amounts) but by transforming hydrocarbons which were, at
that time, the most abundant carbon compounds. The chemi-
cal evolution of the hydrocarbons could have been accom-
plished simply on the basis of their own energy potentials,
but the practical realisation of these potentialities was greatly
facilitated by the presence of supplementary sources of
energy. Short-wave ultraviolet radiation, silent electric dis-
charges and a-particles brought about specific transforma-
tions of organic molecules by stages, with the formation of a
series of intermediate compounds. We must bear in mind
that the hydrocarbons and their derivatives which were
originally formed in the lithosphere, where the temperature
and pressure may have been comparatively high, afterwards
migrated, for the most part, into a moist atmosphere, the
various layers of which were subjected to cold and the action
of light and electric discharges, and that the products which
SOURCES OF ENERGY 167
made their appearance there could accumulate and be
further transformed in the waters of the hydrosphere. Under
these circumstances we must expect a considerable variety
of organic substances on the surface of the Earth. There
might, indeed, have arisen representatives of all such com-
pounds known to us. The difficulty which faces us when we
try to give a concrete account of the course of organic evolu-
tion on the Earth lies not so much in the absence or insuffici-
ency of chemical possibilities, as in the number of alternative
intersecting routes along which any particular organic mole-
cule could have been transformed.
As was shown in Chapter IV, the main source from which
the abiogenic hydrocarbons of the surface of the Earth were
derived was the lithosphere.
As early as 1889 V. Sokolov^^ put forward the hypothesis
that the primary hydrocarbons of the Earth ^vere taken up
by molten magmata and that when these cooled and solidified
the hydrocarbons could once more separate out and that
they are still separating out in fissures in the lithosphere.
Such a hypothesis, however, seems extremely improbable in
the light of present-day astronomical and geological evidence.
The main forms in which carbon was retained on the Earth
during its formation were, as we have already seen, native
carbon and carbides. During the development of the litho-
sphere they interacted with geological formations incorporat-
ing hydrates or other forms of constitutional water. Accord-
ing to R. Goranson" molten magma contains 5 per cent or
more of water. The geological formations of the primaeval
Earth must have been e\en richer in water, for the hydro-
sphere contained only one-tenth as much water then as it
does now and the rest of the water was still bound in the
lithosphere.
It is well known that, on reaction with water, carbides of
calcium, barium, strontium and lithium give rise to acety-
lene, those of aluminium and beryllium to methane, that
of manganese to mixtures of methane and hydrogen, those of
the rare metals to mixtures of acetylene and methane, while
carbides of uranium give rise to mixtures of methane, hydro-
gen, ethylene, and liquid and solid hydrocarbons, etc.®^
Many carbides are not decomposed by water at ordinary
l68 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
low temperatures, but yield hydrocarbons when heated to
temperatures such as might easily be reached in the litho-
sphere. Under these conditions the formation of hydro-
carbons could also take place by the direct reduction of
carbides by hydrogen.
Even now hydrogen is given off by the lithosphere in
considerable amounts ; it is an important constituent of
inflammable volcanic gases. ^^^ Of course, the hydrogen given
off now may be partly of secondary origin, arising as the result
of the breakdown of biogenic substances. Its formation by
inorganic means is, however, by no means excluded. G.
Stadnikov,®* for example, put forward the possibility that
hydrogen might be formed thermally in the interior of the
Earth by the action of water vapour on red-hot solutions of
carbides in ferromanganese. A. Gaedicke®^ invoked the action
of the a-particles of the radioactive elements on the water of
the deep geological formations
(n + i)h20 — >2(n + i)h + (n+i)o
The hydrogen arising from this reaction might escape
directly into the atmosphere or might form hydrocarbons
by reacting with carbon (e.g. with graphite) according to
the equation:
nc + 2{n+ i)h >c„H(2„^,)
Under the strongly reducing conditions which were present
on the primaeval Earth the opportunities for the formation
of free hydrogen must have been far greater than they are
now.
S. C. Schuman®® has calculated the equilibrium constants
for the reactions :
FeoC + (2/2 - i)H2 + {n - l)cO >C„H2„ -f 2Fe + {u - i)H20
Fe2C + 2«H2 + {n - l)C0 ^C„H(2„+2) + 2Fe + {u - i)H20
The results of these calculations showed that the forma-
tion of hydrocarbons from iron carbide by direct reduction
is perfectly possible thermodynamically, at temperatures of
250° - 350° C, that is to say, under conditions which may
easily obtain in the lithosphere.
The hydrocarbons which appeared during the formation
SOURCES OF ENERGY 169
of the crust of the Earth (mainly methane, ethane, acetylene,
etc.) were, in part, given off directly into the atmosphere
while, in part, they under^vent various chemical changes
Avithin the lithosphere itself. We will only discuss a few of
the many reactions which may have taken place there.
The simple thermal polymerisation of methane to ethane,
propane and other higher hydrocarbons would seem to be
out of the question, since ethane cannot be formed at tem-
peratures above 227° C or propane above 180° C and, within
the limits of these temperatures, methane is quite stable and
has no tendency to dehydrogenation or polymerisation. It
has, however, been shown by V. Sokolov that, under the
action of a-radiation from the radioactive elements of the
crust of the Earth, the molecules of methane may become
more complicated with the evolution of hydrogen and the
formation of ethane and also of the simplest olefines. Further
polymerisation takes place, with the formation of gaseous
and liquid hydrocarbons of high molecular weight.
Without receiving energy from external sources molecules
of methane can undergo conversion according to the equa-
tion":
CH4 -t- H20->C0 -f 3H2
The change in free energy, Az cal/mole, in this equation
has been calculated by A. Pasynskii from the table of V.
Korobov and A. Frost : ®*
Az= - 49270 + 5i-3T-f ii-i/ (t/ 298- 16)*
It only enters a region of positive values (w^hen the process
comes to a standstill spontaneously for thermodynamic
reasons) above 650° C.
At far lower temperatures (of the order of 100-200° C),
though under increased pressure, methanol is formed from
carbon monoxide and hydrogen according to the equation:
CO -t- 2Ho->CH30H
* In this calculation, as in those which follow, values for AZ have been
calculated for standard conditions and for the ,a;aseous state. T is tempera-
ture in degrees Absolute. The function / (T/298-i6) = Ln (T/298-i6)-f
(298-16/T) — 1. All have been made by A. Pasynskii from the table of
Korobov and Frost. — Author.
170 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
For this reaction Az= — 21680 + 52-7T, which means that
it is thermodynamically possible up to 200° C.
The next important reaction whicli methane can undergo
is that with ammonia and ammonium salts as follows:
CH4 + NHg-^CHaNH, + 2H
According to V. Dolgov^^ it is thermodynamically possible
for this reaction to take place at temperatures of 500° C and
higher, with the formation of methylamine.
The chemical potentialities of ethylene and acetylene are
far wider. We must first discuss the various reactions in
which these compounds are hydrogenated and polymerised,
leading to the formation of saturated hydrocarbons, of higher
members of the olefine series, to ring formation into poly-
methylenes, and so forth.
All these reactions are possible from a thermodynamic
point of view at temperatures below 500° C.
The polymerisation of the gaseous olefines of low mole-
cular Aveight is accompanied by a decrease in volume. The
increased pressure in the lithosphere would, therefore, favour
its occurrence.''"
The hydration of ethylene and acetylene is easily brought
about by their reaction with water. In the presence of specific
catalysts such as AI2O3, W2O5 etc., the reaction C2H4-fH20 ^
C2H5OH can occur at temperatures of about 100° C if the
pressure is high.^^
Acetylene is hydrated by Kucherov's reaction to gi\e
acetaldehyde, C2H2 -1- H20->ch3CH0. This reaction occurs in
the presence of a number of catalysts ; even iron ore will
bring it about. The equation for its free energy is as follows:
Az =- 35890 -H 29-5T -f 3-5/ (t/ 298- 16)
and shows that it is thermodynamically possible for the
reaction to occur at temperatures of 900° C and below.
Acetylene can also be hydrated to form acetone :
2C2H2 + 3H0O >CH3.CO.CH3 + COn + 2H2
This reaction is usually carried out technically at tempera-
tures of 450- 470° C with the help of catalysts — oxides of
SOURCES OF ENERGY 171
iron, manganese, zinc, vanadium, etc. Thermodynamic cal-
culations give the equation
Az= -80822 + 47- IT + 4/ (t/ 298- 16)
which means that the reaction could occur at the tempera-
ture of the lithosphere.
We may also mention some reactions between acetylene
and formaldehyde. One of these in particular gives rise to
propargyl alcohol:
C2H. + CH20^HC=C.CH20H
and a large number of more complicated products — glycerol,
erythritol, hexamethylolbenzene, etc. Tens of different spon-
taneously occurring reactions have also been described in
which acetylene is condensed with alcohols, ethers, acids,
aromatic compounds, etc.^^
Acetylene can also react ^vith water or hydrogen sulphide
to give heterocyclic compounds. For example, A. Chichi-
babin''^ obtained a condensate containing furan by passing
steam and acetylene over ai._03 at 400-425° C:
2C2H0 + H20^C4H40 + Ho
For this process Az= -56680 + 51T from which it is clear
that, from a thermodynamic point of view, it can occur right
up to 800° C.
The corresponding calculation for the reaction by which
thiophene is formed (2C2H2 + H2S->C4H4S + Ho) gives Az =
- 22760 + 43-3T which suggests that the temperature at which
this reaction is thermodynamically possible may be as high
as 250° C.
An interesting possibility for the transformation of the
primary hydrocarbons of the lithosphere is provided by the
reaction known as the 0x0 synthesis.^* This consists in the
simultaneous condensation of olefines ^vith hydrogen and
carbon monoxide (which can here be formed by the con-
version of methane), e.g. :
CO + C2H4 -f Ho-^CHg.CHi-CHO
Many different aldehydes may arise in this way and then
give rise to the corresponding alcohols and acids. Acrylic
172 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
acid formed from acetylene and carbon monoxide at 115° C
and 100 atmospheres goes on to form succinic acid according
to the equation
CO
CH2 = CH.COOH >HOOC.CH2.CH2.COOH
HoO
Oxo syntheses can occur with any unsaturated compounds,
including aromatic ones.
Under the conditions prevailing in the primaeval litho-
sphere many reactions leading to the formation of nitrogen-
ous substances could also occur. In addition to the formation
of methylamine as described above, we must now mention
the formation of ethylamine and acetonitrile by the catalytic
condensation of acetylene and ammonia when they pass over
bauxite, permutite or other catalysts at 400° C.
Long ago Berthelot described the synthesis of pyrrole and
other nitrogenous heterocyclic compounds as the result of
the action of acetylene on ammonia, diazomethane and
hydrocyanic acid. A. Chichibabin''^ has shown that pyrrole
and some pyridine bases are formed from acetylene and
ammonia in the presence of AioOg, FeaOs, or CroOg at 300° C.
CH - CH
,f;H II II
2 III +NH3 > CH CH -fHo
CH \ /
NH
Similar syntheses have been described in detail by A. P.
Terent'ev and L. A. Yanovskaya.^^ T. Ishiguro, S. Kubota,
O. Kimura and S. Shimomura^^ have recently described
experiments in which they obtained pyridine (C5H5N) and
its homologues by condensing acetylene and ammonia in
the presence of various catalysts at temperatures of about
300 - 400° C.
Most of the reactions which have just been mentioned
can easily be carried out in the laboratory or on an industrial
scale for the manufacture of one or other of the products.
Their occurrence, however, cannot by any means always be
observed in nature, as it is now complicated and obscured
by the changes taking place in carbon compounds which have
SOURCES OF ENERGY l73
arisen secondarily and have been laid down in the crust of
the Earth as a result of the activities of living organisms.
At present ^\e can see in many places the transformation of
secondary organic compounds in the lithosphere. A particu-
lar example of this is the formation of petroleum. In this,
the organic remains of animals and plants which have been
heated in the depths of the crust of the Earth undergo re-
actions involving the breakdown of those large, complicated
molecules, rich in oxygen and nitrogen, which have previ-
ously been synthesised by living things. On the whole these
phenomena are proceeding in the opposite direction from
the reactions which have been described above. Compounds
of high molecular weight are broken down and new ones
are formed in place of them. Compounds containing oxygen,
nitrogen, phosphorus and sulphur are almost completely
decomposed, their hydrogen content is inCTeased and new
cyclic and polycyclic hydrocarbons, etc., emerge.^* It is only
on rare and isolated occasions that these phenomena of the
degradation of pre-formed organic substances can be used
directly to form an estimate of the primitive synthetic pro-
cesses which occurred on the Earth before the appearance
of life.
A study of the formation of petroleum and, in particular,
of that of natural gas can, however, make a great contribution
towards the solution of the problem before us. It shows that
the results which are obtained under artificial conditions
in the laboratory are completely confirmed in nature. This
applies both to the influence of temperature and pressure on
the complicated processes of transformation of organic sub-
stances in the crust of the Earth, and also to the effects of
various artificial and natural catalysts on these processes.
The remarkable geochemical ideas on this subject put
forward by N. Zelinskii"' on the basis of his laboratory
experiments have been completely confirmed by the investi-
gations of the formation of petroleum by many scientists in
Russia and other countries.^" According to S. N. Obryad-
chikov" and A. V. Frost, *^ petroleum is formed at compara-
tively low temperatures, about ioo-300°C. V. Porfir'ev,*^
on the other hand, suggests the figure of 500° C. Even higher
temperatures may certainly be encountered in different zones
174 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
of the crust of the Earth but it would seem not to be these
which play the decisive part in the formation of petroleum,
but rather the catalytic activity of the mineral formations.
In particular, A. V. Frost*^ has shown that those reactions
which, in the laboratory, are catalysed by anhydrous alu-
minium chloride can also take place in the presence of various
natural clays (kaolins, bauxites and other aluminosilicates)
without any preliminary treatment or activation/^
Similarly, the transformations of the primary hydrocarbons
which have already been described may take place in the
crust of the Earth, being catalysed by oxides of aluminium,
iron, chromium and manganese and by other substances
which are widely distributed in the lithosphere.
The multiplicity of possible chemical transformations is
further considerably increased in the crust of the Earth
by the influence of the decay of the radioactive elements
which are present there. Under these conditions reactions
can occur which would be prohibited by thermodynamic
considerations from occurring on their own. Among these
we may mention the formation of acetaldehyde by the
reaction between methane and carbon monoxide and the
dehydrogenation of methane and its polymerisation, which
have already been discussed in relation to the work of V.
Sokolov, as well as other reactions.
One of the first to point out the possible significance of
radioactive substances in the formation of petroleum was
N. Zelinskii.'' As early as 1925 V. Sokolov*' produced evi-
dence for the occurrence of natural radioactivity in clays and
other geological formations. I. A. Breger and W. L. White-
head,** A. Kozlov,** M. Karasev,*^ and many other workers
have also studied the significance of radioactivity in the
formation of petroleum.
One can, however, hardly regard (as some authors do) the
radioactivity of geological formations as being solely respons-
ible for the origin of the hydrocarbons which were first
formed in the crust of the Earth. Direct catalytic transforma-
tions must certainly have been more important quantita-
tively. Radioactive radiations may, however, have been
responsible for the occurrence of reactions which would
otherwise have been impossible on thermodynamic grounds.
SOURCES OF ENERGY l75
One must, therefore, take these radiations into consideration
if one wislies to picture to oneself the course of the chemical
transformation which took place in the primaeval lithosphere.
Only a small proportion of the primary hydrocarbons and
their derivatives (mainly compounds of high molecular
^veight) were retained in the lithosphere and later extracted
from it by the waters of the hydrosphere. All the volatile
carbon compounds were gradually given off from the crust
of the Earth into the atmosphere, just as we may now observe
the giving off of natural gases. The most important and most
frequently encountered of these gaseous hydrocarbons is meth-
ane.'^" At present, of course, it is partly formed secondarily, by
the breakdown of biogenic organic substances or by the reduc-
tion of carbon dioxide. According to V. Vernadskii, however,
methane occupies an important place among the carbon
compounds originating in the depths of the Earth. Hardly
anyone will deny the possibility that even now it is formed,
at least in part, as the result of inorganic processes, in volcanic
gases and emanations.
As well as methane, the primitive atmosphere of the Earth
must have contained carbon monoxide which was formed
from methane. Ethylene and acetylene were more likely to
have undergone reactions of some kind while still in the
lithosphere on account of their chemical reactivity, which is
far gi'eater than that of methane. The average specific gravity
of the gases composing the primitive atmosphere must, there-
fore, have been relatively lo^v, which is what we now obser\ e
in natural gases.
In the atmosphere the primary hydrocarbons and their
derivatives encountered new sources of energy which were
not present in the lithosphere. Electrical discharges" and
ultraviolet radiation®- enabled them readily to surmount the
barrier of the energy of activation and even to enter into
reactions which would be thermodynamically impossible in
the absence of external supplies of energy. For this reason
new reactions occurred in the atmosphere in addition to those
taking place in the absence of the factors just mentioned
(electrical discharges and ultraviolet radiations) and the
transformation of hydrocarbons was much wider in its scope.
In the atmosphere even such a chemically inert gas as
176 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
methane could serve as the basis for the formation of the
most varied organic substances. As we have already seen,
the direct thermal dehydrogenation of methane requires very
high temperatures, at which it cannot polymerise. Under
the influence of electrical discharges, on the other hand,
methane polymerises easily with the formation of various
gaseous, liquid and solid products, as had already been
demonstrated by the end of the nineteenth century.^'
Acetylene, ethylene, diacetylene, benzene, naphthalene,
acetonaphthene, dipropargyl and many other hydrocarbons,
some of very high molecular weights, have been identified
during the study of the composition of these products. Most
of the substances listed arise as the result of the secondary
transformation of acetylene, which is to be regarded as one
of the fundamental products of the dehydrogenation and
polymerisation of methane under the influence of electric
discharges.'*
R. V. de St.-Aunay®^ submitted methane to the action of
silent discharges in a circulating system and this allowed him
to form an opinion as to the earliest stages of the process. On
the basis of this work he wrote as follows :
At the very beginning of the activity of the discharge the
methane was split to hydrogen and a free radical which led to
a slight decrease in the volume of the gas on condensing. Ethane
was formed from methane without any change in volume,
and as it accumulated it was dehydrogenated, which gave an
increase in the volume, CaHg-^CaH^ +H2. The ethylene thus
formed was dehydrogenated in its turn. When enough ethylene
and acetylene had accumulated a further decrease in volume
took place, due to their polymerisation.
The polymerisation in the electric discharge of ethane, '*®
ethylene^'^ and, especially, of acetylene,'^ leads to the forma-
tion of a countless variety of compounds both aliphatic and
cyclic. This variety of products is greatly increased ^vhen the
electric discharges act on mixtures of hydrocarbons, e.g.
CoHo-fCH^; CoH^ + CH^;^^ C2H2-fC2H4 ;^'"' C6H6 + CH4/" etc.
Unfortunately these reactions have not yet been studied in
anything like full detail.
SOURCES OF ENERGY 177
A large number of oxygen-containing derivatives ot hydro-
carbons are also easily formed under the influence of electric
discharges. The conversion of methane, CH4 + HoO^co + 3H2,
which could only take place in the lithosphere at compara-
tively high temperatures, occurred in the cold in the primi-
tive atmosphere by making use of the energy of electric
discharges. The carbon monoxide thus formed reacted, in its
turn, with methane, according to the equation:
CH4 -f CO-^CH3.CHO
Calculations for this reaction give Az = 4,800 -f 28-2T. This
means that, for thermodynamic reasons, the reaction by
which acetaldehyde is formed from methane and carbon
monoxide cannot occur spontaneously at any" temperature.
Nevertheless S. M. Losanitsch and M. Z. Jowitschitsch^"^
submitted a mixture of carbon monoxide and methane to the
action of silent discharges and obtained an oily condensation
product containing acetaldehyde. On continued action of
the discharge this polymerised to aldol and more complicated
condensation products.
QCHa.CHO-^CHj.CHOH.CHo.CHO^ (CHa.CHOH.CHo.CHO)^
The acetaldehyde itself forms a number of gaseous and
liquid products when its vapour is mixed with hydrogen and
submitted to the action of a silent discharge. The following
equations express some of the individual reactions"^:
2CH3.CHo->H2 + CO + CH3.co.CH3 (acetone)
3CH3.CH0^2H2 + 2CO + C2H5.CO.CH3 (methyl ethyl ketone)
2CH3.CHO-^H2 + CH3.CO.CO.CH3 (diacetyl)
2CH3.CHO^C2H4 + CH3.C00H (acetic acid)
4CH3.CHO->C2H4 + 2C2H5.COOH (propionic acid)
Reactions by which aldehydes are formed directly from
hydrocarbons and carbon monoxide appear to be very
general. For example, under action of electric discharges
a mixture of ethylene and carbon monoxide gives rise to
acrolein,"'^
CH2:CH2 + CO-^CHolCH.CHO
12
178 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
a mixture of benzene and carbon monoxide to benzaldehyde
and so forth.
Acetaldehyde and its condensation products are formed
from mixtures of acetylene and water under such conditions.
If a mixture of benzene and water is submitted to an electric
discharge phenol will be formed.
Carbon monoxide can also react directly with hydrogen
to give formaldehyde. This reaction is brought about by
electric discharges, though only to a very small extent."^
Reactions between hydrocarbons and their derivatives and
ammonia must also have occurred extensively in the primi-
tive atmosphere. In this connection we must first discuss the
reactions by which hydrocyanic acid is formed:
CH4 + NH3->HCN + 3H2 — 60 kcal
C2H4 + 2NH3->2HCN + 4H2 63 kcal
C2H2 + 2NH3->2HCN + 3H2— 28 kcal
CO + NHj-^HCN -f HoO — 1 o kcal
These reactions are all endothermic but they proceed
satisfactorily when an electric discharge passes through a
mixture of the gases. ^°^ Hydrocyanic acid is also formed in
this way in mixtures of hydrocarbons and molecular nitro-
gen. This latter could have arisen in the primitive atmo-
sphere by the oxidation of ammonia by the free oxygen
derived from the photolysis of water. Long ago, Berthelot
showed that hydrocyanic acid was synthesised at the expense
of molecular nitrogen when this was mixed with acetylene
and submitted to arc"^ or flash^"* discharges. H. Becker
showed later that a similar process may take place with silent
discharges. ^°^
One of the many products of such discharges in a mixture
of nitrogen, carbon monoxide and hydrogen is urea.^" This
is probably formed by a reaction between carbon monoxide
and ammonia, the ammonia having previously been formed
from hydrogen and nitrogen.
No + SHo-^QNHg
2NH3 + CO->NH2.CO.NH2 -f H2
Reactions between hydrocarbons and hydrocyanic acid or
SOURCES OF ENERGY 1 79
ammonia give rise to a whole series of different, and some-
times very complicated, products including nitriles, amines,
amides, etc. For example, the action of a silent discharge on
a mixture of ethylene and hydrocyanic acid gives propio-
nitrile^^^
C2H4 + HCN->C2H5CN
If acetylene is substituted for ethylene the isonitrile and
succinodinitrile are formed" -
2HCN + CoHo-^NC.CHa.CHs.CN
When mixed with ammonia in silent discharges ethylene
gives ethylamine
C2H4 + NHs-^CaH^NH,
According to the evidence of S. M. Losanitsch,"^ when
ammonia reacts with ethylene, acetylene, benzene and other
hydrocarbons one obtains a large amount of various compli-
cated nitrogen-containing compounds of very high molecular
weight.
From our point of view the formation of amino acids
under these conditions is of special interest, as they are the
fundamental components in the structure of protein-like
substances.
Recently the follo^ving experiment, based on the evidence
now available as to the composition of the atmosphere of
the primaeval Earth, was carried out by S. L. Miller."^ He
used apparatus specially constructed for the purpose and
passed silent electric discharges through a mixture of
methane, ammonia, hydrogen and water vapour and ob-
tained a number of amino acids — glycine, dl -alanine, /3-
alanine, sarcosine, DL-a-aminobutyric and a-aminowobutyric
acids. A considerable amount of other amino acids which
have not yet been identified was also shown to be present.
As well as these, glycolic, lactic, formic, acetic and propionic
acids were found. A considerable amount of hydrocyanic
acid and aldehydes was also present and these seem to have
been produced directly by the action of the discharges.
According to Miller there are two possible explanations
l8o ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
for the way in which these higher products of the reaction
were formed:
(i) Hydrocyanic acid, amines, aldehydes, alcohols, most of
the volatile acids and acrylonitrile were formed in the elec-
tric discharge. The amino acids, hydroxy acids, some of the
fatty acids and the polymers only arose in solution.
(2) All the substances which were found arose in the silent
discharges in the gaseous phase as the result of reactions
between free radicals and ions.
Assuming the former hypothesis to be correct, Miller has
drawn up the following set of equations for the formation
of amino acids:
R.CHO + NH3 + HCN^R.CHNHa.CN -|- H2O
R.CHNH2.CN -I- 2H20->R.CHNH2.COOH -1- NH3
and hydroxy acids :
R.CHO -1- HCN->R.CHOH.CN
R.CHOH.CN + 2H20^R.CHOH.COOH + NH3
S. L. Miller's experiments were repeated and completely
confirmed by A. Pasynskii and T. Pavlovskaya."'^ According
to Pasynskii's calculations the value of Az for the formation
of alanine from methane, water and ammonia was 461004-
50-8t from which it may be seen that Az>o at all tempera-
tures. It follows that the reaction cannot occur spontaneously
but requires the extra energy of the electrical discharge. If,
however, the mixture of gases includes carbon monoxide,
Az for the reaction becomes — 52939 -f 153-4T and the re-
action is thermodynamically possible at ordinary tempera-
tures. This variant of Miller's reaction was reproduced
experimentally by Pasynskii and Pavlovskaya in an electric
field but the reaction has, so far, not been accomplished in
any other way.
We have already shown that a far more potent source of
energy for the synthesis of organic substances on the primae-
val Earth than that of electric discharges was provided by
solar radiation, in particular by ultraviolet radiation. At
present the only chemical processes which are observed to
occur under natural conditions on the surface of the
SOURCES OF ENERGY l8l
Earth under the influence of ukraviolet light are on a very
limited scale. This is because the short-wave radiations,
Avhich are by far the most active, are almost entirely absorbed
by the ozone screen. It is, however, appropriate to refer, at
this point, to the recently published work of K. Bahadur.^ ^^
This author claims to have succeeded in synthesising various
amino acids from paraformaldehyde and potassium nitrate
in the presence of iron chloride by allowing these substances
to stand in aqueous solution in direct sunlight for 80 hours.
The formation of amino acids did not take place in the
dark or in the absence of iron chloride. Bahadur claims
that in his experiments he observed the synthesis of the
following amino acids: arginine, valine, histidine, proline,
lysine, serine, aspartic acid, glycine, ornithine and asparagine.
According to K. Bahadur and S. Ranganayaki"^ the pro-
cess proceeds through the following intermediate reactions :
2CH2O -I- HaO-^CHgOH + H.COOH
CH2O + H.COOH^HOCHo.COOH
HOCHa.COOH-^CHO.COOH + 2H
The nitrate is reduced to ammonia at the expense of the
formaldehyde
CHO.COOH + 2NH3->NH2CHOH.COONH4
NH2CHOH.COONH4 -f H.O^NH^CHOH.COOH -f NH^OH
NH2CHOH.COOH-^NH : CH.COOH + HoO
NH : CH.COOH + QH^NHoCH^-COOH (glycine)
NH : CH.COOH 4- CH20-^CHO.CHNH2.COOH
CH0.CHNH2.C00H + 2H->CH20H.CHNH2.cooH (serine)
CH2O -f CH20H.CHNH2.COOH->CHO.CH2.CHNH2.COOH + H2O
CHO.CH2.CHNH2.COOH -j- 2H^HOCH2.CH2.CHNH2.COOH
CH.O + HOCH2.CH2.CHNH2.COOH-^CHO.CH2.CH2.CHNH2.COOH -f H.O
CHO.CH2.CH2.CHNH2.COOH + 2H->HOCH2.CH2.CHo.CHNH2.COOH
CHo CH2 CH2 CH2
\ \
HC — COOH-> HC — COOK -f H2O
/ /
CH2OH H2N CH2 HN
(proline)
l82 ABIOGENIC O RG AN IC- C HE MI C AL EVOLUTION
It is, however, not dear from the paper to what extent the
authors were able to verify their sclieme by direct experi-
ment.
We sliall find a sounder experimental basis for our
opinions as to the changes which organic compounds must
have undergone in the primaeval atmosphere of the Earth
under the influence of ultraviolet radiations in the numerous
laboratory experiments using artificial sources of light. Like
water, ammonia and hydrocarbons are split when they absorb
radiations belonging to different parts of the ultraviolet spec-
trum. This leads to the formation of various radicals such as
— H, — OH, =NH, — NHa^ =CH, ^^CHa, — CH3, — CN, C2H, CgHo
and CgH^. When the gas is highly rarefied, as is the case in the
outer layers of the atmosphere, these radicals can exist as
such for a longer or shorter time. However, as the pressure
increases, their life span decreases quickly because they
combine with one another to form stable compounds. When
this happens, all possible combinations occur and thus there
arises a great diversity of substances.^^* Contemporary
scientific literature contains an immense amount of material
concerning the transformation of organic substances by ultra-
violet radiation. The saturated hydrocarbons only absorb
radiation of very short wavelength at the margin of the
ultraviolet spectrum but the olefines can also undergo chemi-
cal changes under the influence of radiations having a
wavelength greater than 2000 A. The action of ultraviolet
radiation brings about polymerisation and isomerisation of
these hydrocarbons. They are also oxidised, mainly at the
expense of the oxygen arising from the photolysis of water.
This oxidation leads to the formation of various alcohols,
aldehydes and ketones, which can be further oxidised or
broken down photochemically to give co, H2 and new
derivatives. Under the continued action of ultraviolet
radiation the monobasic acids thus formed give rise to co,,
hydrocarbons and small amounts of co and Ho. The dibasic
acids lose CO2 and are transformed into monobasic ones.
Various nitrogen-containing derivatives may also easily be
formed by reactions with ammonia, hydrazine and such sub-
stances. ^^^ In this way the great diversity of oxygen- and
nitrogen-containing derivatives of hydrocarbons which ap-
SOURCES OF ENERGY 183
peared in the primaeval atmosphere as a result of the action
of electric discharges was markedly augmented both in quan-
tity and quality by the action of ultraviolet radiation. Owing
to the selective activity of radiant energy on the surface of
the Earth new organic compounds appeared continually, and
the complication of their molecular structure was increasing
the whole time.
Methane absorbs ultraviolet radiation in the neighbour-
hood of 1,400 A, and especially strongly in the neighbourhood
of 1,295 ■^•^"" When this happens, it is split to methyl radicals
and atomic hydrogen. The final products of these trans-
formations of methane are hydrogen and acetylene as well as
ethylene, ethane and hydrocarbons with three, five and six
carbon atoms. ^^^
According to S. Tolloczko,^" when ethane is submitted
to ultraviolet irradiation it forms a light, colourless con-
densate made up of a mixture of hydrocarbons, chiefly hex-
ane, and a gas containing hydrogen and methane. When
ethylene is decomposed by ultraviolet radiation having a
wavelength shorter than 2,100 A, acetylene and hydrogen are
formed.^"
D. Berthelot and H. Gaudechon^^* observed a slow poly-
merisation of ethylene under ultraviolet irradiation. Accord-
ing to H. S. Taylor and D. G. HilP-' the polymerisation of
ethylene may lead to the formation of saturated hydro-
carbons, in particular to those of very high molecular weight
such as cuprene.
Acetylene also polymerises very easily and, under the
influence of idtraviolet irradiation, it gives rise to many
products, including benzene and naphthalene.^-^
Ethylene, acetylene and their derivatives may readily be
oxidised photochemically by oxygen to form aldehydes,
ketones and acids. For example, on irradiation in the
presence of oxygen ethylene gives rise to formic acid^^^ and
acetylene to oxalic acid and formaldehyde.^-* The oxidation
products can react with the hydrocarbons and their deriva-
tives to give more and more complicated organic substances
such as allyl alcohol, crotonic, maleic and tartaric acids, etc.
Ammonia absorbs ultraviolet light at wavelengths below
2,400 A. The maximum absorption is at 1,910- 1,935 ^-^^^
184 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
The primary photochemical reaction seems to be the
breakdown of ammonia according to the equation: nh3->
NHj + H.^'"' A number of derivatives can be formed from nHo,
especially hydrazine, NH2-NH2, which itself absorbs ultraviolet
radiation at 2,400 A and can then take part in chemical
reactions with other substances or be broken down according
to the equation 2 NoH4-^2 NH3 + N2 + H2.^^^ Molecular nitro-
gen could also have been formed in the primaeval atmo-
sphere by the direct oxidation of ammonia by the oxygen
liberated by the photolysis of water and the escape of
hydrogen. Reactions between nitrogen and hydrocarbons,
particularly methane, give rise to cyanogen derivatives.
When ammonia reacts photochemically with carbon mon-
oxide it gives formamide, with ethylene it gives vinylamine
and so forth. As a rule unsaturated hydrocarbons react
photochemically with ammonia to give cyclic compounds of
the nature of pyrrolidine or pyridine. ^^^
In the primaeval atmosphere of the Earth the hydro-
carbons could also react with hydrogen sulphide. This gas
was evolved during the formation of the lithosphere when
metallic sulphides were hydrolysed by the constitutional
water of the mineral formations. When it was given off into
the atmosphere it was enabled to react with the hydrocarbons
present there by the action of both electric discharges and
ultraviolet radiations. This must have led to the formation
of mercaptans and various products of their polymerisation, as
was observed by S. M. Losanitsch and M. Z. Jowitschitsch^^^
when they passed silent discharges through a mixture of HoS
and ethylene:
C2H4 -f H2S->CH3.CH2SH
6 CH3.CH2SH^(C2H4S)6 4- 6H2
In their book, to which reference has already been made,
C. Ellis and A. A. Wells^^ showed that on ultraviolet irradia-
tion from a quartz mercury lamp mercaptans (rsh) lose
their hydrogen and are converted into the corresponding
alkyl disulphides (r-s-s-r). Ultraviolet irradiation can also
bring about the formation and further alteration of thio-
glycolic acid, cysteine and other complicated organic com-
pounds of sulphur, particularly heterocyclic ones.
SOURCES OF ENERGY
i8r.
It is a peculiarity of ultraviolet radiation that its activity
is very selective. Sometimes it affects only a very limited
part of some particular molecule. Very delicate and specific
alterations may therefore be brought about by the action of
ultraviolet radiation on substances whose specific absorptive
capacity is strictly limited to a particular part of the ultra-
violet spectrum. An example of this, which is well known
to biologists, is the conversion of ergosterol to vitamin Do by
ultraviolet irradiation. ^^^
C9H17
In this reaction the complicated molecule remains unchanged
as a whole. It is only in the second ring of the phenanthrene
nucleus that one bond is broken, with the formation of a
double bond in the side chain. Other very diverse but always
highly specific stereoisomeric transformations of organic mole-
cules are well kno^vn to occur on irradiation with ultraviolet
light of strictly defined ^vavelength."^ In particular we must
note the cis-trans isomerisation of very many organic com-
pounds, both simple^^*^ and considerably more complicated
in structure."^ Finally, if ultraviolet light is circularly polar-
ised it can affect the optical isomerism of the compounds
formed, thus creating the conditions for direct asymmetric
synthesis. (We shall deal with this subject in more detail
somewhat later.)
Taking into account all that has been discussed, ^ve may
assume that in the atmosphere of the primaeval Earth many
diverse and complicated organic substances ^vere formed from
comparatively simple ones, mainly methane, ammonia, water
vapour and hydrogen sulphide, under the influence of elec-
tric discharges and ultraviolet radiation. With rain and other
precipitations these complicated substances fell into the
primitive hydrosphere. Having fallen into this new medium
they continued to change and become even more compli-
l86 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
cated, but in aqueous solution the process took on certain
new characteristics.
We must first say a few words as to the concentration of
organic substances which could have been attained in the
waters of the primaeval Earth. In this connection it is some-
times maintained that the quantity of hydrocarbons and their
derivatives formed on the surface of the Earth must have
been infinitesimal in comparison with the quantity of water
in the primitive ocean and that, consequently, their con-
centration was quite negligible. For this reason any further
transformation of the organic substances in the hydrosphere
was almost precluded because, on account of their great
dilution, the distances between the molecules were so great
that they could hardly come into contact with one another.
In this connection it may not be out of place to recall an
example once produced by Lord Kelvin^^
138
Suppose that you could mark the molecules in a glass of water ;
then pour the contents of the glass into the ocean and stir the
latter thoroughly so as to distribute the marked molecules uni-
formly throughout the seven seas ; if you then took a glass of
water anywhere out of the ocean, you would find in it about a
hundred of your marked molecules.
In the case under discussion, however, we are certainly
not dealing with a glass of organic substances but with
incomparably larger quantities. H. C. Urey has calculated
that, if only half the carbon now existing on the surface of
the Earth took the form of an aqueous solution of organic
substances, then the primaeval ocean would consist of a lo per
cent solution of such substances. (One must, of course, bear
in mind that the amount of water on the surface of the Earth
at that time was about one-tenth of what it is now.) There
is thus no question of such wide dispersal of organic com-
pounds in the waters of the primitive ocean or of such low
concentrations as to preclude the possibility of organic mole-
cules reacting with one another. On the contrary, even the
mean concentrations were very high, quite sufficient for the
later development of more and more complicated and diverse
carbon compounds by polymerisation and condensation.
SOURCES OF ENERGY 187
Furthermore, the hydrosphere ot the Earth was no more
uniform then than it is now. In isolated parts of it, such as
land-locked basins of shallow water, gulfs or lagoons, evapora-
tion of water might have led to even higher concentrations
of organic substances. Local increases in concentration could
easily have been brought about by the adsorption of organic
substances on clays or other inorganic deposits on the bottom
and shores of the water as was suggested by J. D. Bernal in his
well-known book The physical basis of life.^^'^
Some authors, such as V. Vil'yams^^" and N. Kholodnyi,^'*^
have even taken the view that the chemical processes leading
up to the appearance of life did not take place in the seas
and oceans but on the surfaces of particles of marl derived
from the primary mineral formations. B. B. Polynov,^^^ who
was very interested in questions concerning the migration
of the elements within the biosphere, also held this view.
We must, however, emphasise most strongly that it was
the actual water of the hydrosphere which formed the neces-
sary medium in which arose the very complicated organic
compounds which later provided the material for the forma-
tion of the bodies of living things. Even now water forms
the predominant, though also the simplest, chemical com-
ponent of all ' living matter ' of the whole range of organisms
inhabiting the Earth.
The complicated interactions of organic substances, their
synthesis and degiadation in living organisms, can only take
place in an aqueous medium and the water itself plays a
direct part in these processes. Whenever the water content
of a living body is substantially decreased there occurs either
complete destruction of that body or else anabiosis, the tem-
porary suspension of metabolism.
Even if we adopt the hypothesis of Vil'yams and Kholodnyi
that the processes of transformation of organic substances
took place on the surfaces of mineral particles, it is still
necessary to assume the presence of water on these particles,
if not as droplets, at least in the form of a surface film. Only
under these conditions could there have taken place the
formation of complicated organic compounds such as exist
at present. This is to say that the situation on the particles
is similar to that in the water of the hydrosphere though,
l88 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
on the particles, the water does not exist in large basins but
is diffuse or subdivided.
Unlike these authors, we feel that it is far more probable
that the formation of complicated organic compounds
occurred mainly in the waters of the seas and oceans. These
occupied a large part of the surface of the Earth and there-
fore the bulk of the carbon compounds accumulated in them.
The presence of large basins of water also enabled the migra-
tion of the non-volatile elements to take place faster and more
completely. This led to the formation of a particular mixture
of inorganic substances, many of which played an essential
part in the transformation of carbon compounds as catalysts
and even as components of the material of which ' living
matter ' is constructed.
Vil'yams and Kholodnyi developed their hypotheses mainly
because they saw in the marl particles a protection for the
developing proteins against the disintegrative action of ultra-
violet radiation. However, at the stage of the development
of organic substances which we are now considering, the
action of the ultraviolet radiation might have played a
positive part, just as it did in the atmosphere. In the hydro-
sphere, however, this activity would be limited to the most
superficial layers because the ultraviolet radiations could not
penetrate deeper into the water.
Thus there must have accumulated in the primaeval
hydrosphere considerable amounts of oxygen-, nitrogen- and
sulphur-containing derivatives of hydrocarbons coming partly
from the lithosphere, but mostly from the atmosphere.
The further transformation of these derivatives was partly
brought about by ultraviolet radiations but mainly by cata-
lytic processes.
Among the catalysts taking part in these reactions there
may have been both salts in aqueous solution and also in-
soluble deposits on the surface of which the organic com-
pounds were adsorbed. The compounds which were formed
in the hydrosphere became more and more complicated and
it is therefore hard to imagine the whole course of the chemi-
cal processes which occurred there.
BIOCHEMICALLY IMPORTANT COMPOUNDS 189
The origin of carbohydrates, lipids, porphyrins,
amino acids, nucleotides, polynucleotides
and protein-like polypeptides.
We shall confine ourselves to an attempt to draw a possible
picture of the formation of only some isolated groups of
organic substances of the greatest biological significance :
carbohydrates, some lipids, organic acids, porphyrins, nucleo-
tides and, finally, protein-like substances.
However, before turning to this stibject we must discuss
briefly a phenomenon ^\ hich is characteristic of many organic
substances of biogenic origin, namely their dissymmetry^*^
and the possible ways in \vhich this could have arisen on the
Earth before the appearance of life.
The gradual increase in the complexity of organic sub-
stances which occurred during their evolution led, at a par-
ticular stage in their development, to the emergence of a
new property, the dissymmetry of molecules. This property
appears whenever an increase in complexity of the molecule
leads to at least one of its carbon atoms being united through
each of its four valencies to different groups of atoms. For
example neither methane, nor carbon monoxide, nor the acet-
aldehyde which was formed from them, nor even acetic acid
possessed this property, in that three of the valencies in their
methyl groups were satisfied in the same way, with hydrogen.
Neither does dissymmetry arise when glycine is formed by
substituting an amino group for one of the hydrogen atoms
in acetic acid. However, when another hydrogen atom is
replaced by a methyl group with the formation of alanine,
dissymmetry arises. This property of molecules is expressed in
the existence of two very similar forms of the given organic
substance ; their molecules contain exactly the same atoms
and even exactly the same groups, but these groups are differ-
ently disposed in space. If a particular radical is on the right
in one of the forms it will be on the left in the other and
vice versa. Our two hands serve as a simple model of this
dissymmetry. If we lay them side by side with the palms
down we shall see that, for all their similarity, the right and
left hands are radicallv different in the arrangement of their
separate parts. If the thumb is on the left of the right hand,
a b
Fig. 13. Crystals of [a) laevo- and
{h) dex<ro-quartz.
190 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
the thumb Avill be on the right of the left hand, etc. Thus
each hand is the mirror image of the other (Fig. 13).
In the ordinary labora-
tory synthesis of organic
substances we always obtain
mixtures of equal parts of
both forms of dissymmetric
molecules (a so-called race-
mate). This is easy to under-
stand, because the formation
of one form or the other
(the dextro or laevo anti-
pode) in a chemical reaction
depends on which of two
atoms, placed on one side or
the other of the plane of symmetry, will be replaced by a new
group of atoms. But the very concept of symmetry implies
that both of the atoms in question are subject to identical
forces. The probability that one antipode or the other will
be formed is therefore exactly the same. Such large numbers
of molecules take part in these chemical reactions that statisti-
cal laws apply to them and it is very unlikely that an excess of
one or other antipode will arise. Indeed we do not usually
observe such an excess under natural conditions in the absence
of life, or in laboratory syntheses."* In Miller's experiments,
for example, when he used silent electric discharges, alanine
and the other amino acids always appeared in the racemic
form.
In living organisms, on the other hand, the amino acids
of which the natural proteins are formed are exclusively in
the L configuration. The d forms of amino acids are to be
found for certain only in some specific bacterial or fungal
products, particularly in antibiotics (e.g. D-leucine in grami-
cidin"^ and D-phenylalanine in tyrocidine"®). In such cases,
however, the l forms of these acids usually are absent.
As a general rule, if a substance having dissymmetric
molecules is elaborated by a particular organism, that organ-
ism will only produce one of its two forms. The antipode of
that substance is either not to be found in living things, or
else it is produced by some other organism. This rule applies
BIOCHEMICALLY IMPORTANT COMPOUNDS KJl
particularly to substances which are o£ importance for life,
such as the amino acids, proteins, carbohydrates, certain
lipids, etc.
This capacity of protoplasm to form and store only one
antipode of dissymmetric molecules is an indication of the
asymmetry of living substance. It is absent from non-living
nature but is a characteristic feature of all living things. ^'^^
The fact was noticed by L. Pasteur^*^ who wrote of it as
" this great character which establishes perhaps the only well
marked line of demarcation that can, at present, be drawn
bet^veen the chemistry of dead matter and the chemistry of
living matter ". The same idea was later emphasised by V.
Vernadskir*^ who thought that the chemical non-identity of
the dextro and laevo forms ^vithin living bodies was due to
the presence of a peculiar ' configuration of cosmic space '
in these bodies which cannot be reproduced under laboratory
conditions. However, a large body of evidence has since
been obtained, which shows conclusively that dissymmetry
can arise independently of life.^^"
Pasteur himself^" had already pointed out the ways in
which the formation of dissymmetric substances might have
been achieved in nature. In his opinion this could occur
in the presence of some other dissymmetric substance or as
a result of the action of some asymmetric physical factor.
The first part of this hypothesis w^as later developed by E.
Fischer^^^ in its application to the synthesis of the higher
sugars. In increasing the number of carbon atoms in a sugar
molecule by the cyanhydrin synthesis, E. Fischer showed that
the presence of a particular configuration in the original
molecule of sugar affects the form of the derivative, and. of
the two possible configurations which could result from the
entry of the new carbon atom into the compound, only one
actually arises. Fischer put forward the hypothesis that the
dissymmetry of carbohydrates and other substances in living
cells arises because they are synthesised within organisms
under the influence of optically active substances such as
chlorophyll.
W. Marckwald^^^ confirmed this hypothesis experimentally.
He obtained an optically active (dissymmetric) substance by
using in its synthesis a substance which is already dissymmct-
192 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
ric, the alkaloid brucine. Marckwald combined the brucine
with methylethylmalonic acid, which is not dissymmetric
as two of the valencies of its a carbon atom are occupied by
carboxyl groups. When the resulting compound was de-
carboxylated only the free carboxyl group (that which was
not combined with brucine) was split off. When the brucine
was later removed leaving methylethylacetic acid, this was
dissymmetric with a definite preponderance of the laevo
isomer.
COOH COOH H
\_ \_ _\_
/ / . /
COOH COOH — brucine gooh
A. McKenzie^^* later used the same method for carrying
out a whole series of dissymmetric syntheses. Thus, if we
have dissymmetric substances at our disposal, we can use
them to obtain other dissymmetric substances. From this
point of view special interest attaches to the work of the
school of G. Bredig^" on dissymmetric syntheses with the
help of catalysts, among them dissymmetric substances.
For example, G. Bredig and M. Minaeff^^*^ showed that if
the chemical combination of hydrocyanic acid with aldehydes
is brought about by the catalytic activity of quinine or quini-
dine, then, in the one case the dextro and in the other the
laevo form of cyanhydrin is obtained. The catalysts of living
cells, the enzymes, are dissymmetric. Synthesis brought about
by them must, therefore, also lead to the formation of dis-
symmetric compounds. Such syntheses have, indeed, been
carried out by many workers, especially C. Neuberg^" in his
work on the dehydrases, carboligase, aldehyde mutase and
other enzymes of yeast.
In living cells the differential adsorption of the different
antipodes on structures composed of dissymmetric materials
may play an important part. Under laboratory conditions
separations of this kind can be carried out on paper or
silica gel containing an optically active substance (camphor-
sulphonic acid, mandelic acid, etc.y'^^ or in other ways.
Thus it is now to some extent clear in principle in what
BIOCHEMICALLY IMPORTANT COMPOUNDS 193
way dissymmetry develops within living organisms. It is true,
as W. Kuhn^^^ has already pointed out, that the simple laws
of dissymmetric synthesis are not sufficient to explain the
extremely high degree of optical purity found in protoplasm
and the constancy with which it is maintained throughout
innumerable generations of organisms. There can, however,
no longer be any doubt that particular antipodes are formed
in living things as the result of the presence of pre-formed
dissymmetric substances, especially dissymmetric enzymes.
Furthermore, this asymmetry is enhanced by the character-
istic specific organisation of protoplasm which we shall discuss
in more detail later on.
This explanation of the appearance of dissymmetry in
protoplasm does not, however, get over the problem of the
original dissymmetric synthesis, for all the syntheses discussed
so far have depended on the presence of pre-formed dis-
symmetric compounds which are usually derived from plants
(e.g. brucine and quinine).
This question was raised very pointedly by F. R. Japp^''"
at the turn of the century. In his paper Stereochemistry and
vitalism Japp categorically denied the possibility of primary
dissymmetric synthesis and declared that optical activity
could only arise with the help of the ' life force '. Like a
living being, an optically active molecule can only arise
from another of the same kind. Dissymmetry never arises
primarily outside a living organism.
This assertion turned out to be untrue, in that dissym-
metric substances can arise, not only in the presence of other
dissymmetric substances, but also under the influence of
dissymmetric physical factors. As we have already pointed
out, Pasteur^" had already had this very idea. He considered
that the formation of optically active compounds in nature
occurred under the influence of ' dissymmetric forces ' asso-
ciated with the movement of the Earth, terrestrial magnetism,
etc. With this in mind Pasteur tried to obtain optically active
substances by carrying out reactions in rapidly rotating tubes
or by allowing racemic mixtures to crystallise in a strong mag-
netic field. Pasteur did not obtain positive results by these
experiments. It was shown later by P. Curie"^ that this lack
of success was due to the fact that the influences applied by
13
194 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
Pasteur were not, in fact, dissymmetric. Pasteur's experi-
ments were based on a false conception of the asymmetry o£
motion and magnetic fields. His idea was, however, funda-
mentally sound.
As early as the end of the nineteenth century J. H. van't
Hoff^" pointed to the circular polarisation of light as a
possible cause of the appearance in nature of dissymmetric
substances formed photochemically. For a long time attempts
to confirm this idea experimentally did not meet with posi-
tive results because those who performed them did not take
account of the condition " that one should choose only those
reactions which can usually be initiated by the action of the
waves of light ".^**
Success was first obtained in 1929 by W. Kuhn and E.
Braun,^^^ who decomposed a racemic ester of a-bromopropri-
onic acid under the influence of circularly-polarised ultra-
violet light with a wavelength of 2,800 A. These experiments
showed that it is possible to obtain an optically active sub-
stance from an inactive one without any participation by
organisms or products derived from them. In these experi-
ments, however, as in many later ones (W. Kuhn and E.
Knopf,^" S. Mitchell,^" J. C. Ghosh,"« and others) the
optical activity did not, strictly speaking, arise as the result
of the synthetic process but was due to the fact that the
antipodes making up the racemic mixture decomposed at
different rates under the influence of the polarised light.
The direct synthesis of a dissymmetric substance by irradia-
tion with circularly-polarised light was first accomplished
by G. Karagunis and G. Drikos^*^ and later by a number of
other workers.
The synthesis by T. L. Davis and J. Ackermann"" is
specially interesting to us. By irradiating completely optically
inactive original materials with right circularly-polarised
ultraviolet radiation (2,535 " 2,539 A) these authors obtained
a substance, tartaric acid, as the very antipode which is
widely distributed among living things.
It may now be held that we have complete proof of the
presence of circularly- or elliptically-polarised light under
natural conditions. This was already established by A. Byk^^^
and has since been fully confirmed. For example, the light
BIOCHEMICALLY IMPORTANT COMPOUNDS 195
of the sky is partly plane polarised but on reflection from
water it becomes elliptically polarised. Thus, many causes
work together to bring about the presence of right ellipti-
cally-polarised light on the surface of the Earth.
Thus we now have some basis for supposing that the action
of circularly- or elliptically-polarised light (especially ultra-
violet light) must have led to the appearance of dissymmetric
substances in the atmosphere and hydrosphere of the Earth
even before the emergence of life.
We must point out another possible way in which dis-
symmetric substances could have been formed without the
participation of living things, namely by using dissymmetric
crystals as catalysts. The possibility of using this method for
the synthesis of dissymmetric substances in the laboratory
was noted by I. Ostromisslensky^'^ as early as igbS. However,
it was not until the 1930s that this idea was realised practi'
cally in the experiments of G.-M. Schwab and his collabora-
tors'^^ and in the analogous experiments of A. Stankewitch.'"^
G.-M. Schwab succeeded in obtaining an optically active
substance by partial destruction of its racemate in a reaction
catalysed by metals deposited in a thin coat on dextro- or
laevo-quartz crystals.
Such quartz crystals are ^videly distributed in inorganic
nature. J. D. Bernal,'" therefore, put forward the hypothesis
that the dissymmetry of organic substances might have arisen
primarily, before life appeared on the Earth, as a result of
the synthesis of these compounds on the surfaces of quartz
crystals which adsorbed the starting materials. It is true that
in Schwab's experiments it was not synthesis but decomposi-
tion which took place. Recently, however, some Soviet chem-
ists, in the first place A. Terent'ev and his colleagues,"^
have succeeded in carrying out the direct dissymmetric syn-
thesis of a number of organic compounds by using catalysts
deposited on powders made from crystals of dextro- or laevo-
quartz. From our point of view the most interesting reactions
are the aldol condensations and the reaction of cyanethyla-
tion, which occur by quartz catalysis in the liquid phase and
at ordinary room temperatures.
In conclusion, we shall mention a few cases of the spon-
taneous development of dissymmetry from optically inactive
igG ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
Starting materials in an enclosed system without the partici-
pation of any dissymmetric auxiliary substance whatsoever.
C. Neuberg^" kept a specimen of the potassium salt of P-
methylvaleric acid for some years. During this time it par-
tially crystallised. When the crystals were separated from it,
the mother liquor was found to have considerable optical
activity. Another similar case has been described by E.
Havinga^^* who kept a solution of methylethylallylphenyl-
ammonium iodide in a sealed tube for two months and found
that optically active crystals with a considerable specific rota-
tion had separated out ([a]D + 27° in chloroform). In a later
publication Havinga"^ discussed the idea that even long
before the appearance of life there might have occurred on
the Earth similar spontaneous dissymmetric syntheses of
various organic compounds.
Thus, in contrast to the pessimistic utterances of the turn
of the century, we now know of several ways by which opti-
cally active carbon compounds might have arisen primarily
on the Earth before the appearance of life. In our further
discussion we shall try to show what were the causes which
led to the fixing in protoplasm of the dissymmetry of organic
molecules which had arisen primarily, and what an essential
part this played in the general organisation of living things.
Let us now turn to a consideration of what may be said
about the primary formation of the groups of compounds
most characteristic of life in the waters of the primaeval
ocean. We have a wide range of factual material obtained
from laboratory experiments relating to this matter. This
shows that the immediate oxygen, nitrogen and sulphur
derivatives of hydrocarbons, when dissolved in water in the
presence of various inorganic catalysts or adsorbed on clay
or other precipitates, cannot remain unchanged even at the
comparatively low temperatures which are common under
present conditions.
By reacting with each other and with molecules of water
they undergo many of the reactions which occur by simply
allowing the solutions to stand in the laboratory, but which
may also be observed occurring as stages in the metabolism
of living organisms. There take place in the laboratory the
reactions of oxidation and reduction, aldol condensation,
BIOCHEMICALLY IMPORTANT COMPOUNDS 197
polymerisation, ring formation and the migration of radicals.
In living things, however, these reactions are strictly co-
ordinated in respect of their velocities so that they form a
long chain of processes in which one reaction follows the
other in a strictly determined sequence. As a result of this,
it is a general rule that not all the transformations which
are thermodynamically possible in the organism actually
occur there. Only strictly determined synthetic pathways are
followed and therefore highly specialised compounds are
formed. The reactions are also so completely harmonious
that they can be combined in such a way that the energy
liberated by one reaction can be used for another which
could not take place spontaneously without it.
Such co-ordination can, however, only occur in very highly
developed and well-organised systems (such as Organisms)
and not simply in a solution of various carbon compounds.
Any co-ordination which may occur in these, if indeed any
does, is a purely temporary and fortuitous phenomenon and,
as a rule, the only reactions which take place are those in
which the compounds participating are themselves rich in
free energy or receive supplementary energy from quanta
of light, electric discharges, increased pressure, etc. Con-
sequently, in the chaos of different and often mutually
independent transformations, there is a predominance (some-
times temporary and short-lived) of those reactions which,
under the given physico-chemical conditions and, above all,
in the presence of particular catalysts, occur fastest.
Unfortunately we cannot bring direct observation to bear
on processes of this sort under natural conditions. This is
prevented, not only by the oxidised conditions of the present
age, but even more by the ubiquitous distribution of living
things on the surface of the Earth. In their presence it is
very hard to differentiate between the abiogenic processes
which were possible in the primitive hydrosphere and the
biogenic ones which only occur at the present time. Organ-
isms confuse the whole issue in this respect. They discharge
into the surrounding inorganic medium large amounts of
specific substances which can only be formed in the course of
highly organised metabolic processes and which are most
unlikely to have been formed under primaeval conditions.
igS ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
On the other hand, organisms can absorb and consume such
substances, and metaboHse them to form parts of their own
bodies. They radically alter the whole course of the chemical
processes in their environment, not merely by their own
immediate activities, but also by means of the extremely
powerful catalysts which they produce — enzymes.
We can therefore only judge of the transformations accom-
plished by the more or less complicated organic compounds
on the Earth at some time before the appearance of life by
analogy with phenomena which have been observed by arti-
ficially set up laboratory experiments.
It is very easy to imagine the abiogenic development of
sugars and carbohydrates generally in the primaeval hydro-
sphere. The well-known synthesis carried out by A. But-
lerov"" as early as 1861 may serve as the starting point for
this.
If one simply allows a solution of formaldehyde in lime
water to stand under ordinary laboratory conditions, con-
densation occurs and one obtains a syrup containing a sugar-
like substance which Butlerov called ' methylenitan '. The
chemical nature of this substance was not elucidated until
thirty years later. By similar means E. Fischer and J. TafeP"
prepared a syrup containing a mixture of sugars and isolated
from it a hexose (CeHiaOe) which they called ' acrose '. This
was optically inactive, as was to be expected from a labora-
tory synthesis. This optical inactivity was, however, merely
due to the fact that acrose was a racemic mixture of two
antipodal ketoses, natural D-fructose and L-fructose, its anti-
pode which is not met with in living nature. For this con-
densation reaction E. Fischer gave the following schematic
equation:
CHnO + CHoO -1- CHoO + CH2O -fCHsO + CH^O-^
CHoOH.CHOH.CHOH.CHOH.CO.CH.OH
However, it was later shown that the reaction seems to pass
through successive stages with the formation of intermediate
compounds containing fewer formaldehyde residues, in par-
ticular glvceraldehyde and dihydroxyacetone.
By slightly altering the conditions of Butlerov's experi-
ment O. Loew^*^ first obtained ' formose ', a sweet syrup
BIOCHEMICALLY IMPORTANT C0M;P0UNDS IQQ
which is not fermented by yeasts, and then ' methose ', a
syrup which on dilution undergoes fermentation, i.e. it
contains a sugar which can provide nourishment for hetero-
trophic organisms. E. Fischer and F. Passmore^^^ showed
that ' formose ' and ' methose ' contained a and /3 ' acrose '
(DL-fructose and DL-sorbose). H. and A. Euler^*'* observed
the condensation of formaldehyde in aqueous solution in the
presence of calcium carbonate. In this way they obtained,
among a number of other products, glycolic aldehyde, which
was formed by the aldol condensation of two molecules of
formaldehyde
HCHO + HCHO^CHoOH.CHO
Experiments by Fischer and others^^^ showed that succes-
sive aldol condensations of glycolic aldehyde gave rise to
tetroses and hexoses. However, in their experiments the
Eulers found DL-araboketose, which had evidently been
formed by the condensation of glycolic aldehyde and glycer-
aldehyde.
As E. Schmitz^^^ showed, glyceraldehyde condenses in the
presence of calcium or barium hydroxide to give fructose
and sorbose. In this reaction part of the glyceraldehyde is
first converted into dihydroxyacetone and this then combines
with the remaining glyceraldehyde to give a hexose. It was
later^" established that condensation of glyceraldehyde and
dihydroxyacetone leads to the formation of hexoses, whereas
condensation of glycolic aldehyde and glyceraldehyde gives
rise to pentoses.
There has now accumulated in the scientific literature a
very large amount of material concerning the formation of
sugars and their derivatives in the way indicated above. ^*®
Such reactions have even been used for the production of
sugars on a technical scale. "^
All the conditions necessary for the spontaneous formation
of sugars were present in the primaeval hydrosphere — the
starting materials in the form of various aldehydes and
ketones, the catalysts in the form of lime, chalk, etc.
Thus we have very good reason to suppose that sugars,
compounds which play a very important part in metabolism
both as sources of energy and as structural materials for living
200 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
things, arose primarily in the waters of the surface of the
Earth long before the appearance of life on it.
Like glycolic aldehyde, acetaldehyde can also undergo
condensation and we have already shown that acetaldehyde
must have been produced in the primaeval atmosphere by
the interaction of methane and carbon monoxide. When this
condensation occurs, aldol is formed, which can easily iso-
merise to give butyric acid.
2 CH3.CHO->CH3.CHOH.CH2.CHO-> CH3.CH2.CH2.COOH
Further condensation of aldol into more complicated pro-
ducts was found by S. M. Losanitsch and M. Z. Jowitschitsch
in an oily liquid which they obtained from acetaldehyde:
n CH3.CHOH.CH2.CHO^ (CH3.CHOH.CH2.CHO)„
and further isomerisation of these products revealed one of
the possible methods of formation of the higher fatty acids.
Under somewhat difiFerent conditions crotonic condensa-
tion of acetaldehyde takes place :
CH3.CHO-}-CH3.CHO->CH3.CH : CH.CHO -j- H2O
The crotonaldehyde in its turn can condense with one
molecule of acetaldehyde giving rise to sorbic aldehyde:
CH3.CH : CH.CHO-}-CH3CHO->CH3.CH : CH.CH : CH.CHO-I-H2O
This can condense further :
CH3.CH : CH.CH : CH.CHO + CHa.CHO^
CH3.CH : CH.CH : CH.CH : ch.cho + HsO, etc.""
This is a method of synthesising polyenes, compounds with
conjugated double bonds ; that is to say, it is a way of syn-
thesising lipids like carotene, vitamin A and others which
are very important biologically and very widely distributed
throughout living nature.
J. D. BernaP'^ has recently put forward the opinion that
the lipids must have arisen at a comparatively late stage in
organic chemical evolution. It seems to me that, on the
contrary, the reduced conditions on the surface of the
primaeval Earth were especially favourable for the formation
BIOCHEMICALLY IMPORTANT COMPOUNDS 201
of hydrophobic compounds of high molecular weight which
are rich in hydrocarbon groups.
The process of the formation of petroleum, which is going
on at present at considerable depths, and therefore under
anaerobic conditions, to some extent confirms this idea.
Direct experiments on the synthesis of individual lipids
analogous to those of Miller with amino acids have, un-
fortunately, not yet been carried out under conditions which
reproduce the state of the primaeval surface of the Earth.
Our knowledge of the primary formation of lipids is there-
fore still very scanty and unreliable. It is considerably more
meagre than what we have in respect of carbohydrates.
Most contemporary authors dealing with the problem of
the origin of life affirm Tvith complete conviction that at
some stage in organic-chemical evolution in the waters of
the primaeval ocean there must have occurred the primary
development of those biologically important heterocyclic
compounds, the porphyrins. These assertions are, however,
usually of a very general nature and have but little experi-
mental corroboration.
Only recently, and mainly thanks to the work of D.
Shemin"^ and others, has there been a great increase in our
knoAvledge of the biosynthesis of porphyrins in living organ-
isms. Shemin showed that the starting substances in this
synthesis were fairly simple compounds, glycine and succinic
acids, i.e. substances which could undoubtedly have arisen
from the simpler hydrocarbons, ammonia and water. How-
ever, the actual process of biosynthesis takes place in many
stages and requires for its accomplishment the presence of
a very highly organised living system containing numerous
enzymes and intact protoplasmic structures.
In this synthesis the succinic acid must first be activated.
In the living cell this is brought about by taking it into
the succinic acid-glycine metabolic cycle. In this, succinyl-
coenzyme A is formed and condenses with the a carbon atom
of glycine and in this way a-amino-^-oxoadipic acid is formed.
It must be noted that the condensation of succinate with
202 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
glycine is only possible in the presence of intact protoplasmic
structures.
By decarboxylation a-amino-^-oxoadipic acid is converted
into 8-aminolaevulinic acid:
HOOC.CH2.CH2.CO.CHNH2.COOH->HOOC.CH2.CH2.CO.CH2NH2 + CO2
On condensation, two molecules of 8-aminolaevulinic acid
form a pyrrole, porphobilinogen. Four molecules of porpho-
bilinogen give a porphyrin structure which, by decarboxyla-
tion and dehydrogenation of the side chains forms proto-
porphyrin.
It must be remarked that each link in this chain of chemi-
cal transformations requires a specific enzyme. However J. J.
Scott^^^ has recently succeeded in demonstrating the possi-
bility of converting 8-aminolaevulinic acid into porphobilino-
gen by purely chemical (not biological) means. In the course
of this work he established that this reaction is not peculiar
to 8-aminolaevulinic acid but can be undergone by a-amino-
ketones in general, with the formation of a-aminomethyl-
pyrroles. In addition to this A. Treibs"^ says that the trans-
formation of porphobilinogen into a mixture of porphyrins
can also be achieved abiogenically at high temperatures and
acidities.
Certainly it is hard to tell at present to what extent
analogous processes could have taken place under natural
conditions independently of organisms.
As we have seen above, a number of workers have done
many experiments in which pyrrole and pyrrolidine were
easily formed from ammonia, acetylene and other unsatur-
ated hydrocarbons by simple catalysis or under the influence
of ultraviolet radiations. The development of these hetero-
cyclic compounds in the primaeval atmosphere or hydro-
sphere can therefore scarcely be doubted. However, the
possibility of their combination there to form porphyrin
nuclei still needs to be substantiated. The porphyrins of
petroleum which have been found under natural conditions
are clearly of biogenic origin. They remained in the pet-
roleum after the decomposition of the organisms which had
synthesised them when alive.
BIOCHEMICALLY IMPORTANT COMPOUNDS 203
The question of the possibility that amino acids might
have been formed under conditions similar to those which
prevailed in the primitive hydrosphere has recently been
studied by S. Fox/®^ He showed that in a medium resembling
a natural hot spring (an aqueous medium containing calcium
salts at pH 80 - 90 and at a temperature of 100 - i20°C) the
interaction of malic acid and urea gives rise to the formation
of aspartic acid and, what is specially interesting, to ureido-
succinic acid.
We must now turn our attention to the question of the
possibility of the primary abiogenic formation of nucleosides
and nucleotides, in view of the extremely important part
played by polynucleotides and, in particular, nucleic acids
in the vital processes of organisms. As concerns the possi-
bility of the formation of pyridine from acetylene and hydro-
cyanic acid Berthelot established the following equation:
H
CH KC^ CH
2 III +HCN^ I II
CH HCy yCH
According to the results of Chichibabin, Ishigura, Ellis
and others, pyridine and pyrimidine bases can easily arise
from ammonia and unsaturated hydrocarbons.
Urea can also serve as the starting substance for the prim-
ary formation of pyridine and pyrimidine bases, and the
urea itself can arise either from ammonium cyanate (as in
Wohler's synthesis) or, as we have already shown, by the
combination of carbon monoxide and ammonia in silent
electric discharges.
The first synthesis of uric acid was carried out as early as
1882 by I. Gorbachevskii by heating urea with glycerine.
Numerous syntheses of purines and pyrimidine bases have
been brought about by the condensation of urea with organic
acids. For example, uracil was obtained by D. Davidson and
O. Baudisch^'*^ by condensing urea with malic acid. An
204 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
intermediate compound in this reaction is /5-hydroxyacrylic
acid which is formed from the malic acid
NH» COOH NH — CO
II 11^
CO + CH -> OC CH + 2H2O
I II I 11
NHg HCOH HN — CH
urea j8-hydroxyacryHc acid uracil
Uric acid can be synthesised by the method of R. Behrend
and O. Roosen^^^ from urea and mesoxalic acid:
NH, COOH CO — NH CO ^NH NH — CO NH2
II II 1 I I I I
CO + CO -> CO CO + Ho ^ HCOH CO -> CO COH + CO
II II I I 1 II I
NH2 COOH CO — NH CO NH NH— COH NH2
ureamesox- alloxan dialuricacid isodialuric acid
alic acid
NH CO
I I
-> CO C— NH+ 2H2O
>CO
NH — C — NH
uric acid
Under reducing conditions, uric acid may be converted
to various purine bases/^' In connection with the possibility
of the primary formation of nitrogen-containing heterocyclic
compounds the work of H. Staudinger and K. Wagner"^ on
the products of the condensation of urea with formaldehyde
is very interesting.
Recent work using marked atoms has shown, however,
that the synthesis of purines and pyrimidines in the living
organism occurs in a different way.^°° It is not based on
urea^" as was thought earlier, but proceeds by the combina-
tion of formyl residues with ammonia and oxaloacetic acid
or with glycine. ^"^
BIOCHEMICALLY IMPORTANT COMPOUNDS 205
It has also been sho^vn that when nucleosides are formed
in protoplasm it is not pre-formed purines and pyrimidines
which combine with the pentoses, but the much simpler
compounds Avhich we have already mentioned, which serve
as the starting materials for their formation. ^"^
Of course one must be very careful here, as in all other
cases, in drawing analogies between what happens in the
living organism and what might have taken place in the
waters of the primaeval ocean. Nevertheless we can construct
on this basis hypotheses, though only very rough ones, about
the primary formation of nucleosides, as the ribose or desoxy-
ribose required can be produced in the ways which we have
described for other carbohydrates.
The possibility of the incorporation of the third com-
ponent of nucleotides, orthophosphoric acid, at first glance
presents no difficulties. The question of the primary, abio-
genic formation of compounds of phosphorus with organic
substances is, however, extremely complicated and poorly
understood.
In the powerfully reducing conditions which prevailed on
the surface of the Earth in the earliest epoch of its existence,
when carbon, nitrogen and sulphur w^ere present in the forms
of methane, ammonia and hydrogen sulphide, phosphorus
must also have entered into the primitive atmosphere, though
only in part, in the form of hydrogen phosphide, which
reacted with the hydrocarbons to form substituted phos-
phines.
Unfortunately we only have very old and extremely
general information to the effect that the action of electric
discharges on mixtures of phosphine and ethylene leads to
the occurrence of extensive condensation reactions.^"* Changes
of this kind can also come about on ultraviolet irradiation,
for phosphines absorb radiations having wavelengths in the
region of 2,315-2,290 A. In the outer layers of the atmo-
sphere, however, the phosphines must have been oxidised
by the oxygen derived from the photolysis of water with the
formation of phosphine oxides and alkylphosphinic acids. ^°^
This may be regarded as the formation of phosphorous acid
2o6 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
in which an alkyl group has been substituted for one of the
hydrogen atoms.
R\
R — P + O -^ R P =
R'^ R-^
0
H
0
R — P<f + 30 ->
^H
R — P — OH
0
According to N. N. Semenov^"® hydrogen phosphide can
be oxidised directly by oxygen, the reaction proceeding by
the following stages
PH3 + 0
-^
PH + HgO
PH + 02
— >
HPO + 0
HPO + O2
— >
HP< >0
^0^
HP< No + PHo
_^
PH + H3PO.
Phosphorous acid is formed in this way and gives rise to
the corresponding salts, the phosphites.
While studying the physico-chemical environment which
was formed by the reducing conditions of the primaeval
hydrosphere A. Gulick^"^ recently came to the conclusion
that its waters must have contained dissolved phosphites
rather than orthophosphates, as had been the commonly
accepted belief. Under these conditions orthophosphates
would have been almost completely insoluble. Gulick points
out that even now the amount of phosphorus dissolved in
sea water is only 12 parts in 10® by weight. By contrast the
solubility of phosphite and hypophosphite (caHPOs and
Ca(H2P02)2) in water is comparatively great. These, however,
can only persist under reducing conditions.
Starting from cyanamide (which very probably developed
BIOCHEMICALLY IMPORTANT COMPOUNDS 207
in the primaeval atmosphere) and ammonium phosphite,
Gulick postulates the following series of reactions
H H
HgNC^N -}- H4N — O — P — OH »■ HgN C NH — O — P — OH
O NH O
cyanamide ammonium guanidine
phosphite phosphite
OH
I
I
-^ HgN — C NH P — OH
II II
NH O
phosphoguanidine
Thus there are obtained high-energy compounds which
could have arisen under the conditions of the primaeval
ocean. These compounds are similar to phosphocreatine,
which plays an important part as a reservoir of free energy
in muscle metabolism.
Unfortunately Gulick's paper does not give any experi-
mental support for the possibility of the transformation
of guanidine phosphite with an energy of phosphorylation
of about 2000 - 3000 cal. into phosphoguanidine with an
energy of phosphorylation of about 12,000 cal. The author
only points out in a very general way that photochemical
energy or the energy of concurrent exothermic reactions could
serve for the carrying out of these reactions. But this is just
what needs to be proved. It would therefore be very desirable
to have direct experiments to substantiate the possibility that
phosphoguanidine or some other high-energy compound
could be formed under the conditions which existed on the
surface of the primaeval Earth, for the formation of sub-
stances of this sort in the primitive ocean would have been
an extremely important event.
In his well-known book Time's arrow and evolutiorf°^ H.
Blum states explicitly that in his opinion the appearance
within the complicated mixture of primary organic sub-
208 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
Stances of high-energy phosphorus compounds such as adeno-
sine triphosphoric acid (ATP) was the decisive event deter-
mining the transition from the inanimate to the animate
state. In this he is starting from the hypothesis that the
adenylic acid systems which were developed primarily and
which are now widely distributed in living nature would,
under the conditions present in the primitive ocean, open
up the possibility of the formation of proteins, inasmuch as
the energy required for the synthesis of polypeptides is com-
paratively small and could be provided at the expense of a
single high-energy bond. Blum considers that an adenylic
system could also have formed the basis for the development
of nucleic acids.
The author himself admits that the details of the process
\vhich he has put forward are very vague, and he bases his
opinion solely on the phenomena which take place in living
things. It does, indeed, seem more and more probable that
the energy needed for the synthesis of the polypeptide bonds
of protein molecules is provided in the living organism
through the agency of high-energy phosphorus compounds.^"'
In particular, according to H. Borsook^^" the first stage in
this synthesis is the activation of the carboxyl groups of free
amino acids at the expense of ATP, either directly or through
coenzyme A. The synthesis of nucleic acids in living proto-
plasm takes place in just the same way, at the expense of
high-energy bonds. In this process, according to H. M.
Kalckar^^^ phosphorylated ribose (ribose - 1 - phosphate) ex-
changes its phosphate radical for a purine or pyrimidine
base with the formation of the corresponding nucleoside. ^^^
However, R. Zahn^" considers that first there must sud-
denly have been formed polyphosphoric acid, which is even
now present in a number of organisms. ^^*
Starting from this assumption and proceeding by analogy
with the reactions which occur in living things, L. Roka^^^
has drawn the following hypothetical picture of the forma-
tion of nucleic acid in the waters of the primaeval ocean :
the macromolecule of polyphosphoric acid which arose there
reacted with glyceraldehyde to form polyglyceraldehyde phos-
phate, which, in later reactions, combined with acetaldehyde.
This scheme is based on the observation of the biosynthesis
BIOCHEMICALLY IMPORTANT COMPOUNDS 209
of desoxyribose phosphate from acetaldehyde and glyceralde-
hyde phosphate by Escherischia coli.
The polydesoxyribose phosphate formed in this way com-
bined with ammonia, oxaloacetic acid, glycine and formyl
residues. Thus were formed the primaeval desoxyribose
nucleic acids (Fig. 14).
Even for the biosynthesis of nucleic acids in living organ-
isms Roka's scheme is certainly no more than a very ingenious
hypothesis. We must regard with even greater reserve the
analog)^ between it and the processes which might have taken
place in simple aqueous solution of various organic com-
pounds in the primaeval hydrosphere.
Let us suppose that we have demonstrated the possibility
that Gulick's phosphoguanidine or some other high-energy
compound could ha\e been formed on the surface of the
Earth under the influence of ultraviolet irradiation or at the
expense of the large amount of energy which is liberated
by the oxidation of substituted phosphines by oxygen. Even
so, the probability that the energy of the high-energy bonds
would be transferred particularly to the carboxyl groups of
amino acids or used for the special purpose of phosphorylat-
ing ribose or for the formation of polyphosphoric acid is
extremely slight under conditions of simple aqueous solution
of large numbers of organic compounds. This could only be
expected to occur regularly in the presence of pre-formed
organisms, which would lead to the strict co-ordination of the
different biochemical reactions in space and time. Such
organisation is inherent in protoplasm, but it cannot have
existed in the waters of the primaeval ocean, where the course
of events was solely determined by relatively simple thermo-
dynamic and kinetic laws.
It may be reckoned that we shall succeed in proving the
possibility of the formation of complicated polynucleotides
in the primaeval hydrosphere in accordance with these laws
either in the way described or in some other way. It still
does not follow in the least that a similar primary origin
was possible for nucleic acids identical with those which are
essential for present-day living organisms. These nucleic
acids are characterised by a strictly determined sequence
of mononucleotides in their polynucleotide chains and this
14
w
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X
o o
\ll
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go
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I a
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0—0—0=0
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cu-
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0—0—0—0
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+
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0—0—0—0
w" I I
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+
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0—0—0=0
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— o
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a a
0— 0— 0— c
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:> 0—0—0—0
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* a
BIOCHEMICALLY IMPORTANT COMPOUNDS 211
sequence is very thoroughly adapted to the performance of
the physiological functions which they carry out in the living
cell. Such a sequence is hardly likely to have arisen merely
from the action of the simple laws which we have hitherto
been discussing.
What has been said about the formation of nucleic acids
applies also to the primary synthesis of proteins.
The possibility that amino acids might have been formed
on the surface of the Earth before the appearance of life
received its theoretical foundation and experimental con-
firmation in such experiments as those of Miller. The ques-
tion of the polymerisation of amino acids to form polypeptides
is more complicated.
Under laboratory conditions this reaction may be carried
out by comparatively simple and extremely diverse methods.
For example, a-aminocaproic acid may be polymerised simply
by heating it.^" Polymerised amino acids are obtained by
the decarboxylation of :^-carboxy anhydrides in the presence
of a small amount of water^^^ and in other ways. All these
reactions take place in media containing only traces of water.
It follows that they could not take place under the conditions
prevailing in the primaeval atmosphere and hydrosphere of
the Earth. Simply allowing aqueous solutions of amino acids
to stand does not lead to any appreciable polymerisation, in
contrast to what happens when sugars are synthesised from
formaldehyde by Butlerov's method. This has a simple
theoretical explanation, in that amino acids cannot poly-
merise to form polypeptides without taking up free energy.
Calculations show that the formation of a single peptide
bond requires, on the average, about 3,000 cal/mole.^^*
Thus, in a homogeneous medium containing a suitable
catalyst the equilibrium constant for the synthesis of alanyl-
glycine, for example, from alanine and glycine, will only
be 001.
It has, however, been suggested comparatively recently
by K. Linderstr0m-Lang,^^^ that in the synthesis of large
peptides from amino acids and other peptides, the change
of free energy Af may be considerably less than 3,000 cal.
This suggestion has been confirmed experimentally by A.
Dobry, J. S. Fruton and J. M. Sturtevant.^^"
212 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
On the basis of his experiments J. S. Fruton^-^ has con-
cluded that the magnitude of Af depends on the nature of
the components taking part in the reaction and is, accord-
ingly, very variable, sometimes falling at low as 400 cal/mole.
Most syntheses of peptides are endoergic but in certain cases
they may be exoergic. Furthermore, Fruton points out that
a very promising way of increasing the yield of peptides is
by using reactions which lead to the formation of products
which separate out from the general solution by becoming
insoluble. This is what happens when, for example, glycina-
mide is converted to glycine anilide. In this reaction the
yield may be as high as 65 per cent. Fruton considers that
one of the fundamental ways in which the length of poly-
peptide chains may be further increased is by transpeptida-
tion and transamination reactions which occur without the
expenditure of much energy.
In the scientific literature there have already accumulated
a number of more or less probable hypotheses as to the
sources of the energy needed for the synthesis of polypeptides
and the scheme of co-ordination of the energy exchanges in
the reactions. We may cite as an example the hypothesis
of F. Lipmann^^^ concerning the participation of trans-
phosphorylation of ATP, which is based on experiments
on the synthesis of glutathione. However, as we have pointed
out above, the co-ordination of these energy-exchange and
synthetic reactions presupposes the existence of a certain
organisation. It is perfectly applicable to protoplasm but not
to the primaeval solution of organic substances. In this case
it would seem far more rational to look for the immediate
sources of energy in the conditions prevailing in the sur-
rounding medium. The ideas put forward by S. E. Bresler"^
are particularly interesting in this connection. Bresler con-
siders that the free energy taken up in the formation of
peptide bonds in aqueous solution might be provided by the
work done by external compression. He therefore carried
out his syntheses under pressures of the order of some
thousands of atmospheres and, according to his reports, he
actually synthesised peptide bonds in the presence of the
appropriate enzymes, obtaining polymers of amino acids of
BIOCHEMICALLY IMPORTANT COMPOUNDS 213
high molecular weight which were, in many ways, similar
to proteins.
If this is true, the depths of the ocean, where quite a high
hydrostatic pressure prevails (though not as high as that
required by Bresler), may have been a suitable place for the
synthesis of polypeptides.
Unfortunately works have recently appeared"* which cast
doubts on Bresler's results, and we must await the experi-
mental settlement of the argument which has arisen on this
score.
In all cases where they have expressed an opinion, those
who have worked on the subject hold that it is possible that
polypeptides could have been formed in the same way in
which they are now produced in living bodies, by the poly-
merisation of pre-existing amino acids. This, however, is not
the sole or necessary way in which primary formation of
polypeptides could have taken place in the waters of the
primaeval ocean.
As a result of his extensive studies of the synthesis of amino
acids G. Ehrensvard"^ became convinced that in the syn-
thesis of polypeptides in the waters of the primaeval ocean
an extremely important part must have been played by
polymers of hydrocyanic acid, in particular the tetramer
(hcn)^ which has the structure of a nitrile
C
1
= n
1
c
1
= NH
1
c
-NH2
C = N
As early as 1911 T. B. Johnson"® demonstrated the possibil-
ity of the polymerisation of glycinonitrile in simple aqueous
solution with hydrogen sulphide
NH. CHo.CN + H,S + NH2 CH2.CN + HoS ->
NH2 CH2.CSNH2-f NH, CH2.CSNH2 ->
NH2CH2.CS.NHCH2.CS.NHCH2.es
-fNHa 4-NH, +NH3
214 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
On the basis o£ this reaction Ehrensvard considers that, in
a neutral or slightly alkaline medium in the presence of
hydrogen sulphide, (hcn)4 should be able to bring about
polymerisation, giving
NHCHR.CS.NHCHR.CS.NHCHR.es
NHCHR.CO.NHCHR.CO.NHCHR.CO
If this were confirmed we should have a very interesting
scheme for the primary formation of polypeptides.
Recently the Japanese scientist S. Akabori"^ has come
forward with extremely original and interesting ideas about
the problem with which we are concerned.
As has been pointed out above, the synthesis of amino
acids in the primaeval atmosphere must have occurred in
accordance with the following equation
R.CHO + NH3 + HCN^R.CHNHa-CN + HgO
R.CHNHo.CN + 2H,O^R.CHNH2.COOH + NH3
Akabori put forward the suggestion that polymerisation was
not undergone by the amino acids themselves but by inter-
mediate products of the reaction. For example polyglycine
might be formed not from glycine but from aminoaceto-
nitrile :
H2O
nH2NCH2.CN->( — NHCHj.C — )„ >( — NHCH,.CO - )„ + nNHg
II
NH
This gets round the difficulty of the expenditure of energy
which stands in the way of the direct synthesis of polypeptides
from amino acids. Akabori considers that particles of silicates
or clay could have catalysed the polymerisation. As the cHj
groups of the polyglycine chain become more reactive during
this process, they are adsorbed on the surfaces of solid bodies.
Immediately after the polymerisation there occurs the con-
BIOCHEMICALLY IMPORTANT COMPOUNDS 215
densation of polyglycine with various aldehydes analogous to
that which occurs with the CH2 groups of diketopiperazines :
J — CONH — CH2 — CO —
+ R— CHO
i
— CONH — CH — CO > — CONH — CH CO —
I I
HCOH CHgR
. I \ ^
— CONH C — CO —
II
CH
As well as aldehydes, unsaturated hydrocarbons can also
combine with the polyglycine chain :
— CONH — CH2 — CO — •
+ + + CH3
CH3 — CH=CH2 CH3 — CH=CH CHg \c=CH2
I i CH3/ j
— CONH — CH — CO CONH— CH — CO CONH — CH — CO —
I I I
CH CH CHg
/\ /I I
CH3 CH3 CH3 CH2 — CH3 CH
CH3 Grig
valine isoleucine leucine
Akabori confirmed his hypothesis by direct experiments
which he carried out jointly with Hakabushi and Okawa. In
the first of these experiments, in which kaolin or ai.o.j were
used at a temperature of 110° C, there occurred the poly-
merisation of CH2 : NCH2.CN or H2NCH2.CN. In this experiment
there was formed after five hours a product giving the biuret
reaction. Paper chromatography showed that it contained
glycine and polypeptides of glycine. In the second experi-
ment polyglycine adsorbed on kaolin reacted at a temperature
of 60-80° C with HCHO and CH3CH0. It was shown that this
2l6 ABIOGENIC O RG AN I C- C H E MI C AL EVOLUTION
led to the formation of polypeptides containing serine and
threonine.
The reaction of aldehydes with polyglycine adsorbed on
the surface of solid bodies gives rise to the conditions needed
for asymmetric synthesis. It is clear that if polyglycine was
adsorbed in its cis forms, so that the side-chains could only
react on the outside, the amino acid residues being synthesised
would all have the same spatial configuration, at least within
each particular polypeptide chain
H H R H R
Grl2 ClHo CHo C G C*
^ ^C — NH''^^ ^C — NH'^^ ^ > ^ ^C — NH C NH
II II II II
GO O O
This hypothesis was confirmed by experiments by Akabori
and Ikenaka on the asymmetric synthesis of phenylalanine.
According to Akabori there might thus have been formed
in the primaeval hydrosphere complicated polymers of amino
acid of high molecular weight, rather similar to proteins in
their polypeptide structure. This synthesis of protein-like
substances followed a completely different path from that
which it now follows in living organisms.
It is characteristic of living organisms that in them the
synthesis of proteins, like that of nucleic acids, is based on
a process which has already been elaborated during the slow
evolution of the organism. They arise as the product of
this organisation and their specific biologically important
peculiarities and properties are the result of this mode of
origin.
As we have seen in this chapter, the comparatively simple
laws of thermodynamics and chemical kinetics were essen-
tially what determined the course of chemical events in the
waters of the primaeval ocean. These principles provide
an understandable mechanism for the formation of sugars,
amino acids, purine and pyrimidine bases and even their
more or less complicated polymers.
Many contemporary authors believe that, on the basis of
these same laws, we shall also be able to give an explanation
BIBLIOGRAPH\ 217
of the origin of those compounds ^vhich are specific to living
things, the proteins with their enzymic activities and the
nucleoproteins with their capacity for self reproduction. Such
authors also see the primary development of these compounds
as the key to the understanding of the origin of life. These
arguments do not, however, usually amount to more than
individual general declarations and it seems to us that such
an approach to the problem which we are considering is
wrong.
The origin of proteins, enzymes, nucleoproteins and other
substances specific to living things cannot simply be based
on those laws which we have been using up till now. There
must first have arisen a new specific organisation and after-
wards, on the basis of it, the substances appeared, not vice
versa. To resolve this vexed question we must now leave, for
a while, the approach to the problem which we have hitherto
followed. Before studying the further stages in the develop-
ment of matter on the ^vay to the emergence of life we must
learn about the structure and properties of proteins, nucleic
acids and other biologically important compounds which
constitute the basis of present-day living matter.
BIBLIOGRAPHY TO CHAPTER V
1. M. DvALi and I. Andreev^ in Proiskhozhdenie yiejti (ed. by
M. F. Mirchink, A. A. Bakirov, B. F. D'yarkov and
D. V. Zhabrev), p. 83. Moscow (Gosud. nauchno-
tekhn. Izd. neftyanoi i gorno-toplivoi Lit.), 1955.
H. B. Bull. Physical BiocJiemistry. New York, 1943.
2. J. L. KuLP. Bull. geol. Soc. Amer., 62, 326 (1951)-
3. N. L. BowEN and G. F. Tuttle. Bull. geol. Soc. Amer., 60,
439 (1949)-
4. (IV. 121).
5. (IV. 12).
6. C. Koene, quoted by K. Rankama and T. G. Sahama, Geo-
chemistry. Chicago, 1950.
7. V. Vernadskii. Problemy biogeokhimii. (1st edn.) Moscow
and Leningrad (Izd. AN SSSR), 1935.
8. G. T.\MMANN. Z. phys. Chem., no, 17 (1924).
9. R. WiLDT. Rev. mod. Phys., 14, 151 (1942).
10. S. Arrhenius. Ann. Nat.- {u. Kultur)phil., p, 70 (1910).
2l8 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
11. V. M. GoLDSCHMiDT. Fortschr. Min., ly, 112 (1933)-
12. W. Groth and H. Suess. Nalurwiss., 26, 77 (1938).
13. J. H. J. Poole, as reported in Nature, Lond., 166, 761
(1950).
14. N. R. Dhar. Trans. Faraday Soc, 50, 142 (1934)-
15. G. Rathenau. Z. Phys., Sy, 32 (1933).
16. R. Mecke. Trfln5. Farada}' Soc, 27, 359 (1931).
17. A. CoEHN. Ber. dtsch. chem. Ges.,4^, 880 (1910).
A. CoEHN and G. Grote in Nernst Festschrift, p. 136. Halle,
1912.
18. A. TiAN. Ann. Phys., Paris, 5, 248 (1916).
19. H. Neuimin and A. Terenin. Acta physicochim. URSS, ^,
465 (1936)-
20. P. Harteck and J. H. D. Jensen. Z. Naturf., ^A, 591 (1948).
21. G. M. B. DoBSON. Proc. phys. Soc. Lond., 6^B, 252 (1950).
zz. H. E. Moses and Ta-You Wu. Phys. Rev., 8^, 109 (1951) ;
84, 168 (1951).
23. W. M.Latimer. Science, 112, 101 (1950).
24. V. M. GoLDSCHMiDT. Skr. norske Vidensk. Akad.
I. Mat.-naturvid. Kl. 1937, no. 4.
25. (IV. 60).
26. (III. 61).
27. J. H. J. Poole. Sci. Proc. R. Dublin Soc, 25, 201 (i950-
28. H. BoRCHERT. Geochim. Cosmochim. Acta, 2, 62 (195 0-
29. (IV. 18).
30. H. C. Urey. Proc. nat. Acad. Sci., Wash., 38, 351 (1952).
31. K. Kondrat'ev. Luchistaya energiya solntsa. Leningrad,
1954 ; Article, ' Zemlya ' (Earth). Vol. 17, Bol'shaya
Sovetskaya Entsiklopediya, 1954.
32. L. R. Roller. Ultraviolet radiation. New York, 1952.
33. A. E. H. Meyer and E. O. Seitz. Ultraviolette Strahlen.
Berlin, 1943.
34. J. A. Sanderson and E. O. Hulburt in Radiation biology
(ed. A. Hollaender). Vol. 2, p. 95. New York, 1955.
35. B. Moore. The origin and nature of life. London, 1913.
36. P. Becquerel. Astronomic, ^8, 393 (1924).
37. (in. 41). ^ , ^
38. A. Dauvillier. Astronomic, 52, 529 (1938) ; 33^ ^45 (i939)-
A. Dauvillier and E. Desguin. La genese de la vie. Paris,
1942. ,
A. Dauvillier. Genese, nature et evolution des planetes.
Paris, 1947.
39 S. Leifson. Astrophys. /., 63, 73 (1926).
BIBLIOGRAPHY 219
40. H. Thiele. Ber. dtsch. chem. Ges.,^o, 4^14. (igo8).
41. D. Berthelot and H. Gaudechon. C.R. Acad. Sci., Paris,
1^0, 1690 (1910).
42. A. Coehn and G. Sieper. Z. phys. Chem., gi, 347 (1916).
43. C. Zenghelis. CK. Acad. Sci., Paris, lyi, 167 (1920).
44. N. R. Dhar and A. Ram. /. phys. Chem., ^j, 525 (1933).
45. I. S. Stekol'nikov. Article * Molniya ' (Lightning). Vol. 28,
p. 136. Bol'shaya Sovetskaya Entsiklopediya, 1955.
46. A. I. Bachinskii. Spravochnik po fizike. Moscow, 1951.
I. S. Stekol'nikov. Molniya i zashchita ot ee deistviya.
Moscow and Leningrad (Izd. AN SSSR), 1938.
47. (in. 13).
48. (III. 46).
49. (III. 49, 50).
50. M. Berthelot. C.R. Acad. Sci., Paris, 68, 1035 (1869) ;
Ann. Chim. (Phys.), [Ser. 7], 2^, 435 (1901).
51. W. LoB. Ber. dtsch. chem. Ges., ^y, 3593 (1904) ; Z. Elektro-
chem., 12, 282 (1906) ; Biochem. Z., ^6, 121 (1912).
52. S. M. Losanitsch. Ber. dtsch. chem. Ges., 44, 312 (1911).
53. E. Briner and H. Hoefer. Helv. chim. Acta, 2^, 800 (1940).
54. V. A. Magnitskii, V. V. Belousov, E. I. Lyustikh and
S. V. KoLESNiK. Article ' Zemlya ' (Earth). Vol. 17,
p. 3. Bol'shaya Sovetskaya Entsiklopediya, 1954.
55. G. B. Boitkevich. Doklady Akad. Nauk S.S.S.R., ^4, 771
(1950).
56. R. W. VAN Bemmelen. Amer. J. Sci., 2^0, 104 (1952).
57. J. Stoklasa, J. Sebor and V. Zdobnicky. C.R. Acad. Sci.,
Paris, 1^6, 646 (1913).
58. S. C. LiND and D. C. Bardwell. /. Amer. chem. Soc, 48,
2335 (1926).
59. V. A. SoKOLOV. ijth hit. geol. Congr., Moscow, i^^'j.
Trudy, Vol. 4, p. 343. Moscow (Gos. nauch.-tekhn.
Izd. neft.-top. Lit.), 1940. For English abstract, cf.
Abstracts of papers (of above Congress). Moscow and
Leningrad, 1937.
60. W. M. Garrison, D. C. Morrison, J. G. Hamilton, A. A.
Benson and M. Calvin. Science, 114, 416 (1951)-
61. V. SoKOLOV (W. Sokoloff). Bull. Soc. Nat. Moscou (nouv-
elle serie), ^, 720 (1889-1890).
62. R. GoR\NsoN. Amer. J. Sci. (Ser. 5), 22^ 481 (1931)-
63. B. Nekrasov. Kurs obshchei khimii. Moscow (Goskhimiz-
dat), 1955.
(IV. 91).
220 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
63a. L. Khmelevskaya. Izvest. Akad. Nauk S.S.S.R. (Ser. GeoL),
I94T, no. 4, p. 107.
64. G. Stadnikov. Proiskhozhdenie uglei i iiefti. Leningrad
(Goskhimtekhizdat), 1933.
65. A. C. Gaedicke. Allgem. osterr. Chem. Tech. Ztg., 4^, 150
(1927). (Quoted by E. N. Tiratsoo. Petroleum
geology,^, z^. London, 1951.)
66. S. C. ScHUMAN. /. chem. Phys., 16, 1 175 (1948).
67. M. Karapet'yants. Khimicheskaya termodinamika. Moscow
and Leningrad (Goskhimizdat), 1953.
68. V. KoROBOv and A. Frost. Svobodnye energii organ-
ischeskikh soedinenii. Moscow (Vsesoyuzn. Khim.
Obshchestvo im. D. I. Mendeleeva), 1950.
69. V. DoLGOv. Kataliz v organicheskoi khimii. Moscow and
Leningrad (Goskhimizdat), 1949.
70. (V. 1).
71. S. Berkman^ J. C. MoRRELL and G. Egloff. Catalysis, in-
organic and organic. New York, 1940.
72. I. N. Nazarov. Uspekhi Khim., 20, 309 (1951).
73. A. E. Chichibabin. Osjiovnye nachala organicheskoi khimii.
Vol. 1. Moscow (Goskhimizdat), 1954.
74. Ya. T. Eidus. Uspekhi Khim., i^, 32 (1950).
75. A. E. Chichibabin. /. Russ. phys.-chem. Soc, (Chem.), ^y
(Otd. 1), 703 (1915)-
76. A. P. Terent'ev and L. A. Yanovskaya. Uspekhi Khim.,
23> 697 (1954)-
77. T. IsHiGURO, S. KuBOTA, O. KiMURA and S. Shimomura.
/. pharm. Soc, Japan, y^, 1009 (1954)-
78. A. BoGOMOLOv, A. GoRSKAYA and M. Messineva. (V. 1,
p. 280).
79. N. Zelinskii. Izbrannye trudy (ed. S. S. Nametkin). Vols.
I and 2. Moscow and Leningrad (Izd. AN SSSR),
1941.
80. B. T. Brooks. Industr. engng Chem., 44, 2570 (1952).
81. S. N. Obryadchikov. Neftyanoe Khoz., 24, No. 3/4, 39
(1946).
82. A. V. Frost. Neftyanoe Khoz., 24, No. 3/4, 36 (1946).
83. V. Porfir'ev. Problema nefteobrazovaniya v svete sovre-
mennykh dannykh. Moscow and Leningrad (Gostop-
tekhizdat), 1941.
BIBLIOGRAPHY 221
84. A. V. Frost. C.R. Acad. Set. U.R.S.S. 57, 223 (1942) ;
in Proiskhozhdenie nefti i prirodnykh gazov (ed. A. V.
Topchiev et al.). Moscow (Izd. NIMT Nefti), 1947 ;
Trudy Instituta goryachikh iskopaemykh Akad. Nauk
S.S.S.R., 2, 127 (1944) ; Uspekhi Khim., 14, 501 (1945).
85. A. I. BoGOMOLOv and A. I. Smirnova. Zhur. priklad. Khim.,
27. 673 (1954)-
86. N. D. Zelinskii, in Akademiku V. I. Vernadskomu k ^o-
letiyu nauchnoi i pedagogicheskol deyateVnosti (ed.
A. P. Karpinskii and A. E. Fersman), p. 875. Lenin-
grad and Moscow (Izd. AN SSSR), 1936.
87. V. SoKOLOV. Ocherki genezisa nefti. Leningrad and Moscow
(Gostoptekhizdat), 1948.
88. I. A. Breger and W. L. Whitehead. Third World Petroleum
Congress, The Hague, ip^i. Proceediyigs, Section I,
p. 421. Leiden, 1951.
A. KozLOV. Problemy geokhimii prirodnykh gazov. Moscow
and Leningrad (Gostoptekhizdat), 1950.
89. M. Karasev. Neftyanoe Khoz., i, 29 (1952).
90. V. Belousov. Ocherki geokhimii prirodnykh gazov. Mos-
cow (ONTI), 1937.
91. D. N. Andreev. Organicheskii sintez elektricheskikh raz-
ryadakh. Moscow (Izd. AN SSSR), 1953.
92. C. Ellis and A. A. Wells. The chemical action of ultra-
violet rays (revised by F. F. Heyroth). New York,
1941.
93. M. Berthelot. C.R. Acad. Sci., Paris, 82, 1357 (1876);
Ann. Chim. (Phys.), [ser. 5], 10, 69 (1877).
94. D. N. Andreev. Uspekhi Khim., 6, 1540 (1937).
95. R. V. de Saint-Aunay. Chimie et Industrie, 2g, no. 5, p.
ion (1933)-
96. S. C. LiND and G. Glockler. /. Amer. chem. Soc, y, 2811
(1929)-
S. C. LiND and G. R. Schultze. /. phys. Chem., 42, 547
(1938).
97. M. Z. JowiTSCHiTSCH. A//?. Chem., 2g, 1 (1908).
N. Ya. Dem'yanov and N. D. Pryanishnikov. /. Russ.
phys.-chem. Soc, ^8, /^Qz (1926).
98. M. Berthelot. Ann. Chim. (Phys.), [Ser. 5], 10, 51 (1877) ;
[Ser. 7], 16, 5 (1899) ; C. R. Acad. Sci., Paris, iii, 471
(1890).
S. M. LosANiTSCH. Mh. Chem., 2g, 753 (1908).
99. S. M. LosANiTSCH. Ber. dtsch. chem. Ges., ^2, 4394 (1909).
222 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
100. G. Glockler and C. A. Hollingsworth. Trans, electro-
chem. Soc, 84, 97 (1943).
101. N. Prilezhaeva and G. Neter. Zhur. fiz. Khim., 11, 254
(1938). Cf. Chem. Abstr., ^2, 7823 (1938).
102. S. M. LosANiTSCH and M. Z. Jowitschitsch. Ber. dtsch.
chem. Ges., ^o, 135 (1897).
103. A. Besson and L. Fournier. C.R. Acad. Sci., Paris, 1^0,
1238 (1910).
104. J. N. Collie. /. chem. Soc, 8y, 1540 (1905).
105. D. FiNLAYSON and J. H. G. Plant. U.S. Pat. 1, 986, 885
(1935). Through Chem. Abstr., 2p, 1021 (1935)-
R. H. Sahasrabudhey and S. M. Deshpande. /. Indian
chem. Soc, 28, 377 (1951).
106. K. Peters and H. Kuster. Brennstoff-Chem., 12, 122 (1931)-
107. M. Berthelot. Ann. Chim. (Phys.), [Ser. 4], 75, 135 (1868).
108. M. Berthelot. C.R. Acad. Set., Paris, Sj, 1141 (1868).
109. H. Becker. Wiss. Veroff. Siemens-Konzern, 8, 199 (1929).
110. G. B. Crippa and M. Gallotti. Gazz. chim. ital., ^9, 507
(1929)-
111. L. Francesconi and A. Ciurlo. Gazz. chim. ital., 55^ 327,
470,521 (1923)-
112. E. Briner and H. Hoefer. Helv. chim. Acta, 2^, 826 (1940).
113. S. M. LosANiTSCH. Ber. dtsch. chem. Ges., 41, 2683 (1908).
114. S. L. Miller. /. Amer. chem. Soc, yy, 2351 (1955)-
115. A. Pasynskii and T. Pavlovskaya. Trudy i Sytnpoziuma
po proiskhozhdeniyu zhizni, Moscow, ip^y. (In the
press.)
116. K. Bahadur. Nature, Lond., ly^, 1141 (1954).
117. K. Bakhadur (Bahadur) and S. Ranganayaki. Zhur.
obshchei Khim., 2^, 1629 (1955)-
118. W. A. Noyes and P. A. Leighton. The photochemistry of
gases. New York, 1941.
119. K. P. Bonhoeffer. Z. Elektrochem., 40, 425 (1934).
120. W. Groth and H. Laudenklos. Naturwiss., 24, 796 (1936).
W. Groth. Z. phys. Chem., B^8, 366 (1937).
121. P. A. Leighton and A. B. Steiner. /. Amer. chem. Soc,
38, 1823 (1936).
122. S. ToLLOczKO. Przemysl Chem., 11, 245 (1927).
123. R. B. Mooney and E. B. Ludlam. Trans. Faraday Soc, 2^,
442 (1929)-
124. D. Berthelot and H. Gaudechon. C.R. Acad. Sci., Paris,
755, 207 (1912).
BIBLIOGRAPHY
223
125. H. S. Taylor and D. G. Hill. /. Amer. chem. Soc, 5/,
2922 (1929)-
J. C. JuNGERs and H. S. Taylor. /. chem. Phys., 6, 325
(1938).
126. W. Kemula and S. Mrazek. Z. phys. Chem., Bi^, 358 (1933).
W. Kemula and E. M. Rauchfleisch. Roczniki Chem., 26,
221 (1952).
127. D. Berthelot and H. Gaudechon. C.R. Acad. Sci., Paris,
1^0, 1327 (1910).
128. R.Livingston. /. ^mer. c/z^m. 5oc.^ 55^ 3909 (1931).
129. G. Landsberg and A. Predwoditeleff. Z. Phys., 31, 544
(1925)-
130. H, S. Taylor and H. J. Emeleus. /. Amer. chem. Soc, 55^
562 (1931).
131. J. C. Elgin and H. S. Taylor. /. Amer. chem. Soc, $1, 2059
(1929)-
132. (V. 92).
133- (V.99. 102).
134. A. Windaus. Rapp. Cons. Chim. Solvay,6,Qi (1938).
135. M. L. Sherrill^ B. Otto and L. W, Pickett. /. Amer.
chem. Soc, ^i, 3023 (1929).
136. J. Errera and V. Henri. C.R. Acad. Sci., Paris, 180, 2049
(1925); /5 J, 548(1925).
137. R. KuHN^ F. KoHLER and L. Kohler. Hoppe-Seyl. Z., 242,
171 (1936).
138. Lord Kelvin. Quoted by E. Schroedinger. What is life}
The physical aspect of the living cell. p. 5. Cam-
bridge, 1945.
139. (in. 58).
140. V. Vil'yams. Izbrayinye sochineniya. Vol. 1. Moscow (Izd.
AN SSSR), 1950.
141. N. Kholodnyi. Izvest. Armyan. Filiala Akad. Nauk S.S.S.R.,
p-io, 89 (1942).
142. B. B. PoLYNOv. Pochvovedenie, 10, 594 (1948).
143. G. F. Gauze. Asimmetriya protoplazmy. Moscow (Izd. AN
SSSR), 1940.
144. A. Sementsov. Uspekhi Khim., 2, 225 (1933)-
145. R. D. HoTCHKiss. /. biol. Chem., 141, 171 (1941).
146. A. H. Gordon, A. J. P. Martin and R. L. M. Synge.
Biochem. ]., 57, 86 (1943).
147. M. Schoen. Prohlemes d'asymetrie dans les processus bio-
chimiques. Paris, 1936.
224 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
48. L. Pasteur. Researches on the molecular asymmetry of
natural organic compounds. Alembic Club Reprints,
No. 14. Edinburgh, 1897.
49. V. Vernadskii. Problemy biogeokhimii. (2nd edn.) Moscow
(Izd. AN SSSR), 1939.
50. A. P. Terent'ev and V. M. Potapov. Priroda, 44, No. 5,
37 (1955)-
51. L. Pasteur. Rev. sci., Paris, (ser. 3), y, 2 (1884).
52. E. Fischer. Ber. dtsch. chem. Ges., ay, 3189 (1894) ; Hoppe-
Seyl.Z., 26,60 (iSgS).
53. W. Marckwald. Ber. dtsch. chem. Ges., ^y, 349 (1904).
54. A. McKenzie. /. chem. Soc, 8^, 1249 (1904) J ^7> i373
(1905) ; 89, 365 (1906).
A. McKenzie and H. Wren. /. chem. Soc, pi, 1215 (1907).
55. G. Bredig and F. Gerstner. Biochem. Z., 2^0, 414 (1932).
56. G. Bredig and M. MiNAEFF. Biochem. Z., 2^9, 24.1 (1932).
57. For a review on asymmetric synthesis, see: A. McKenzie.
Ergebn. Enzymjorsch., ^, 49 (1936).
58. L. A. Yanovskaya. Priroda, 19^2, no. 10, p. 95.
R. CuRTi and U. Colombo. /. Amer. chem. Soc, y^, 3961
(1952)-
59. W. KuHN. Ergebn. Enzymjorsch., ^, 1 (1936).
60. F. R. Japp. Nature, Lond., $8, 452 (1898).
61. (V. 151).
62. P. Curie. /. Phys. theor. appl. (ser. 3), ^, 393 (1894).
63. J. H. van't Hoff. Die Lagerung der Atome im Raume
(Aufl. 3). Braunschweig, 1908.
64. A. Byk. Ber. dtsch. chem. Ges., ^2, 141 (1909).
65. W. KuHN and E. Braun. Naturwiss., ly, 227 (1929).
66. W. KuHN and E. Knopf. Naturwiss., 18, 183 (1930) ; Z.
phys. Chem., yB, 292 (1930).
67. S.Mitchell. J. chem. Soc, ip^o, iS2g.
68. J.C.Ghosh. J. Indian chem. Soc, 16, ^i (1939).
69. G. Karagunis and G. Drikos. Z. phys. Chem., 26B, 428
(1934)-
70. T. L. Davis and J. Ackermann. /. Amer. chem. Soc, 6y,
486 (1945)-
71. A. Byk. Z. phys. Chem., 49, 641 (1904) ; Naturwiss., i},
17 (1925)-
72. I. OsTROMissLENSKY. Bcr. dtsch. chem. Ges., 41, 3035 (1908).
73. G.-M. Schwab, F. Rost and L. Rudolph. Kolloidzschr., 68,
157 (1934)-
G.-M. Schwab and L. Rudolph. Naturwiss., 20, 363 (1932).
BIBLIOGRAPHY 225
174. A. Stankewitch. Diss., Konigsberg, 1939.
175. J. D. Bernal. Uspekhi Khim., 19, 401 (1950).
176. A. P. Terent'ev, E. I. Klabunovskii and V. V. Patrikeev.
Doklady Akad. Nauk S.S.S.R., 7^, 947 (1950) :
Uchenye Zapiski Moskov. Gosudarst. Univ., i^i, 145
(1951)-
E. I. Klabunovskii and V. V. Patrikeev. Doklady Akad.
Nauk S.S.S.R., yS, 485 (1951).
A. A. PoNOMAREv and V. V. Zelenkova. Zhur. ohshchei
Khim., 23, 1543 (1953).
177. C. Neuberg. Biokhimiya, 2, '^S^ (ig^j).
178. E. Havinga. Chem. Weekblad, ^8,642 {ic)4i).
179. E. Havinga. BiocJnm. biophys. Acta, i^, 171 (1954).
180. A. Butlerov. C.R. Acad. Sci., Paris, 55, 145 (1861) (Boutle-
row) ; Liebigs Ann., 120, 295 (1861) (Butlerow).
181. E. Fischer and J. Tafel. Ber. dtsch. chem. Ges., 22, 97
(1889).
182. O. Loew. /. prakt. Chem. (N.F.), 55, 321 (1886) ; Ber. dtsch.
chem. Ges., 22, 470 (1889).
183. E. Fischer and F. Passmore. Ber. dtsch. chem. Ges., 22,
359 (1889).
184. H. Euler and A. Euler. Ber. dtsch. chem. Ges., 59, 45
(1906.)
185. E. Fischer and K. Landsteiner. Ber. dtsch. chem. Ges.,
25^ 2549 (1892).
H. Jackson. /. chem. Soc, yy, 129 (1900).
C. Neuberg. Ber. dtsch. chem. Ges., 55, 2626 (1902).
186. E. ScHMiTZ. Ber. dtsch. chem. Ges., 46, 2^2"] (igi^).
187. L. Orthner and E. Gerisch. Biochem. Z., 2^g, 30 (1933).
188. W. W. Pigman and R. M. Goepp. Chemistry of the carbo-
hydrates. New York, 1948.
189. E. J. Lorand. f/.5. PaL 2,272,378 (1942).
190- (V. 73)-
191. J. D. Bernal. Science and Culture, ig, 228 (1953).
192. D. Shemin. Conferences et Rapports, ^eme Congres inter-
national de Biochimie, Bruxelles, 1-6 Aout 19^^. p.
197. Liege, 1956.
193. J. J. Scott. Biochem. J., 62, 6P (1956).
194. A. Treibs. Conferences et Rapports, ^eme Congres inter
national de Biochimie, Bruxelles, 1-6 Aout ig^^- p.
207. Liege, 1956.
15
226 ABIOGENIC ORGANIC-CHEMICAL EVOLUTION
195. S. W. Fox, J. E. Johnson and A. Vegotsky. Science, 124,
923 (1956)-
S. W. Fox. Amer. Scientist, 44, (no. 4), p. 347 (1956).
196. D. Davidson and O. Baudisch. /. Amer. chem. Soc, 48,
2379 (1926).
197. R. Behrend and O. Roosen. Liebigs Ann., 2^1, 235 (1889).
i98-(Vr73)-
199. H. Staudinger and K. Wagner. Makromol. Chem., 12, 168
(1954)-
200. J. C. Sonne, J. M. Buchanan and A. M. Delluva. /. hiol.
Chem., ij^, 6g (1948).
J. M. Buchanan, J. C. Sonne and A. M. Delluva. /. biol.
Chem., ly^, 81 (1948).
201. F. W. Barnes and R. Schoenheimer. /. biol. Chem., i^i,
123 (1943)-
202. D. Shemin and D. Rittenberg. /. biol. Chem., 16'], 875
(1947)-
203. J. N. Davidson. The biochemistry of the nucleic acids.
London, 1950.
204. P. Thenard and A. Thenard. C.R. Acad. Sci., Paris, ^6,
1508 (1873).
205. B. Stepanenko. Kurs organicheskoi khimii. Moscow
(Medgiz), 1955.
206. N. N. Semenov in Problemy kinetiki i kataliza. Sbornik 4.
(ed. M. Neiman). Moscow, 1940.
207. (III. 70),
208. (III. 54).
209. F. LiPMANN. Advanc. Enzymol., i, 99 (1941).
210. H. BoRSOOK. Conferences et Rapports, ^eme Congres inter-
national de Biochimie, Bruxelles, 1-6 Aout ip^^. p.
92. Liege, 1956.
211. H. M. Kalckar. Symp. Soc. exp. Biol., i, 38 (1947) ; /. biol.
Chem., 167, 4"]^ (1947).
212. M. Friedkin, H. M. Kalckar and E. Hoff-J0rgensen. /,
biol. Chem., iy8, 527 (1949).
213. R. Zahn, quoted in (III. 71).
214. G. Schmidt in Phosphorus metabolism. Symposium on the
role of phosphorus in the metabolism of plants and
animals (ed. W. D. McElroy and B. Glass). Vol. 1,
p. 443. Baltimore, Md., 1951.
F. Winder and J. M. Denneny. Nature, Lond., 174, 353
(1954)-
215. (III. 70-
BIBLIOGRAPHY 227
216. H. Staudinger and H. Schnell. Makromol. Chem., i, 44
(1947)-
217. Y. Go and H. Tani. Bull. chem. Soc. Japan, 14, 510 (1939).
218. H. M. Huffman. /. phys. Chem., ^6, 885 (1942).
219. K. Linderstrdm-Lang. Proc. Sixth International Congress
of Experimental Cytology, Stockholm, 194"]. Stock-
holm, 1949.
220. A. DoBRY, J. S. Fruton and J. M. Sturtevant. /. hiol.
C/zem., 195, 7^9(1952).
221. J. S. Fruton. 2me Congres international de Biochimie.
Chim. Biol. II. Symposium Biogenese des Proteines.
(Paris.) 1952, p. 5.
222. F. LiPMANN. Fed. Proc, 8, 597 (1949).
223. S. E. Bresler. Uspekhi sovremennoi Biol., ^o, 90 (1950) ;
Biokhimiya, 20, 463 (1955).
224. G. Talwar and M. Macheboeuf. Ann. Inst. Pasteur, 86,
169 (1954)-
225. G. Ehrensvard. Personal communication.
226. T. B. Johnson. /. hiol. Chem., g, 439 (1911)-
T. B. Johnson and G. Burnham. Amer. chem. J., ^y, 2^2
(1912).
227. (III. 73); cf. Chem. Abs., $0, 16893 (1956).
CHAPTER VI
THE STRUCTURE AND BIOLOGICAL
FUNCTIONS OF PROTEINS AND
NUCLEIC ACIDS AND THE
PROBLEM OF THEIR ORIGIN
Chemical structure and biological functions
of polypeptides and proteins.
The problem of the primary development of proteins is
extremely perplexing, not only on account of its inherent
complexity, but also because there is, at present, no agreed
definition of the term protein. Many authors of both the
nineteenth and twentieth centuries attached a purely chemi-
cal meaning to the term while others regarded it as a specifi-
cally biological concept. This is reflected in the terminology
currently used. In the Russian language the words belok
and protein are used synonymously. The Germans generally
use the term Eiweissstoff while British and American authors
have gone over entirely to the word protein, the older ^vord
' albumen ' having acquired a more specific meaning and
being applied only to a particular group of proteins of which
egg albumin is one.
In the beginning the word albumen was only applied to
the substance in hens' eggs which forms a ^vhite coagulum
when heated. Later on, other substances similar to the white
of eggs were included in the term albumen, but this concept
was not given any general biological significance in relation
to life. On the contrary, it was considered that egg albumen
and other analogous substances were no more than the specific
products of a few isolated organisms and, in particular, that
they were completely absent from plants. Thus, for example,
the gluten which had been isolated from flour as early as
the end of the eighteenth century was regarded as a curiosity,
a freak of nature, and even called matiere vegeto-animale}
How^ever, as the study of the chemical substances of living
229
230 ORIGIN OF STRUCTURES AND FUNCTIONS
nature proceeded, so the idea became stronger and stronger
in the minds of scientists that albumens are present in all
organisms and that these compounds play an extremely
important part in the process o£ life. This idea received
precise expression in the name given to albumens in the
1830s by G. J. Mulder.^ He called them protein, from the
Greek word Trpiarelos (first or most important). In using this
term Mulder was thus stressing the biological aspect of protein
as the most important component of living material. At that
time chemical knowledge of proteins was very meagre. Pro-
teins attracted the attention mainly of biologists, who usually
regarded them as the main and most important components
of the gelatinous material within the cell. This material was
called ' protoplasm ' by H. v. MohP in the middle of the
nineteenth century and the part it plays as the material
carrier of life became more and more evident. Some bio-
logists of the latter half of the nineteenth century even
identified protoplasm with protein and among them E.
Haeckel,* for example, considered that the simplest organisms
consisted of nothing but lumps of proteinaceous substances.
F. Engels,^ in common with the biologists of his time, often
used the terms ' protoplasm ' and ' albuminous bodies '
(Eiweisskorper). The ' proteins ' of Engels must therefore
not be identified with the chemically distinct substances
which we have now gradually succeeded in isolating from
living things, nor with purified protein preparations com-
posed of mixtures of pure proteins. Nevertheless Engels^ was
considerably in advance of the ideas of his time when, in
speaking of proteins, he specially stressed the chemical aspect
of the matter and emphasised the significance of proteins in
metabolism, that form of the motion of matter which is
characteristic of life.*
It is only now that we have begun to be able to appreciate
the value of the remarkable scientific perspicacity of Engels.
The advances in protein chemistry now going on have
enabled us to characterise proteins as individual chemical
* Carl Schorlemmer expressed very similar ideas (The rise and development
of organic chemistry, pp. 122-3. Manchester and London, 1879). This
topic must have been discussed by Engels and Schorlemmer during their
years of friendship in Manchester. — Translator.
POLYPEPTIDES AND PROTEINS 23I
compounds, as polymers of amino acids having extremely
specific structures. As well as this we can to a certain, though
admittedly very limited, extent relate this structure to
enzymic and other biologically important properties of pro-
teins. This will enable us to understand their extremely great
significance in the metabolic process of life. Many organic
substances of different kinds entering into the composition of
living protoplasm can only readily take part in its metabolism
after they have interacted with the proteins of the proto-
plasm to form extremely active complexes (enzyme-substrate
complexes). In the absence of such interaction the chemical
reactions of which these substances are capable take place
too slowly at ordinary temperatures for them to have any
significance in the rapidly moving process of life. Hence the
metabolic course followed by any organic compound will
depend not only on the peculiarities of its molecular struc-
ture, its chemical potentialities, but also on the specific
enzymic activity of those proteins of the protoplasm with
which the compound is involved in the general metabolism.
Thus, in proteins (enzymes) living material has both
powerful catalysts to accelerate chemical processes and an
internal chemical apparatus whereby these processes are
directed along completely determinate paths co-ordinated
with each other in a definite sequence and forming the
orderly arrangement of processes characteristic of metabol-
ism. On the basis of this organisation there also takes place,
in particular, the constant regeneration of proteins, their
self-reproduction, by virtue of which, to use Engels' words,
the protein body " while being the result of ordinary chemi-
cal processes, is distinguished from all others by being a self-
acting, permanent chemical process ".^
This presentation is, of course, radically different in prin-
ciple from those hypotheses formulated at the end of the
nineteenth century which identified protoplasm with pro-
teins and referred to the so-called ' living protein molecule '.
In these hypotheses, which were discussed more fully in
Chapter III of this book, some workers attempted to treat
protoplasm as a whole, as a single chemical substance, as a
gigantic protein molecule endowed with life (E. Pfliiger,
1875^; F. Bottazzi, 1911'; N. N. Iwanoff, 1925'°; H. G.
232 ORIGIN OF STRUCTURES AND FUNCTIONS
Doffin, 1953"). Others regarded protoplasm as no more than
a specific medium, a mixture of lifeless compounds contain-
ing the hypothetical living particles, the protein molecules,
in the chemical structure of which there lie concealed all the
causes and mysteries of life. We may refer here to the
' biogens ' of M. Verworn,^^ the ' moleculobionts ' of Alex-
ander and Bridges^'' and other similar hypothetical particles,
the chemical reality of which has never been proved by
anyone, though references to them are still to be met with in
scientific literature.
Thus contemporary chemists and biologists use the word
' protein ' in a long series of different senses. At one end
of the series we have the purely chemical definition of
proteins as highly polymerised organic compounds with very
complicated molecules made up of different sorts of amino
acids. This definition would, however, seem to be very one-
sided. It ignores the biologically important properties pos-
sessed by all the various proteins which have actually been
isolated from organisms, properties which are related to the
individual peculiarities of their structure. Such a definition
would include all polymers of amino acids, even such possible
combinations of amino acids as would not subserve the
biological functions proper to naturally occurring proteins.
Polymers of amino acids of this sort would naturally be
unable to form part of the structure of living matter. This
purely chemical definition, therefore, includes among proteins
even substances which have no direct biological significance.
On the other hand, the definition which we find at the other
end of our series, that of the living protein molecule, is
completely lacking in any clear-cut chemical meaning. The
partisans of this concept attribute to the protein molecule
(in most cases they refer to molecules of nucleoproteins) all
the properties of life, i.e. the ability to metabolise, reproduce
themselves, etc. However, they give absolutely no real
explanation of how all these properties could depend on any
particular arrangement of the atoms in the hypothetical
' living molecule '.
As a result of this confusion, many contemporary authors
studying the origin of life make quite arbitrary and illogical
jumps between the concepts of protein implied by the purely
POLYPEPTIDES AND PROTEINS 233
chemical and the purely biological definitions. For example,
they argue as follows: if the process of organic-chemical
transformation in the waters of the primaeval ocean could
have given rise to protein-like polymers of amino acids, then
the same processes must have led to the formation of ' living
protein molecules '. In what the specihc ' life-conferring '
structure of these molecules consists and how it coidd have
arisen seems to be something of an inessential detail from
this point of view ; this structure might even have been
formed as a result of purely fortuitous combinations of groups
of atoms which remained imchanged during the reproduc-
tion and multiplication of these molecules in all succeeding
generations. The perpetrators of arginnents of this sort do
not, however, notice that their approach to a solution of the
problem in hand is purely formal and verbal in character and
that what they regard as a detail constitutes the very essence
of the question.
It seems to us that the problem of the primary develop-
ment of proteins should be formulated in a different way, as
follows: the numerous and varied proteins which \ve can
now isolate from living organisms in crystalline form as
individual chemical compoinids (various enzymes, hormones,
viruses, etc.) have definite structures which are highly specific
to each of them and ^vhich are extremely well adapted to the
fulfilment of those vitally important functions which they
stibserve in living protoplasm (in metabolism, in reproduc-
tion, etc.). Substances of this kind only arise nowadays as
components of living bodies and there can be no doubt that
the specific structures w^hich they now exhibit reflect the
earlier evolution of these bodies and are the result of the
prolonged development of living organisms.^*
The main point of the qtiestion is w^hether compoimds of
this kind could arise outside living material, primarily, on
the basis of the thermodynamic and kinetic laws which \\ere
explained in the preceding chapter of this book, or whether
this required new laws of a higher order. To give a satis-
factory answer to this question it is necessary to give at least
a short account of what is now know^n of the chemical struc-
ture of the actual proteins which have been isolated from
living things and to try to understand which are the specific
234 ORIGIN OF STRUCTURES AND FUNCTIONS
features of their structure responsible for their biologically
important functions. Only after this shall we be in a position
to reconstruct for ourselves the ways by which there arose,
during the process of the development of matter, those struc-
tural peculiarities of the primaeval polymers of amino acids
which are required for the vital processes. In discussing the
chemical structure of proteins we must first make clear to
what extent these * working mechanisms ' of protoplasm
which have been isolated from living organisms (various en-
zymes, hormones, toxins, etc.) exist at the molecular level and
to what extent they appear as chemically definable substances,
in connection with which the concept of a molecule is the
same as for other organic compounds. As early as 1940 N. W.
Pirie" expressed doubts as to the validity of this approach
and to some extent these doubts still appear in the scientific
literature on proteins.^*' ^^
In fact, many proteins which were earlier thought to be
individual substances have been shown, by more refined
methods of separation, to be mixtures. For example, egg
albumin has been shown to be a mixture, notwithstanding
the fact that it forms beautiful crystals. ^^ The same is true
of serum globulins. ^^ For many years purified casein was
considered as a single protein. This seemed to be proved by
the good agreement of the analytical results obtained by
scientists in different countries. However, it has now been
established that pure casein consists of a mixture of at least
three proteins which have been separated from one another.^"
In his detailed paper dealing with the isolation of proteins
J. F. Taylor^^ points out what a complicated matter it is
to obtain individual proteins from naturally occurring mix-
tures of them. At the end of his paper he gives a list of those
proteins which are now recognised as chemically homogene-
ous compounds. We cannot be certain, however, that even
these proteins are completely uniform.
In connection with the lack of molecular homogeneity of
casein, G. R. Tristram^^ has also pointed out that ^-lacto-
globulin^' is not a single substance either, and rightly poses
the question as to whether the proteins which are now held
to be individual substances are not really mixtures of related
compounds, among which even the amino acid composition
POLYPEPTIDES AND PROTEINS 235
varies somewhat. Certainly there are a number of facts which
suggest that several pure individual protein-like substances
may form, as it were, a family of proteins, being composed
of the same amino acids but differing from one another in
the amounts of some of the amino acid residues in the peptide
chain. This may be demonstrated particularly clearly as
regards haemoglobin.^*
In this connection we must emphasise the fact that proteins
having the same biological function may differ markedly
from one another chemically. Insulin serves as a good
example of this. The hormone was isolated from the pancreas
as an individual protein of comparatively low molecular
weight, the structure of w^hich is now very well worked out.
However, it has been shown that the insulins obtained from
oxen, pigs and sheep, though they have the same physio-
logical activity, nevertheless differ from one another chemi-
cally. In particular, pig insulin contains threonine at a
position in its peptide chain where it is not present in ox
insulin. Thus it is evident that the physiological properties
of hormonal proteins do not require absolute uniformity of
structure. ^^ The same may also be said of enzymes. It now
seems quite clear that we include under the same name
(pepsin, invertase, phosphomonoesterase, etc.) proteins which
have the same enzymic activity though they sometimes differ
markedly among themselves in respect of molecular size,
isoelectric point and other physico-chemical properties and
even in respect of their amino acid compositions.^®
It follows that the catalytic properties of a given protein
are not associated with the whole of its molecule and that
this may contain parts which are completely inactive and can
easily be altered without destroying the enzymic properties.
It follows that some variations in amino acid composition do
not necessarily cause noticeable alterations in their biological
properties.
It is now well known that different forms of organisms
can contain proteins which are identical in their biological
functions but which differ in their amino acid composition.
It has also been established that changes in the living condi-
tions of organisms bring about variations in the composition
and properties of their proteins.
236 ORIGIN OF STRUCTURES AND FUNCTIONS
Having made a thorough review of the facts which we
have referred to, Tristram draws from them the following
conclusion: "That proteins do appear to remain more or
less constant in composition may well be a reflection of the
constancy of an environment, rather than evidence that
proteins are compounds of unvarying composition."
The amino acid composition and sequence in the
structure of the macromolecules of
proteins.
Having made these indispensable remarks about proteins
as individual chemical substances we can now proceed to a
proper description of the fundamentals of protein chemistry.
It may now be held to be firmly established, in the first
place, that protein molecules are made up of residues of
various amino acids and, in the second place, that these
residues are linked together in the protein molecule mainly
by peptide bonds between the a-amino groups and a-carboxyl
groups of amino acids, as was first suggested by A. Ya.
Danilevskii" and afterwards proved experimentally by E.
Fischer^* and F. Hofmeister^*' and a number of later workers.
Thus, as a first rough approximation, a protein molecule
may be described schematically as a polypeptide chain:
— CO.CH.NH.CO.CH.NH.CO.CH.NH.CO.CH.NH —
I I I I
1 2 3 4
where Rj, Ro, R3, R.,. etc., the side chains, represent the free
atomic groupings of the amino acid residues, which have very
diverse chemical properties (those of hydrocarbons, alcohols,
thiols, phenols, acids, bases, etc.).
This sort of structure fundamentally distinguishes proteins
from other organic polymers such as cellulose or rubber, in
the molecides of which the same atomic grouping (residues
of glucose, isoprene, etc.) is repeated over and over again.
Thanks to the variety of amino acid residues entering into
their composition, and also to the great chemical variety of
their functional groups, proteins have enormous chemical
potentialities. They can react with the countless multitude
of substances of living protoplasm to form either true com-
AMINO ACID COMPOSITION AND ORDER 2^7
pounds of the nature of conjugated proteins or extremely
ephemeral complexes which only have a very transient exist-
ence, as happens in the formation of intermediate compounds
(enzyme-substrate) .
Arising from this, many students of proteins from H.
Ritthausen^" to present-day authors (e.g. H. B. Vickery^^ and
W. H. Stein''^) have put forward the suggestion that the
chemical, and even the physiological, characteristics of any
particular protein could be deduced from a detailed and
complete knowledge of its amino acid composition and an
understanding of the properties of the different amino acids
of which it is made up.
Quantitative and qualitative analytical studies on various
proteins with a view^ to determining their amino acid com-
position have been going on for many years. However, the
methods devised in the classical works of A. Kossel, E. Fischer
and T. B. Osborne^^ and others depended on the separation
of amino acids from hydrolysates and involved the expendi-
ture of enormous amounts of effort, time and starting ma-
terials. For this reason such studies were very few and far
from complete. However, there have been introduced into
protein chemistry in recent years new and satisfactory micro-
methods based on up-to-date principles of investigation^'*
(isotope dilution^^ and the isotope-derivative method,^^
microbiological assay^^ and chromatography^^). This led to
signal advances in the field of amino acid analysis and a very
large number of proteins may now be taken to have been
fully analysed in this respect. (The extensive factual material
is given in the numerous tables in the article by G. R.
Tristram. ^^)
Detailed studies have also been made of the chemical
properties of the separate amino acids which are found in
proteins, those which are common to all carboxylic acids and
primary amines and also the specific functional attributes
which belong to each separate amino acid and characterise
its radical (R). The extensive data on this subject have been
recently collated in a review by P. Desnuelle.^^
The results obtained in this way were, however, rather
unexpected. In particular, it was found that only a very
limited number of different amino acids are to be found in
238
ORIGIN OF STRUCTURES AND FUNCTIONS
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AMINO ACID COMPOSITION AND ORDER 239
natural proteins, especially in those of higher animals and
plants. It is interesting to note in this connection that, as the
number of substances studied grows greater and the accuracy
of the results improves, the number of so-called ' common '
amino acids found in proteins does not increase ; in recent
years it has even shown a certain tendency to decrease. Thus
H. B. Vickery and C. L. A. Schmidt*" considered, in 1931,
that there were twenty-two common amino acids, this number
later fell to twenty-one, and now, as P. Desnuelle writes, " we
shall therefore assume twenty common amino acids only, and
this number will probably never be much modified ". We
give here a table of these amino acids and the chemical char-
acteristics of their radicals, borrowed from Desnuelle's paper
(Table 2).
The question inevitably arises as to why the endless variety
of proteins which we can isolate from contemporary animals
and plants should be made up of such a limited number of
structural elements. It is clear that as a result of the physical
and chemical laws discussed in the previous chapter there
could and must have been formed many, many other amino
acids as well as those given in the list. Why, then, do we not find
them in contemporary proteins? Obviously, in the formation
of these latter, there must have occurred a strict selection of
those amino acids indispensable for life. It would seem that
the chemical fimctions which we have just discussed are
quite sufficient for the catalysis and co-ordination of all the
various metabolic reactions. Combined with one another into
protein molecules the twenty amino acids listed form all the
enzymes necessary for metabolism and the other important
internal chemical mechanisms of living protoplasm. There
can be no doubt that in the process of evolution of living
matter there took place a rationalisation of these mechanisms
and consequently a standardisation of them, analogous to
that occurring in technical processes. All those amino acids
which were not absolutely necessary to life were eliminated
in later generations by natural selection.
R. L. M. Synge^^ has written very pointedly:
If we assume, on the basis of evolutionary theory, that the
proteins of highly organised beings became progressively more
240 ORIGIN OF STRUCTURES AND FUNCTIONS
and more efficient in carrying out their particular functions,
then it is reasonable to suppose that their component parts (as
it were the nuts and bolts of the mechanism) have been to a
great extent standardised, just as in modern engineering the
component parts have been standardised so that they can be
used to make all kinds of things from sewing machines to motor-
car engines.
The idea of the standardisation of the amino acid composi-
tion of proteins during the process of evolution of higher
organisms finds support in the fact that among organisms
at a lower stage in evolutionary development — mainly bac-
teria and fungi — we find, in addition to the ordinary amino
acids which are constantly present in proteins, that there are
continually being discovered new, so-called ' peculiar ' or
' uncommon ' amino acids such as /3-thiolvaline in Penicil-
lium spp.,^^ mf50-ae-diaminopimelic acid**" and other amino
acids. *^ There are also found in the proteins and peptides,
and particularly in the antibiotics, of lower organisms the
' unstandardised ' D-forms of amino acids, among them d-
glutamic acid in the capsule of Bacillus anthracis*'^ and
related organisms, D-leucine in gramicidin,*^ D-phenylalanine
in gramicidin S*® and tyrocidine*^ {B. brevis), D-alanine in
Lactobacillus arabinosus,^^ etc. In higher organisms, on the
other hand, we invariably find only L-forms of amino acids
and apparent exceptions to this rule have always been found
to be artefacts arising by racemisation, usually during the
hydrolysis of the proteins.*^
Thus we see that during the course of evolution the transi-
tion from the lower forms, with their as yet imperfectly
organised metabolism, to higher forms in which the metabol-
ism has reached a higher degree of co-ordination, is marked
by a standardisation of the amino acid composition of pro-
teins due to natural selection. Thus, one of the essential
properties of the animal and vegetable proteins which we
have studied, their amino acid composition, is not entirely
determined by physical and chemical laws alone but carries
the imprint of its biological origin.
Another deduction which can be drawn from a thorough
study of the amino acid composition of present-day proteins
does not bear out the optimistic expectations, referred to
AMINO ACID COMPOSITION AND ORDER 24I
above, of many chemists of the past and present centuries
beginning with Ritthausen and ending with Vickery. It has
been shown that even the most complete amino acid analysis
of a particular protein taken by itself is still far from char-
acterising the physical and chemical properties of that pro-
tein, let alone its biological functions. As K. Bailey^" wrote
recently :
One of the most disheartening features of the amino-acid
analysis of proteins is that the results have little meaning. To
a limited extent they are useful for assessing the nutritional
value of a protein, but they do not explain at all the true bio-
logical function ; why one protein is an enzyme, another a
hormone, another a toxin.
This is quite understandable even on purely theoretical
grounds. Never in the history of science could it be main-
tained that the whole is nothing but the sum of its com-
ponent parts. (" The whole is always somewhat different
from the sum of the separate parts," M. Planck, 1935.) In
proteins it is the structure which determines this difference.
Even a study of the chemical properties of artificially syn-
thesised polypeptides shows that the chemical activities of
free amino acid groups (the so-called radicals, R) are markedly
changed when they are included in peptide chains, and also
depend on the order in which they are arranged in the
chains.^*
Even by simply comparing the effects of various substances
and physical factors on a mixture of amino acids and a poly-
peptide composed of those same amino acids, it will be found
that the amino acid residues of peptides are considerably
more labile. For example, they are far easier to racemise
than the corresponding free amino acids. In just the same
way, the chemical reactivity of particular functional groups
such as the hydroxyl group of serine, the phenolic hydroxyl
gi'oup of tyrosine, the co-amino group of lysine, etc., is very
substantially altered according to which chemical groups are
immediately adjacent to them in the polypeptide chain. In
a number of cases amino acid radicals, when forming part
of a polypeptide chain, can react with compounds to which
16
242 ORIGIN OF STRUCTURES AND FUNCTIONS
they would be quite indifferent in the form of free amino
acids. G. R. Tristram^- sums the matter up as follows:
It is now appreciated that the properties of side chains in a
protein are not simple functions of the properties of the free
amino acids, but are, in fact, highly complex functions dependent
on many factors including the relative distribution of side chains
in the main peptide chain and in the folded native protein.
The order in which the amino acid residues are arranged
in the peptide chains of native proteins or biologically impor-
tant peptides isolated from organisms has long attracted the
attention of scientists. The elucidation of this problem has,
however, been attended by a very large number of technical
difficulties.*
The first reasonably successful attempt to establish the
order in which all the amino acid residues are arranged in a
single protein-like substance was made by K. Felix and his
colleagues^ ^ on the protamine of herring sperm, clupeine.
They considered that the molecule of clupeine is made up of
no more than 33 amino acid residues, namely, 22 of arginine,
2 of alanine, 2 of serine, 3 of proline, 3 of valine and 1 of
hydroxyproline. The unusually small number of amino acid
residues and absence of any great diversity, in particular the
extreme predominance of arginine, greatly simplified the task
of studying this peculiar protein. In Felix' opinion the amino
acids in the polypeptide chain of clupeine are arranged in a
rather regular way ; there are always a series of four arginine
radicals in a row along the chain followed by two residues
of other amino acids and then again four arginine residues,
etc.
M. Bergmann^^ put forward the hypothesis that the
polypeptide chains of other proteins besides clupeine are
constructed similarly and that they also contain a definite
repetitive sequence of amino acid residues. For example, if
there are 54 lysine residues in edestin out of a total of 432,
this means that every eighth amino acid residue in the poly-
peptide chain of edestin will be lysine. Similarly, in ox
globin, each of the 36 lysine residues will be separated from
* The earlier efforts in this direction have been reviewed by R. L. M.
Synge, Chein. Rev., 52, 135 (1943). — Translator.
PHYSIOLOGICALLY ACTIVE COMPOUNDS 243
the next by 15 residues of other amino acids and each of the
12 residues of proline will be separated from the next by 47
other residues, etc."
Hormones, enzymes, antibiotics and
antigens.
However, this hypothesis that the structure is fundament-
ally related to the ratios between the numbers of different
amino acid residues in any particular protein was not con-
firmed by the direct study of the breakdown products ob-
tained by partial hydrolysis of proteins and polypeptides.
On the contrary, the application of this tedious but very
reliable method has actually enabled people to elucidate the
very complicated arrangement of the amino acid residues in
the peptide chains of a number of physiologically important
compounds. This applied, in the first place, to toxic sub-
stances produced by bacteria (antibiotics), such as gramicidin.
By partial hydrolysis of the simplest of these, gramicidin S,^*
which is a cyclopolypeptide," it has been possible to isolate
numerous dipeptides and tripeptides by paper chromato-
graphy. By comparing these, the whole sequence of amino
acids in this cyclic peptide has been established.^^ Further-
more, the use of similar methods has led to the elucidation
of the sequence of the amino acid residues in tyrocidines
A and B^^ and other polypeptide antibiotics.'^^
Corresponding studies on proteins are naturally of special
interest. The one which has now been most thoroughly
studied is insulin. This hormone, which is particularly
important on account of its physiological activity, has been
studied by many workers, both in respect of its amino acid
composition and in respect of the arrangement of the amino
acid residues in the polypeptide chain. ^^
The work of F. Sanger and his colleagues'^'' has given a
clear picture of this structure. Sanger marked the terminal
amino groups of the polypeptides present in insulin by
condensing them with 2 : 4-dinitro-i-fluorobenzene ; he then
submitted this derivative of insulin to partial hydrolysis and
studied the breakdown products obtained in this way. On
the basis of the results thus obtained Sanger then arrived at
244 ORIGIN OF STRUCTURES AND FUNCTIONS
the structure of insulin as follows: the molecular weight of
soluble insulin is about 48,000. It varies, however, with the
concentration and pH of the solution. When the pH is less
than 4 or more than 7-5 the insulin molecule dissociates into
parts with a molecular weight of 12,000. These parts are each
composed of four open polypeptide chains in two of which
(the A chains) the terminal amino group belongs to a glycine
residue and the terminal carboxyl group to an aspartic acid
residue. The corresponding terminal residues in the other
two chains (the B chains) are phenylalanine with a free amino
group and alanine with a free carboxyl group.
NH, I S S 1 NH, NHj NH;
II I II
Gly lieu Val.Glu.Glu Cy.Cy.AIa Ser . Val . Cy . Sor . Leu Tyr Glu Lou Glu. Asp.Tvr.Cv Asp
I ■ r
s s
NH.NH. S S '
III I
Phe Val.Anp.Glu.His.Lcu.Cy.Cly .Ser. His . Leu. Val . Glu . Ala. Leu Tyr Leu . Val .Cy Gly Glu. Arg Gly Phe.Phe.Tyr Thr Pro Lys Ala
Fig. 15. Formula of ox insulin.
Sanger and colleagues" consider that, strictly speaking, the
basic unit of insulin is a particle with a molecular weight of
6,000 consisting of one A chain and one B chain joined
together by disulphide bridges. Their complete formula for
ox insulin is shown in Fig. 15. According to C. Tanford
and J. Epstein,*^ two such particles are joined together by
means of zinc atoms to form a particle with a molecular
weight of 12,000.
These data as to the sequences of amino acid residues in
the polypeptide chains of insulin do not show the periodicity
in the arrangement of amino acids suggested by Bergmann.
The arrangement here is far more complicated. Two identi-
cal amino acid radicals may be side by side or may be
separated from one another by any number of other residues.
There is no obvious regularity or rhythm in these sequences.
Moreover, a definite sequence must be present, at least in
some part of the molecule, if the protein is to exercise its
physiological functions. We still do not know why this is so,
we cannot explain the immediate cause of this specificity,
but facts which have been obtained recently demonstrate
beyond doubt that the specificity exists both for insulin and
for other analogous hormones. For example, the two hor-
PHYSIOLOGICALLY ACTIVE COMPOUNDS 245
mones of the posterior lobe of the pituitary (oxytocin and
vasopressin) are very similar in their amino acid composi-
tion," but even the small differences in the details of their
structure confer on each its own essential hormonal function
which it alone can carry out.
In oxytocin the sequence is Cys. Tyr. lieu. Glu. Asp. Cys.
Pro. Leu. Gly. In vasopressin the sequence is Cys. Tyr. Phe.
Glu. Asp. Cys. Pro. Arg. Gly.
Interesting results have been obtained by P. H. Bell and
R. G. Shepherd®* concerning the structure of the ^-adreno-
corticotrophic hormone (ACTH). This is a polypeptide with
a molecular weight of 5360 and the following arrangement
of amino acid residues: Ser. Tyr. Ser. Met. Glu. His. Phe.
Arg. Try. Gly. Lys. Pro. Val. Gly. Lys. Lys. Arg. Arg. Pro,
Val. Lys. Val. Tyr. Pro. Asp. Gly. Ala. Glu. Asp. Glu. Leu,
Ala. Glu. Ala. Phe. Pro. Leu. Glu. Phe.
It is important that the biological activity of the hormone
only depends on the presence in the correct order of the
amino acids 1 - 24 starting from serine. The rest of the chain
is of no importance for its hormonal activity.
Unfortunately we have not yet got the same information
concerning the sequences of amino acids in enzymes that we
have in hormones. In this case, however, the connection
between these sequences and the specific catalytic action of
the enzyme in question seems clearer. If the enzyme is to
hasten the transformation of the substance which acts as its
substrate it must first combine with that substance.
For enzymes with two components w^hich have specific non-
protein (prosthetic) groups as well as proteins in their mole-
cules, it has long been established that the combination of
the enzyme with the substrate takes place through the pros-
thetic gi'oups.®^
For example, W. Langenbeck" showed in his model
experiments that the ability of carboxylase to catalyse the
decarboxylation of pyruvic acid is associated with the pres-
ence of an amino group in the molecule of the enzyme.
Simpler compounds containing this group, such as methyl-
amine, can also accelerate this reaction. The catalytic activity
of methylamine is, however, very slight, but can be made
many times greater by incorporating, in the molecule of
246 ORIGIN OF STRUCTURES AND FUNCTIONS
methylamine, carboxyl, phenyl and other groups which do
not in themselves have carboxylase activity but considerably
augment this activity of the amino group.
It has further been shown*^ that natural carboxylases, that of
yeast, for example, have as a prosthetic group a phosphorylated
derivative of vitamin Bj. In this compound the amino group
is combined with the heterocyclic pyrimidine and thiazole
rings, which confer on it a very high catalytic activity. Not
only that, but when the thiamine pyrophosphate is combined
with a specific protein the complex acquires a catalytic activ-
ity as a decarboxylase** nearly 10,000 times greater than that
of the most efficient of Langenbeck's artificial models.
A similar situation is found when we study other enzymes
having two components, in particular the oxidising enzymes
cytochrome oxidase, *^^ peroxidase,''" etc.
Catalase,'^^ which catalyses the breakdown of hydrogen
peroxide to oxygen and water, is also a compound of a specific
protein with a prosthetic group, haem." The combination
of this enzyme with its substrate is brought about through
the agency of the iron in the haem. Even ions of inorganic
iron have a weak catalytic activity. If, however, the iron is
combined with a pyrrole nucleus its catalytic activity is
increased several fold. Haem, in which the iron is combined
specifically with four pyrrole nuclei, has a specific catalytic
activity about 1,000 times greater than that of inorganic iron.
In the natural enzyme the haem is combined with a specific
protein. As a result of this, its activity is increased ten million
times more. One milligramme of iron combined in the cata-
lase complex manifests a catalytic activity which it would
require ten tons of inorganic iron to produce.
Thus the presence of a particular group in the prosthetic
part of an enzyme with two components seems to be a pre-
requisite for its activity, because without it the enzyme
cannot combine with its substrate. The essential strength
and specificity of enzymic catalysis is, nevertheless, associated
with the protein component of the enzyme.
We often find the same prosthetic group in a number of
different enzymes. Nevertheless, there is a fundamental
qualitative difference between them, both as regards the
substrates on which they act and the nature of their reactions
J tV -4 K ^ ■
Fig. i6. Crystals of pepsin
(after Northrop, Kunitz and Herriott).
PHYSIOLOGICALLY ACTIVE COMPOUNDS 247
with these substrates. This is due to the fact that the same
prosthetic group is combined with proteins which have
different compositions and structures. For example, there
exist no less than 15 different enzymes which have as
their prosthetic group phosphopyridoxal (vitamin Bg). But,
depending on the protein component, one will catalyse the
transamination of amino acids, others their decarboxylation,
still others the formation of indole from tryptophan, hydro-
gen sulphide from cysteine, etc.^^
As well as the enzymes with t\vo components ^ve no^v kno^v
a large number of enzymes which can be prepared in crystal-
line form and which, on hydrolysis, break doAvn completely
to amino acids. They therefore cannot contain prosthetic
groups and would appear to be simple proteins.''^ Enzymes
of this kind, having only one component, cannot enter into
combination with their substrates otherwise than by means
of the free functional groups of the amino acid residues com-
prising their polypeptide chains (Fig. 16).
Unfortunately, present-day protein chemists only know the
complete amino acid composition of a very limited number
of crystalline enzymic preparations. We give the facts for
four proteins of comparatively low molecular ^veight which
have enzymic actions, and for five with higher molecular
weight (Table 3).
A knowledge of these figures for the amino acid composi-
tion is, however, of very little help in determining the causes
of the activity of any particular enzyme. On the contrary,
many contemporary authors emphasise the fact that proteins
having similar amino acid compositions may have very dis-
similar enzymic activities while, on the other hand, two
preparations of the same enzyme isolated from different
sources are often very different in amino acid composition.'^^
This should not surprise us. As we have shown above,
only a certain number of the amino acid residues in its
polypeptide chain play a part in determining the specific
biological activity of /S-ACTH. w^hile others are relatively
unimportant in this respect. There are a number of facts
which suggest that among enzymes, too. their activities are
associated with particular parts of the molecule. Centres of
activity may be found in them, groups of amino acid radicals
248
ORIGIN OF STRUCTURES AND FUNCTIONS
Table 3. Amino Acid Content of Some
Amino
acid
Chymo-
trypsinogen
(ox pancreas)
(mol. wt.
25,000)
Ribonuclease
(ox pancreas)
(mol. wt.
15,000)
Pepsin
(ox stomach)
(mol. wt.
34.500)
Lysozyme
(hen's egg)
(mol. wt.
14.700)
No
I
II
III
I
II
III
I
II III
I II
III
I
Alanine
7-6
7-4
21
—
—
—
—
— —
60 5-1
10
2
Arginine
2-8
5-6
4
52
102
5
10
2-2 2
129 225
11
3
Aspartic acid
11-3
7-3
21
14-2
9-1
16
160
11-5 41
182 103
20
4
Glutamic acid
90
5-3
15
130
7-5
13
11-9
7-7 28
4-3 2-2
4
5
Cysteine
1-3
09
3
06
0-4
07
0-5
04 2
0 0
0
6
Cystine/ 2
3-3
2-4
7
6-5
4-6
8
1-6
1-3 4
80 5-0
10
7
Glycine
5-3
61
18
1-3
1-5
3
6-4
8-2 29
5-7 5-7
11
8
Histidine
1-2
20
2
4-2
6-9
4
0-9
1-7 2
10 1-5
1
9
Isoleucine
5-7
3.8
11
31
20
4
108
7-9 28
5-3 30
6
10
Leucine
104
6-9
20
0
0
0
104
7-6 27
8-4 4-8
9
11
Lysine
80
9-5
14
10-4
121
11
0-9
1-2 2
5-9 61
6
12
Methionine
1-2
0-7
2
4.4
2-5
5
1-7
11 4
20 l-O
2
13
Phenylalanine
3.6
1-9
5
3.6
1-8
3
6-4
3-7 13
31 1-4
3
14
Proline
5-9
4-4
13
3.6
2-7
5
50
41 15
1-4 09
2
15
Serine
11-4
9-4
27
120
9-7
17
J 0. Q
111 40
7.0 50
10
16
Threonine
11-4
8-3
24
90
6-4
11
9.6
7-7 28
5-4 3-4
7
17
Tryptophan
5-6
4-7
7
0
0
0
2-4
2-2 4
106 7-8
8
18
Tyrosine
30
1-4
4
7-9
3-7
7
8-5
4-5 16
3-7 1-5
3
19
Valine
101
7-4
22
7-3
5-3
9
7-1
5-8 21
4-7 2-2
6
20
Amide (nh^)
Total I
1-86
9-5
(27)
2-5
12-5
(22)
1-6
9-0 (32)
1-8 8-0
(18)
ip-p6 io.f-p :
140 ioS-8
98-9
121 114-9
98-7 306 115-4 97-4 .
^29
I, g. amino acid/ 100 g. protein ; II, g. N/100 g. total N ;
PHYSIOLOGICALLY ACTIVE COMPOUNDS
249
Crystalline Enzymes (after Desnuelle, VI. 75)
No.
Triose-
phosphate
Aldolase dehydrogenase
(rabbit muscle) (rabbit muscle)
(mol. tut. (mol. wt. Phosphorylase
140,000) 99,000) (rabbit muscle)
Lipoxi-
dase
(soya)
(mol.ivt.
102,000)
Pyro-
phosphatase
(yeast)
(mol. zvt.
100,000)
I
II III I
II III I
II IV I III I
II III
1
s
3
4
5
6
7
8
9
10
II
12
13
14
15
16
17
18
19
20
8-6 8-0 135 6-7
6-3 12-1 51 5-2
97 61 102 124
11-4 6-5 109 6-8
[ 11 08 13 11
6-4 75 4-8 4-5 54
10-2 30 11-6 22-6 67
80 93 9-3 5-9 70
3-9 46 13-4 7-8 91
— — 64 6-2 72
4-7 30 3-2 7-3 18
6-2 47 142 93 107
104 73 10-2 6-8 69
0-8
04 04
5-6
6-2
105
60
6-9
80
3.8
4-3
51
6-3
82
3
7
4-3
49
4-2
6-8
38
50
8.3
32
3-3
5-4
21
3-6
22
2
6
4-3
17
7-9
50
84
91
5-9
69
6-5
4-2
50
8-1
63
10
3
6-8
79
"•5
7-3
123
6-8
4.4
51
10-5
6-8
80
11-4
89
7
5
4-9
57
9-5
109
91
9-4
110
64
7-2
8-4
49
7.8
54
12
5
148
85
1-2
06
11
2-7
1-7
18
2-7
1-5
18
1-6
13
1
6
06
11
31
1-5
26
55
2-9
33
6-2
3-2
38
4-9
30
7
I
3-7
43
5-7
4-1
69
3-7
2-7
32
4-7
3-5
41
51
46
7
4
5-5
64
7-3
5-8
97
8-5
69
81
3-1
2-4
30
—
—
3
7
3»
35
7-4
4-8
87
7-6
5-5
63
4-2
30
35
8.9
53
5
9
4-3
49
2-3
1-9
16
20
1-7
10
20
1-6
10
0-4
4
3
6
3i
18
5-3
2-4
41
4-6
2*2
25
5-9
2-8
33
6-2
35
6
5
3-1
36
7-4
5-3
88
120
90
105
7-3
5-3
62
7-8
65
5
0
3-7
43
11
5-4
(91)
1-2
5-8
(67)
1-5
7-3
88
—
—
1
4
7-4
(82)
II6-6
roi-^ 1286 ii6-j
104-2
51/(5
108-4
100-9
803
93-4
706
7/2
8
99-2
852
III, no. of residues/molecule ; IV, no. of residues/ 10^ g.
250 ORIGIN OF STRUCTURES AND FUNCTIONS
which also appear to combine directly with the molecules of
the substrate, like the prosthetic groups in enzymes which
have two components/'^
In a number of cases it is quite evident that the groups in
question are very small in comparison with the size of the
whole molecule of the enzyme. The molecular weight of the
enzyme urease, for example, is almost 10,000 times that of
its substrate, urea, and it must have a reactive centre which
is, relatively, extremely small. By inhibiting urease with
silver ions it has been shown that each molecule of urease
must contain three or four such centres. ^^
We can form an opinion as to the chemical nature of the
amino acid radicals at these centres by blocking them with
some substance which has a specific activity." By this means
it has become clear that it is not just one particular radical
which is responsible for the activity of the enzyme, but
several amino acids arranged close together in the protein
molecule. For example, the catalytic activity of lysozyme
depends on the presence of the following free (unblocked)
groups: amino, amido, carboxyl, guanidine, hydroxyl and
disulphide groups.^"
R. M. Herriott^^ gives some interesting facts about the
chemical structure of chymotrypsin and pepsin. Comparative
study by blocking the free functional groups in active
enzymes and their inactive precursors enables one to estab-
lish the relationship between the catalytic activity of a given
protein and the presence of one or another amino acid
radical. For example, it has been shown that di-?5opropyl
fluorophosphate combines with chymotrypsin but not with
its precursor. When this happens, the hydroxyl group of
serine is blocked. In the precursor this hydroxyl group forms
part of an ester linkage and is only liberated from this by
hydrolysis. Besides the hydroxyl group of serine, the imidazole
ring of histidine is also necessary for the activity of chymo-
trypsin. In just the same w^ay the proteolytic activity of
pepsin depends on the presence of the free carboxyl and
phenolic groups of tyrosine.
I. B. Wilson^^ has to some extent succeeded in elucidating
the structure of the active centres of cholinesterase. One
should not, hoAvever, suppose that it is only the groups within
PHYSIOLOGICALLY ACTIV^E COMPOUNDS 25I
the active centres of the enzyme which are important for its
catalytic activities. As with the prosthetic gioups of enzymes
with two components, they are required only for the initial
step, the first stage of the enzymic activity, that is to say, for
the combination of the enzyme with its substrate. Thus, if
the active centre is absent or blocked no catalytic activity
of any sort can occur. However, if the reaction is to be accom-
plished, the mere combination of the enzyme with the sub-
strate is not enough. A further transformation is necessary,
as a result of which the appropriate changes take place in the
substrate and the enzyme is regenerated in its original form.
If this does not happen, not only is the enzyme unable to
accelerate the reaction, but it is itself bound up, immobilised
in a stable compound.
It is still not clear which are the details of the structure
of the protein molecule associated with these final stages of
the catalytic activity of the enzyme. Contemporary scientific
literature on this subject consists only of various more or less
probable hypotheses (cf. H. Neurath and G. W. Schwert,^^
P. V. Afanas'ev,^* S. E. Bresler^^ and others). There can,
however, be no doubt that the protein molecule as such takes
part in the catalytic process, not merely as the active centres
which enter into direct combination with the substrate.
It is interesting to compare this suggestion with the results
obtained by M. Znamenskaya, P. Agatov and A. N. Belozer-
skii*® in their work on the mechanism of the biological
activity of gramicidin S. These workers showed that the
amino group is very important indeed in connection with
the activity of this antibiotic. This group should, however,
only be regarded as the active centre uniting the antibiotic
with the substrate. The nature and specificity of the activity
of gramicidin S depends on the structural features of the
molecule as a whole.
Enough has been said to show that the order in which the
amino acid residues are arranged is of the first importance
in determining the specific biological functioning of enzymes.
This order, to some extent, includes both the structure of
the active centre and those details of the construction of
the protein molecule which are important for its catalytic
activity.
252 ORIGIN OF STRUCTURES AND FUNCTIONS
Unfortunately we have, at present, only a very limited
amount of information on this subject and what we have is
concerned mainly with enzymes of low molecular weight.
In particular, C. Fromageot and his colleagues^^ and later
K. Ohno'* have established the sequence of the amino acids
in some separate fragments of lysozyme (molecular weight
14,700). A. Thompson*^ obtained from lysozyme a series of
penta-, tetra-, tri- and dipeptides and worked out the order
in which the amino acids are arranged in them. This order
has not, however, been established for lysozyme as a whole.
Similar studies with ribonuclease (molecular weight 15,000)
are on the way to giving a complete picture of the sequence
of amino acids in it.^°
On the basis of what we know we can already put forward
the hypothesis that the sequence of the amino acid residues
in the polypeptide chains of various enzymes is not less com-
plicated than that in insulin and other similar hormones
and also that, like the biological activity of the hormones,
that of the enzymes is determined, in the first place, by this
specific structure of the polypeptide chains.
It must not be forgotten that in the protein molecule these
chains are disposed in a definite three-dimensional arrange-
ment, the structure of which is of extreme importance in
determining the biological characteristics of the protein in
question. The chemical potentialities of the side chains and
of the polar terminal groups of the amino acid residues are
not only realised in external reactions but also in forming
internal linkages. This leads to an orderly twisting of the
peptide chain and its unification into an extremely well-knit
three-dimensional structure with an ordered internal con-
figuration.
A structure of this sort is very characteristic of the protein
molecule. Other filamentous molecules, such as rubber, can
also curl up into lumps as a result of the thermal motion of
their different parts. However, the structure of these lumps
seems to be fortuitous. The separate parts are not connected
together in any orderly way and the lump may easily be
uncurled merely by the application of mechanical tension.
The internal structure of the protein molecules, on the
other hand, seems to be perfectly orderly. In them the separ-
PHYSIOLOGICALLY ACTIVE COMPOUNDS 253
ate parts of the peptide chains and closed rings seem to bear
a definite spatial relationship to one another, which is recipro-
cally strengthened by the drawing together of these parts by
means of covalent and ionic bonds, as well as by less stable
bonds such as hydrogen bonds. ^^
This sort of structure confers a definite size and shape on
the fundamental molecular unit of the protein. These units
may combine with one another to give discrete particles of
uniform size having a relatively low degree of association,
which are usually referred to as molecules of ' globular ' or,
more accurately, corpuscular proteins, although it would
have been more proper to have given them the name of
micelles or molecular complexes.®^ In many cases they may
be easily and reversibly dissociated into the fundamental
units, which demonstrates the fact that the bonds uniting the
fundamental units with one another in their polymers are
weaker than those within the fundamental units themselves.
It may easily be understood that the three-dimensional archi-
tecture of the molecule is of decisive significance in determin-
ing the chemical potentialities of a given protein, and thus
also its biological properties. Proteins having an identical
structure of their peptide chains but with different spatial
arrangements of them must obviously also have different
enzymic, hormonal or immunological properties.
This is due to the fact that when the chains curl up and
form lateral linkages, separate parts of them are necessarily
brought into close approximation with one another. As a result
of this, amino acid radicals which are widely separated along
the peptide chain and even radicals belonging to different
chains may be brought together in the protein molecule into
the same reactive centre of an enzyme or into the three-
dimensional ' chemical relief ' of the surface of the molecule,
which forms the basis for the combination of the antibody
with the antigen in immunological reactions.®^
This type of configuration also means that, while some of
the active groups of the amino acid residues find themselves
on the surface of the protein molecules and therefore avail-
able for chemical activity, others are hidden in the depths of
the molecule, protected or ' screened ' by the groups which
happen to be near them, so that the chemical and even the
254 ORIGIN OF STRUCTURES AND FUNCTIONS
biologically important properties of the protein may change
while the composition of its peptide chains and their sequence
remain the same.
The correctness of this general picture is confirmed by
an immense amount of factual material derived from the
fields of both enzymology and immunochemistry.^* Experi-
ments on the denaturation of biologically active proteins are
specially convincing in this respect. This phenomenon is
induced by the action of very diverse physical and chemical
factors such as heating, vibration, the action of urea or ultra-
violet radiations, etc. It is not accompanied by dissolution
or rearrangement of the covalent bonds of the peptide chains
of the protein.''^ The specific three-dimensional architecture
of the protein molecule is, however, severely disturbed.^®
The first more or less satisfactory theory of denaturation was
put forward by H. Wu."^ According to this theory, denatura-
tion occurs as a result of the disruption by the denaturing
agent of the weak bonds which subsist between the peptide
chains. When this takes place, they arrange themselves in a
random and disorderly way corresponding with the most
stable thermodynamic state.
According to A. E. Mirsky and L. Pauling^^ the configura-
tion of the native protein molecule is maintained by hydrogen
and salt bonds, which unite the different parts of the peptide
chains. When denaturation occurs, these bonds are broken,
the chains fall apart and many radicals which were previously
hidden within the molecule become available for chemical
reactions.
This explains the change in the reactivity of proteins on
denaturation.^" In particular, it was shown some time ago
that the number of sulphydryl and disulphide bonds avail-
able for reactions was greater in denatured proteins than in
the same proteins in their native state."" Denatured proteins
also give stronger reactions for tyrosine"^ and arginine"^ and
will combine with larger amounts of iodine."^
According to contemporary ideas the structure of native
proteins consists of closely packed, coiled or twisted peptide
chains which untwist on denaturation to give extended
chains without any significant rearrangement which would
involve disruption of their covalent bonds.""*
PHYSIOLOGICALLY ACTIVE COMPOUNDS 255
A very characteristic feature of denaturation is the dis-
appearance of the biological properties of the native protein.
On denaturation the physiological activities of hormones are
destroyed, enzymes lose their catalytic powers and the sero-
logical specificity of proteins disappears. The inactivation of
enzymes, in particular, seems to be one of the commonest
phenomena in laboratory practice and examples in the
scientific literature of thermostability among enzymes (e.g.
ribonuclease or lysozyme) or of their regeneration after
denaturation seem to be the exception rather than the rule.^"'
The same may be said of serological specificity. For in-
stance, it is widely known that denatured egg albumin, like
other proteins, does not react nearly so well with the antibody
which is formed by the native protein."^ J. O. Erickson and
H. Neurath, however, believe that serological activity is asso-
ciated with structures which are the last to be affected by
denaturation."^
From all that has been said it follows that the biological
specificity of proteins and, in particular, the catalytic activity
of enzymes is related not only to a particular sequence of
amino acid residues in the polypeptide chains but also to
the way in which these chains are arranged inside the mole-
cule of any given protein. Owing to its extreme significance,
the structure of the protein molecule has long engaged the
attention of scientists. Many of them have tried to construct
a schematic representation of this structure on purely theore-
tical foundations. For example, D. M. Wrinch"* once did so,
mainly on the basis of geometrical considerations.
A very interesting hypothesis concerning the structure of
the molecules of globular proteins has been formulated by
D. L. Talmud and S. E. Bresler."^ These authors assumed
that, as the result of the definite and regular sequence of
amino acid radicals, the non-polar (non-ionising) groups such
as the hydrocarbon radicals of alanine, leucine, ?5oleucine,
valine, phenylalanine, etc., were mainly arranged on one
side of the peptide chain, while the polar (ionising) groups
such as the radicals of aspartic and glutamic acids, serine,
arginine, lysine and histidine were arranged on the other.
This may be represented for the ideal case by the following
diagram (Fig. 17).
256 ORIGIN OF STRUCTURES AND FUNCTIONS
A chain constructed in this way would be subject to the
action of two opposing forces, the attractive force between
the non-polar, predominantly hydrocarbon, side chains, and
the repulsive force between the ionising amino acid radicals
O
O Q
o
Fig. 17. Diagram of the structure of the polypeptide
chain (after Talmud and Bresler).
O — polar (ionising) groups
non-polar (non-ionising) groups.
Fig. 18. Diagram of the coiling of the
polypeptide chain.
(having similar charges at the given pH of the surrounding
aqueous medium). Owing to this, the chain would twist into
a spiral in the middle (nucleus) of which would be the hydro-
carbon (hydrophobic) groups while on the outside, which
faced the aqueous medium, would be the ionising groups
(Fig. 18).
PHYSIOLOGICALLY ACTIVE COMPOUNDS
2r.
0/
If this were to happen, additional Knkages would arise
between adjacent turns of the spiral, in particular hydrogen
bonds between the — nh — and -co — groups. The elucida-
tion of the actual arrangement of the amino acid residues
in the polypeptide chains of such a typical globular protein
as insulin seems to be does not, however, confirm this idea.
In this case there is an irregular sequence of polar and
non-polar residues (Fig. 19) so that the chain will not be
twisted up to form a globule in the way Talmud and Bresler
imagined.""
O Q
O
O
O
0 006
Fig. 19. Polypeptide chain B of the molecule of insulin.
Direct investigation of the structure of corpuscular pro-
teins by the diffraction of X-rays"^ and infra-red rays"^ shows
that this structure is, in fact, far more complicated than any
of the schemes drawn up on the basis of general physico-
chemical considerations.
In her review B. W. Low"^ points out that of the whole
number of proteins which have been studied in this respect
" at best a ' bird's-eye ', long distance view of some protein
molecules has been derived. It is, however, far from a
detailed or precise description of the molecular architec-
ture. . . ."
Nevertheless, it may now be held to be established that
the essential molecule of corpuscular proteins does not consist
of globules but of bundles of polypeptide chains."^ A struc-
ture of this sort may be made up either of chains which
are, in fact, separate (as has been shown in the case of insulin)
or of parts of a single polypeptide chain pleated like a ribbon
folded back and forth on itself.
In a molecule of native corpuscular protein these chains
are twisted or folded in a definite way or curled into helices.
It is very likely that in some, though not in all, corpuscular
17
258 ORIGIN OF STRUCTURES AND FUNCTIONS
proteins there is a structure of the type of the a-helix of
L. PauHng, R. B. Corey and H. R. Branson,"^ a diagram
of which is here reproduced (Fig. 20).
A helix of this sort is obtained when the chain is twisted
in such a way that each
group is united with the
third group away from it
by means of a hydrogen
bond. A complete turn
of the helix contains 3-7
amino acid residues. The
helix advances 5-44 A
for every turn ; each
amino acid residue there-
fore occupies 1-47 A
measured parallel to the
axis of the helix. This
helix is far more stable in
LINKAGESJ jj-g energy relations than
other suggested configura-
26 A
5^6 H BONDS
(18 PEPTIDE
Fig. 20.
System of hydrogen bonds in
the helical configuration of
the polypeptide chain having
3-7 residues per turn (after
Pauling, Corey and Branson).
tions of peptide chains and corresponds most nearly to all
the theoretical and experimental data.
Nevertheless, B. W. Low"^ writes:
The problem of protein structure is not simply, however, the
problem of polypeptide chain configurations. In all the native
protein structures examined in detail there appear to be several
chains or lengths of chain arranged in parallel close packed
array. The stability of the molecule as a whole must depend,
therefore, upon the nature of the interchain bonding. In the
helical structures the side-chain groups are thrown outwards
BIOSYNTHESIS OF PROTEINS 259
towards the perimeter of the coil, and interchain stability must
depend, therefore, on side-chain interactions. The reactivity of
the molecule is further dependent both upon the sequence of
the amino acid residues along a single length of chain and upon
the relationships between the residues in adjacent chains.
All these, ^vith other related factors, together determine
the complicated three-dimensional surface relief of the mole-
cule of any particular protein which is responsible for its
hormonal, enzymic, immunological or other biologically
important properties.
The biosynthesis of proteins.
It no^v remains for us to answer the question as to whether
such an extremely complicated and specific structure as the
molecule of a present-day protein with its definite amino
acid composition, its particular arrangement of amino acid
residues in a polypeptide chain and, finally, its precise
internal architecture, so thoroughly and well adapted to the
performance of definite biological functions, -^vhether this
structure cotild arise spontaneously, simply in the primaeval
aqueous solution of the hydrosphere. Many contemporary
authors answer this question in the affirmative, taking the
view that there first arose enzymes in this solution of organic
substances. These were self-reproducing proteins like viruses,
etc., and later combined together, giving rise to the primaeval
organisms. It is not, however, so easy to substantiate this
sort of general statement."®
In the first place, how can one explain the origin of the
complicated sequences of amino acids w^hich are found in
insulin and other similar proteins? D. L. Talmud and S. E.
Bresler once suggested a hypothesis according to which the
polypeptide chain was an assemblage of different amino acids,
the proportions and sequence of ^shich Avere statistically
determined by their concentrations, but this hypothesis seems
to be an oversimplification. The free energies of the poly-
peptide bonds between the different amino acid residues
in a protein are not identical. There is also a correlation
between the heat effects of reactions and the energy of their
activation. Thus, according to A. G. Pasynskii,"' the incor-
poration of different amino acids into polypeptide chains
260 ORIGIN OF STRUCTURES AND FUNCTIONS
must proceed at different rates and this must also affect their
arrangement. The speed of the reaction whereby amino acid
residues are incorporated does not, however, depend entirely
on their inherent chemical properties but, in living organ-
isms, it is mainly determined by the presence of a collection
of enzymes. It follows that the extremely uneven but strictly
determined sequences of amino acid residues in the poly-
peptide chains, which are to be found in any proteins which
have been isolated from living bodies, arise as a result of
a pre-existing organisation of their protoplasm. This applies
even more forcibly to the three-dimensional structure of
corpuscular proteins, which clearly requires for its develop-
ment a certain spatial organisation. In the absence of such
an organisation which had already been elaborated, there
could clearly never have arisen simply in an aqueous solution
of organic substances such structures as those of present-day
proteins with their peculiar properties.
This is also evident because the particles of present-day
proteins are not only extremely complicated in structure but
are also extremely well adapted to carrying out particular
biologically important functions. Enzymes, hormones, etc.,
seem to be perfectly rationally constructed organs of living
protoplasm. Therefore the hypothesis that they arose primar-
ily in some way, and that protoplasm itself was later gradually
built up from them, reminds one of the hypothesis of the
ancient Greek philosopher Empedocles, concerning the origin
of living things.
Empedocles believed that at first there arose separate,
independent organs: "Out of it (Earth) many foreheads
without necks sprang forth, and arms wandered unattached,
bereft of shoulders, and eyes strayed about alone, needing
brows.""* Later on these disunited members joined them-
selves together and in this way there arose various animals
and people.
From the present-day Darwinian point of view the falsity
and absurdity of hypotheses of this sort are obvious. Any
particular organ can arise and become perfected only by the
evolutionary development of the organism as a single whole.
The definite, complicated structures of eyes and hands are
only adapted to the purpose of fulfilling those functions
BIOSYNTHESIS OF PROTEINS 26l
^vhich these organs carry out in the ^vhole organism. The
effect of natural selection is, therefore, only exerted on them
as parts of the whole living thing. It is impossible, unthink-
able, to imagine the evolution of isolated organs, the " eyes
needing bro^vs " of Empedocles, because for them alone the
function to which their structure is adapted has no meaning.
The same applies to the catalytic powers of enzymes. For
example, the po^ver of carboxylase to decarboxylate pyruvic
acid is of no significance for the enzyme itself, but is only
significant for the organism in which the reaction in question
occurs. This reaction is only one link in a long chain of
energy-yielding transformations of sugar, and if the rate at
which it proceeds is co-ordinated with the rates of other
metabolic reactions, this will give an advantage to the par-
ticular living body in the process of natural selection. It is
therefore hard to agree with the recent suggestions of M.
Calvin"' about the possibility of the primary origin of
enzymes by the gradual natural selection, from among a
tremendous number of randomly changing organic mole-
cules, of particles with structures which were more and more
successfully adapted to the carrying out of particular catalytic
fimctions.
For example, Calvin considers that in the primaeval
solution of organic substances there occurred a selection
of molecules with a continually increasing amount of car-
boxylase activity, like that brought about by Langenbeck by
artificial selection of his carboxylase models: methylamine,
glycine, phenylaminoacetic acid, aminooxindole, etc.
According to Calvin, the natural selection of molecules
having a gradually increasing carboxylase activity in the
primaeval hydrosphere took place because this activity was
associated with autocatalysis and accordingly the more effici-
ently the molecule of a catalyst could decompose pyruvic
acid, the faster the catalyst itself would be formed.
The models which have so far been constructed by Langen-
beck do not, hoAvever, bear this out. Their carboxylase
activity increases, btit no autocatalysis can be observed. The
artificial models have no such property nor, it would seem,
has the coenzyme of carboxylase, vitamin Bj, nor carboxylase
itself. One would expect that, if the primary origin of
262 ORIGIN OF STRUCTURES AND FUNCTIONS
enzymes was based on selection for autocatalysis, the proteins
of the present time would have that property to the same
extent as they have their specific catalytic effects. But this
is not so. An example of the formation of enzymes by simple
autocatalysis, which caused a great sensation at one time in
the scientific literature, is the formation of trypsin from
trypsinogen.^^" In this case there certainly did seem to occur
an autocatalytic increase in the number of molecules of the
enzyme. If a small amount of trypsin is added to a solution
of trypsinogen (which is not proteolytic and may be con-
sidered as the nutrient medium in this case) additional
amounts of the active enzyme are rapidly formed. One test
tube of trypsinogen which has been ' inoculated ' with trypsin
may be used for the inoculation of fresh ' media ' and the
process may be repeated again and again (as is done in the
subculturing of bacteria) with the formation of ever more of
the enzyme.
However, a more careful study of the mechanism whereby
this phenomenon is produced shows that, in this case, we
are not, in fact, dealing with the synthesis of trypsin de novo.
The enzyme is present in trypsinogen in its entirety, but its
activity is blocked by a peptide which is combined with it
(just as the ignition key of a car is rendered useless for start-
ing the engine when it is immobilised in the lock of the
door). The proteolytic activity of trypsin depends on the
activation of trypsinogen simply by the removal of the key
from the lock and has nothing to do with the autocatalytic
synthesis of fresh enzyme molecules. ^^^
The same may be said of the formation of pepsin by
analogous means, from pepsinogen. ^^^ As regards other
enzymes, in particular enzymes such as carboxylase or cata-
lase, they do not even give a semblance of forming themselves
autocatalytically. Like the other proteins of protoplasm, they
can only come into being there as a result of a very compli-
cated biosynthetic process.
At present biochemists are only beginning to collect the
facts in the field of protein synthesis. The scientific literature
concerned with this subject, therefore, contains very few
firmly established theories but many more or less plaus-
ible hypotheses of various sorts and extremely ingenious
BIOSYNTHESIS OF PROTEINS 263
mathematical speculations, which attempt to reduce this
complicated biological phenomenon to comparatively simple
mathematical terms, just as Wrinch tried to postulate a struc-
ture for the globular protein on the basis of purely geo-
metrical considerations. However, we can already say with
certainty that nowhere in nature can we observe the forma-
tion of proteins by the direct ' birth ' of one molecule from
another identical one, as was imagined even quite recently.
The chemically individual proteins which have been isolated
do not arise of themselves by the ' division ' of molecules nor
by simple automatic autocatalysis. We can, in fact, only
olDserve the production of proteins in living bodies, and this
process requires the harmonious participation of a series of
systems including many different protein-enzymes.
We can nowadays point to at least three categories of such
systems, the co-operation of which is indispensable for the
biosynthesis of proteins: i, systems which supply the energy
needed for the synthesis of the protein ; 2, catalytic (enzymic)
systems which create the kinetic conditions for the synthesis,
a definite relationship between the rates of the different
reactions ; 3, systems which determine the spatial organisa-
tion during the synthesis of the protein molecule.
The method of synthesis of proteins from amino acids
seems to be common to the majority of present-day organisms,
though one cannot exclude the possibility that some pre-
formed peptides may be incorporated in the chains.^" As
was pointed out in the previous chapter, this method of
synthesis requires a certain expenditure of energ)% which
must be supplied to any system in which proteins are formed
directly.
In all heterotrophic organisms the basic source of the
energy required for life seems to be the energy derived from
the anaerobic or aerobic breakdown of organic substances,
mainly carbohydrates (fermentation, glycolysis, respiration).
The autotrophs also make extensive use of this method,
decomposing and oxidising the carbohydrates which they
have made by photo- or chemosynthesis. The various fer-
mentations, glycolysis and respiration, seem to be carried
through by very highly co-ordinated enzymic reactions. Their
realisation requires the presence of a very complicated system
264 ORIGIN OF STRUCTURES AND FUNCTIONS
of enzymes in which, as will be shown later, the more com-
plete the organisation of any particular system the higher its
energetic efficiency and the greater the extent to which the
energy produced by it can be used for the carrying out of
vital processes, in particular for the formation of the proteins
of protoplasm. In the course of these metabolic processes
there arise many kinds of high-energy compounds and the
energy which they yield can be used, in one way or another,
for biological syntheses. The best known of these compounds
is adenosine triphosphoric acid (ATP), which can hand over
the energy of its phosphate linkages by the transphosphoryla-
tion of a number of organic compounds.
F. Lipmann''* and other authors (e.g.'") have suggested
that the increment of energy required for synthesis of peptide
bonds when amino acids combine may be obtained by the
phosphorylation of their amino or carboxyl groups at the
expense of ATP or some analogous substance. This sugges-
tion is confirmed by various sorts of model experiments in
which hippuric acid is synthesised from glycine and benzoic
acid,'^^ and also by the synthesis of the tripeptide, gluta-
thione, from its component amino acids in slices and
homogenates of various organs'" as well as in experiments
with yeast. '^* S. Yanari and his colleagues'-^ have shown
recently that an enzyme which they isolated from pigeon's
liver can bring about the synthesis of glutathione from its
amino acids only when the system contains ATP and glyco-
lytic processes are proceeding.
Lipmann's hypothesis concerning the biosynthesis of pro-
teins is, to some extent, confirmed by the fact that anything
which interferes with phosphorus metabolism hinders this
synthesis. Thus, in the experiments of E. F. Gale and J. P.
Folkes,'^° fragments of staphylococcal cells were able to in-
corporate isotopically-labelled amino acids and synthesise
proteins from complete collections of amino acids only on
the addition of ATP and hexose diphosphate as sources of
energy. Analogous phenomena were observed by F. B.
Straub'^' during the synthesis of amylase by homogenates
of the pancreas.
On the other hand, it must be pointed out that nobody
has yet succeeded in directly observing the phosphoryla-
BIOSYNTHESIS OF PROTEINS
265
tion of amino acids, while synthetic phosphorylated amino
acids which are artificially introduced into an organism do
not enter directly into the synthesis of proteins. It must
therefore be admitted that the actual mechanism of the
transfer of energy during the synthesis of proteins is still not
quite clear. H. Borsook"^ considers that there first occurs
the activation of the carboxyl groups of free amino acids by
ATP, either directly or through coenzyme A. Afterwards
the activated amino acids combine with nucleic acid accord-
ing to the following scheme :
base
base
base
base
sugar sugar [e — co — chRi — NHg
/I / 1 /
o o o o + i +
1/1/
0=P 0=P ^E — CO — CHRg — NH2'
OH
OH
sugar
/ I
o o
I /
o=p
I
o
sugar
I /
o o
1/
0=P + 2EH
I
O
0=G — CHNH2 0=C — CHNH2
/ /
Ri
Peptide bonds are then created, after which the finished
protein molecule is liberated from the nucleic acid.
On the other hand, according to S. E. Bresler,^^^ energy
is necessary for the last stage of the process, the desorption
of the polypeptide chain from the surface of the polynucleo-
tide. According to this author, the biosynthesis of proteins is
based on the chemosorption of amino acids on the energy-
bearing phosphorylated gioups of ribonucleic acid. Under
the conditions of the adsorbed layer the equilibrium is
shifted towards synthesis. The action of proteolytic enzymes
will therefore lead to the joining together of amino acids
and the synthesis of protein molecules, which does not
require the additional expenditure of energy. Energy is
required for desorption of the finished protein molecule and
this is derived from high-energy bonds in the phosphorylated
nucleic acid. The surface which has been freed from the
protein is again phosphorylated and the cycle repeats itself.
266 ORIGIN OF STRUCTURES AND FUNCTIONS
The very interesting experimental results obtained by
R. B. Khesin^^^ show that isolated secretory granules of the
pancreas cannot make direct use of the energy of ATP for
the synthesis of the protein-enzyme amylase. In them the
synthesis of the enzyme from free amino acids only occurs
as a result of the activity of substances which are elaborated
independently by other formed elements in the protoplasm,
the mitochondria, in the course of their energy-exchange
reactions which take place in the presence of ATP under
aerobic conditions. The actual synthesis of protein by the
granules can, however, proceed in the absence of oxygen.
The part played by enzymes in the processes supplying the
energy required for synthesis is now ^vorked out in great
detail but the position is far worse in regard to the part
played by enzymic systems directly in the biosynthesis of
proteins.
As early as 1886 A. Danilevskii"^ first indicated that syn-
thetic reactions might be brought about with the help of
proteolytic enzymes. On digesting dilute solutions of different
proteins with pepsin and then concentrating the peptones
thus obtained and allowing fresh portions of pepsin to act on
them, Danilevskii observed the formation of an insoluble
precipitate, which he believed to be protein ^vhich had
arisen as a result of the enzymic synthesis. Furthermore, it
was established that these precipitates, which were called
' plasteins ', could be obtained from peptic hydrolysates of
a very large number of proteins by enzymic synthesis because,
owing to the removal of the insokible products of the reaction
by precipitation, the equilibrium was displaced away from
hydrolysis and towards the synthesis of peptide bonds. ^^® The
plasteins have since been studied in detail by all modern
methods."^ They seem to be polypeptides, with molecular
weights of some thousands, containing a predominance of
hydrophobic amino acids and apparently lacking any specific
biological properties."*
Comparatively recently H. Tauber"' has succeeded in
bringing about the enzymic synthesis of proteins by the
action of chymotrypsin on a mixture of peptides. Chymo-
trypsin also catalyses the formation of peptides from esters
of amino acids, in which reaction the energy needed for the
BIOSYNTHESIS OF PROTEINS 267
synthesis is supplied by the simukaneous decomposition of
the esters/*" M. Bergmann^*^ also brought about the syn-
thesis of peptides. He obtained anilides of acylamino acids
from the corresponding amino acid derivatives and various
anilides by the action of papain and chymotrypsin on them.
In recent years a number of authors have been laying more
and more stress on the part played by transamidation^'^ and
transpeptidation^*^ in the process of the biosynthesis of pro-
teins. The enzymic nature of these processes is indubitable
and the only question which is not yet quite clear is whether
there are specific enzymes for transpeptidation or whether
the proteolytic enzymes themselves perform this function.^**
In particular, I. L. Kaganova and V. N. Orekhovich"^ have
observed a large number of transpeptidations occurring under
the influence of chymotrypsin.
It must, however, be admitted that, notwithstanding all
this, the direct participation of the enzymic apparatus of
the protoplasm in the biosynthesis of proteins has still not
received nearly enough study. In particular there remains
the vexed question of the part played by enzymes in the
creation of the specific structure and properties of the
proteins which have been synthesised.
As early as 1939, M. Bergmann put forward the opinion
that the sequence in which the amino acids are arranged
in the polypeptide chain is determined by the relative rates
of the different enzymic reactions co-operating in the syn-
thesis.
This opinion is not ^videly supported in the world litera-
ture at present chiefly because people are distracted by the
part played by spatial factors in the determination of the
specificity of proteins. For example, F. Haurowitz^^ states,
during the development of his hypothesis concerning the
synthesis of proteins on an extensive ' protein template ','"
that the amino acids Avhich are arranged in a particular order
on this template combine together owing to the action of
non-specific proteolytic enzymes such as trypsin or papain.
He adds that the specificity of the synthetic processes may
now be attributed, not to the specificity of the catalysts, but
to the specificity of the organiser or inductor.
A. L. Bounce used to believe that, for amino acids to
268 ORIGIN OF STRUCTURES AND FUNCTIONS
combine with definite parts of the polynucleotide chain
during the process of the synthesis of proteins, the participa-
tion of a large number (up to 64) of specific enzymes was
required. He is now inclined to deny the necessity for such
far-reaching enzymic specificity. ^^'^
Unfortunately there is, as yet, very little direct factual
evidence on this problem upon which to base a definite con-
clusion. One should not forget, however, that in all cases
where the biosynthesis of any substance has been studied in
enough detail, it has been shown to be based on a chain of
strictly co-ordinated enzymic reactions. Moreover, the simple
consideration of the magnitude of the free energy of the
peptide bonds between different amino acid residues and
the energy of activation needed for the formation of these
bonds shows that the incorporation of different amino acid
residues in polypeptide chains must take place at different
rates. Thus the kinetic conditions, which are fundamentally
regulated by enzymes, must play an essential part in the
synthesis of proteins.
Thus, while giving due weight to the importance, for
the synthesis of proteins, of spatial factors in the organisation
of protoplasm, one must not forget about its organisation in
time, the conjunctions of kinetic circumstances which deter-
mine a particular type of metabolism. In this connection
a very important place is occupied by the catalytic (enzymic)
systems.
The significance of spatial localisation in all vital processes
and, in particular, in biosynthesis was recognised by the
biologist R. Altmann"* as long ago as 1886. In his book
Studien iiber die Zelle he very perspicaciously put forward
the idea that the synthetic processes do not occur diffusely
throughout the protoplasm but are associated with definite
structures in it, which he called ' granules '. This idea of the
localisation of the synthetic processes in formed elements of
the protoplasm was maintained by G. Lewitsky^*^ who worked
on plant preparations, by A. Guilliermond^^" on the basis
of his observations on mitochondria, and later by E. W.
MacBride and H. R. Hewer,^^^ E. S. Horning^" and many
other authors.
Since then more and more facts have been collected which
BIOSYNTHESIS OF PROTEINS 269
indicate that the bulk of the enzymes are associated with the
formed elements of the cell contents, which gives a special
character to the activity of these biocatalysts which is sub-
stantially different from that observed in simple aqueous
solutions of enzymes isolated from cells. It was thus estab-
lished that even slight changes in the composition of proto-
plasmic structures occurring under the influence of external
factors have a substantial effect on the speed and nature of
synthetic reactions within the living cell.^"
Damage to or disruption of these structures, which occurs
under even the mildest conditions, leads to the complete
abolition of biosynthesis. For example, the bacterium Micro-
coccus lysodeikticus may be treated with lysozyme without
disturbing the structures in the least, if the lysis is carried
out in the presence of sucrose. ^^* When this takes place, the
protoplasts retain their ability to incorporate marked mole-
cules of glycine and leucine in their protein.^" However, it
has been shown in our laboratory that if the concentration of
sucrose is gradually lowered, a definite point is reached when
the concentration falls below 0-64 m and the structure of
the protoplasts is disrupted. This can easily be checked with
the electron microscope. At the same time there is a sharp
fall in the respiration of the protoplast, and later, when the
concentration of sucrose falls below 0-44 m, the protoplast
loses its ability to incorporate marked glycine and to syn-
thesise protein in the presence of a complete collection of
amino acids. ^^® Obviously there is a limit to the amount of
damage which the structure of the protoplast can suffer,
beyond which the biosynthesis of protein becomes impossible
owing to the loss of that co-ordination of the reactions in
time which only occurs when the enzymes are placed in
special positions relative to one another in the protoplasm
(Fig. 21).
In recent years a large number of papers have appeared
showing how particular enzymes are associated with this or
that demonstrable structure, whether it be plastids,^^^ mito-
chondria or microsomes, ^^* and hence which biochemical
processes are localised in these formed elements of the
protoplasm. Thus it has been established that there are
concentrated in the mitochondria the enzymes taking part
270 ORIGIN OF STRUCTURES AND FUNCTIONS
in the Krebs cycle, cytochrome oxidase and also other oxidis-
ing enzymes such as succinic, lactic and glycerophosphate
dehydrogenases.^^
I K
mOr HO
159
mo
woo
^
^
§
^ 800
dOO
I 400
ZOO
J.
X
J.
Fig.
OM 0J4 0,64 0,54 0,44 Q34 024
SUCROSE M
21. The respiration of the protoplasts of
Micrococcus lysodeikticus and the uptake of
labelled glycine.
The enzymes in the mitochondria are not arranged at
random but stand in a definite spatial relationship to one
another, which is associated with a very precise internal
structure of the mitochondria. This reduces the path which
must be followed by the substrate or coenzyme to a minimum,
which allows a considerable speeding up of long chains of
reactions such as the citric acid cycle. K. Lang^^" showed
that anything which destroys the structure of the mito-
chondria inactivates the so-called cyclophorase system of
enzymes discovered in the mitochondria by D. E. Green and
his colleagues.^"
BIOSYNTHESIS OF PROTEINS 271
The essential energy-exchange processes of the cell are
associated with the enzymes which have been found in the
mitochondria. It is clear that the main biological function
of the mitochondria consists in the formation of energy-rich
compounds.
Rather unexpectedly, it was found that the bulk of the
enzymes associated with the metabolism of the nucleic acids
(ribonucleic acid, RNA, and desoxyribonucleic acid, DNA)
was localised in the mitochondria."^ This led to the idea
that nucleic acid synthesis might be localised in the mito-
chondria. However, direct experiments did not verify this
suggestion."^ In the same way all contemporary investi-
gators agree that the actual synthesis of proteins does not
occur in the mitochondria.
At one time T. Caspersson"^ suggested that the nucleus
is the main centre for the synthesis of proteins, but direct
studies of biosynthesis in fragments of algae (Acetabularia)
containing no nuclei, carried out by J. Hammerling"' and
later by J. Brachet and H. Chantrenne,"® disproved this
hypothesis. On the contrary, the numerous results obtained
by J. Brachet and R. Jeener,"^ T. Hultin,"^ E. B. Keller,"'
P. Siekevitz and P. C. Zamecnik^'^" have shown quite definitely
that the proteins of the cytoplasm are synthesised directly
in the microsomes. The nucleus only takes part indirectly in
the synthesis of proteins, perhaps by controlling the forma-
tion of the microsomes themselves.
According to Siekevitz, ^'^^ however, the incorporation of
amino acids into the proteins of the microsomes is only
observed ^vhen microsomes and mitochondria are incubated
together. Under these circumstances the reaction proceeds
much faster when the conditions are suitable for oxidative
phosphorylation. The mitochondria may also be incubated
without the microsomes in a solution containing an oxidis-
able substrate and co-factors. In this case the mitochondria
form a high-energy factor, Avhich enters the solution, and in
the presence of this the isolated, incubated microsomes retain
their ability to incorporate labelled alanine.
Thus we have here Tvhat might be called a division of
labour between the two sorts of protoplasmic structures. One
system of enzymes is localised in the mitochondria in which,
272 ORIGIN OF STRUCTURES AND FUNCTIONS
SO to speak, they are ' assembled ' into a single structural
aggregate which works up the energy-rich compounds
required for the synthesis of proteins. The synthesis itself is,
however, carried out in another structural aggregate, the
microsome or, as Brachet^" calls it, with reference to its high
content of ribonucleoproteins, a * ribonucleoprotein granule '.
A comparison of the evidence concerning the synthesis of
peptide bonds in the protoplasmic structures of animal and
vegetable cells has revealed some differences in these pro-
cesses. Thus, according to N. Sisakyan,^^^"" the incorporation
of labelled glycine takes place considerably faster in those
fractions of a homogenate of tobacco leaves which contain
mitochondria than in those which contain plastids. Never-
theless it is only in the plastids that one can observe an
increase in the amount of protein nitrogen derived from
mixtures of amino acids.
The idea that RNA plays an important part in the syn-
thesis of proteins arose quite a long while ago on the basis
of biological observations and quantitative experiments which
showed a close correlation between the rate of synthesis of
proteins and the amount of nucleic acids in organs, tissues
and the organelles of cells. In growing and secreting organs,
i.e. those in which proteins are being synthesised fastest,
the amount of ribonucleic acid is found to be greatest. On
the other hand the parts of adult organisms which only grow
slowly or have stopped growing altogether only contain a
relatively small amount of RNA even in cases where the
organ is biologically extremely active and carries out a great
deal of work in the organism (e.g. the heart or kidneys).^"
In parallel with this, cytological studies have sho^vn that
the synthesis of proteins proceeds with special intensity in
just those parts of the cell which are richest in RNA. In
particular, in the nucleus the synthesis of proteins is con-
centrated only in the heterochromatic nucleoli while in the
cytoplasm it is concentrated in the mitochondria, which are
exceptionally rich in ribonucleic acid.^''*
The association between the intensity of protein formation
and the concentration of ribonucleic acid has been confirmed,
not only by cytochemical means but also by the use of more
accurate methods,^" in particular by the use of labelled
BIOSYNTHESIS OF PROTEINS 273
atoms. ^'"^ In this way it has been possible to find a correlation
between the rate of synthesis of proteins and the rate of
renewal of phosphorus in RNA, the activity of phosphatase,
etc.
Direct evidence of the dependence of protein synthesis
on the presence of nucleic acids was obtained by E. F. Gale
and J. P. Folkes"" in their work on the incorporation of
amino acids into proteins bv fragments of staphylococci
which were obtained by disintegrating the organisms by
ultrasonic vibrations. Nucleic acids can be removed from
these fragments by washing. When this is done they lose
their ability to incorporate amino acids and synthesise pro-
tein. This ability is, however, restored by the addition of
RNA and DNA isolated from staphylococci to the medium
in which the fragments are incubated.
It is very interesting that the ability of disintegrated
staphylococcal cells to incorporate separate amino acids into
proteins is affected not only by native RNA but also by its
breakdown products obtained by splitting it with ribo-
nuclease. When this was done there were isolated from among
the products several fractions which could bring about the
incorporation of amino acids but the incorporation of each
different amino acid was accelerated by a particular fraction.
Thus, the incorporation of amino acids into the proteins of
the cell fi'agments does not require RNA as an intact mole-
cular complex but the presence of small fragments of the
molecule is enough. Gale therefore considers that the in-
corporation of each amino acid may be regarded as a separate
and independent reaction associated '^vith a special poly-
nucleotide fragment. Recently, however, there has arisen
some doubt as to whether this action is due to the individual
polynucleotide fragments or to some other active compounds
contained in the fraction.
The study of viruses is of special importance for an under-
standing of the part played by nucleic acids in protein syn-
thesis, and especially the study of the simplest viruses patho-
genic to plants. The most thoroughly studied of these is
tobacco mosaic virus, which was discovered by D. Ivanovskii^^^
as early as the end of the nineteenth century. The study
of tobacco mosaic virus has made great strides forward since
18
274 ORIGIN OF STRUCTURES AND FUNCTIONS
the end of 1935 when W. M. Stanley^'' succeeded in isolating
it in crystalline form. This virus, as well as a whole series of
analogous viruses producing diseases in higher plants, has
been studied by Stanley himself and also by F. C. Bawden,
N. W. Pirie, R. Wyckoff, J. D. Bernal, R. Markham, H.
Fraenkel-Conrat, G. Schramm and, in the Soviet Union, by
V. Ryzhkov, K. Sukhov, P. Agatov, A. Vovk, M. Gol'din
and many others. There has also been extensive progress in
the study of the bacterial viruses or bacteriophages, and
especially of the viruses of animals and man which are of
medical importance. The scientific literature on viruses has
grown to an immense size. We shall only refer here to a
limited number of review works which contain extensive
references to the literature. ^^^
The great advantage of studying tobacco mosaic virus, as
an approach to the solution of a number of general biological
questions, lies in the relative simplicity of its composition.
While the particles of other viruses such as the animal viruses
of the smallpox-psittacosis group contains lipids, carbo-
hydrates and other substances as well as nucleoproteins, the
crystals of tobacco mosaic virus are composed entirely of
nucleoproteins. But, unlike other nucleoproteins which
have been isolated from living things, the virus has the
specific property that when it is introduced into the living
cell of the plant it evokes in the host a turbulent process of
biosynthesis of the particular proteins and nucleic acids
which are characteristic of the virus but which are absent
from the healthy tobacco leaf. In this way the amount of
virus in the cells of a large plant may increase many million-
fold within a few days. However, nobody has succeeded in
producing this so-called ' multiplication ' of virus particles
under any other conditions or on any artificial medium.
Outside the host organism the virus remains just as inert in
this respect as any other nucleoprotein. Not only does it
show no sign of metabolism but nobody has yet succeeded
in establishing that it has even a simple enzymic effect. It
is clear that the biosynthesis of virus nucleoproteins, like
that of other proteins, is brought about by a complex of
energic, catalytic and structural systems of the living cell
of the host plant, and that the virus only alters the course of
BIOSYNTHESIS OF PROTEINS 275
the process in some way so as to give specific properties to
the final product of the synthesis. Hence one may see what
wide vistas are opened up by the study of viruses towards an
understanding of the significance of nucleic acid derivatives
in the specific synthesis of proteins.
The tobacco mosaic virus, which has been obtained in
crystalline form, has been studied in detail by numerous
workers using the most dixerse and refined apparatus and
methods — by X-ray crystallographic analysis, with the elec-
tron microscope, with the ultracentrifuge, by the incorpora-
tion of labelled atoms, by chromatography, etc. (Fig. 22).
Until very recently indeed it was held that the nucleic acid
in tobacco mosaic virus was exclusively RNA, but a com-
munication has just appeared showing that in this virus, as
in several other viruses, there is a small amount of DNA.^^°
Thus, even from this point of view, the crystalline virus does
not seem to be a single substance.
As the investigations of R. Markham^" have shown, the
ribonucleic acids of tobacco mosaic virus, tomato bushy stunt
virus, turnip yellows mosaic virus, potato X virus and one of
the tobacco necrosis viruses are different from one another
in their composition and furthermore each of them differs
substantially from the ribonucleic acid of the respective host.
In the viruses ^vhich have been listed, the differences in
proportion of the nucleotides contained in their ribonucleic
acids are so great that they can serve as criteria for differen-
tiating between one of these viruses and another. The same
is true of the protein parts of the nucleoproteins of these
viruses.
The amino acid composition of the protein of tobacco
mosaic virus is fairly accurately worked out and is similar
to that of a globulin. At present 18 ' common ' amino acids
have been obtained from it ; they are without exception
L-isomers.^*^ The molecular weight of tobacco mosaic virus
particles is very high, about 40 million, but the fundamental
protein molecules which take part in the structure of the
virus have a molecular weight of about 17,000. This may be
demonstrated by destroying the virus Asith ultrasonic vibra-
tions or detergents. Similar values for the molectilar weights
of the fundamental proteins have also been obtained by
276 ORIGIN OF STRUCTURES AND FUNCTIONS
determining the numbers of terminal groups of the poly-
peptide chains. It has thus been established that the amino
acid at the carboxyl end of the chain is threonine. ^^^
All these data taken together indicate that the protein
component of the particle of tobacco mosaic virus consists
of about 2,800 separate peptide chains each of which has a
threonine residue at one end and is composed of up to 150
amino acid residues. These polypeptide chains are folded in
a definite way to form the fundamental molecule of the
protein of the virus.
Proteins of this kind are not only to be obtained from the
nucleoproteins of the virus, they may also be isolated from
the juices of the infected plant, where they exist in the free
state, not combined with nucleic acid. This was done by
W. N. Takahashi and M. Ishii."^ These authors isolated,
by electrophoresis, the same protein from the tissues of
tobacco, tomato and phlox plants infected with tobacco
mosaic virus and called it X-protein. It was found to be
different from the proteins of the plants in question, but to
correspond both chemically and serologically with the pro-
tein of the virus. In neutral solution the particles of this
protein are nearly the same size as the fundamental mole-
cules of the virus proteins but in an acid medium they join
together to give rod-shaped formations which look, under
the electron microscope, like virus particles and have a
diameter of 150 A. This protein is absent from healthy plants.
The suggestion that the X-protein is made up of fragments
of normal virus particles arising in the process of disintegra-
tion of the plant tissues has not been confirmed. On the
contrary, all the data now available indicate that it is the
immediate product of biosynthesis which takes place in the
living plant in the presence of the virus. The X-protein has
no infectivity and, accordingly, no power of self-reproduction
even within the living cell.
X-ray crystallographic studies^*^ of the virus particles have
shown that the axis of the cylinder or core of the rod is
formed by the nucleic acid while the protein is arranged
as a covering layer around it. The polypeptide chains of the
fundamental protein molecule are curled round the axis
of nucleic acid in such a way that the whole virus particle
Fh;. ti'Z. (:r\slals of loljacco mosaic \ irus in a leaf
(aficr Gol'diii).
Fig. 23. Virus particles from \vhich
the protein has been removed in
some places (after Schramm. Schu-
macher and Zilli^).
# =. >*
Fic.. 24. Tobacco mosaic virus showing nucleic acid
threads, rod-shaped particles and discs of protein whh
liolcs ill ihc middle (after Schramm. Schumacher and
Zillig).
BIOSYNTHESIS OF PROTEINS 277
may be compared with a necklace, the nucleic acid corre-
sponding with the thread and the fundamental protein
molecules with the beads (Fig. 23).
The work of H. Fraenkel-Conrat and R. C. Williams^^® was
a great achievement in the field of virology. These workers
succeeded not merely in separating the nucleic acid from
the protein components of tobacco mosaic virus, but also in
reassembling the virus from these components in a biologi-
cally active state. The authors cited lay special stress on the
need to retain the separate components absolutely in the
native state, if this is to be successful. In particular, it is
only by using the unaltered nucleic acid of a virus that
positive results can be obtained. When it has been treated
with ribonuclease it will no longer serve as material for the
assembly of a virus. Equally unsuccessful were attempts to
substitute for the RNA of tobacco mosaic virus DNA
obtained from the thyroid gland or RNA from the turnip
yellows virus.
The protein component which was separated from the
nucleic acid was found by electron microscopy to take the
form of discoid particles having a thickness of 50-150 A
and a diameter the same as that of the rod of the active virus
particle (150 A). In the centre of the disc a hole was found
having a diameter of about 40 A (see Fig. 24).
According to the authors quoted, these discs are in-
distinguishable from X-protein. When the active virus is
assembled, the protein discs combine with the nucleic acid,
which is concentrated in the central cavity and which
enables the fimdamental protein molecules to aggregate. As
a result of this aggiegation particles are formed which are
indistinguishable from the particles of the original virus.
They are thus about 3,000 A long.
The action of detergents on a reconstituted virus produces
the same deformation of the particles as in the original virus.
The rods are broken up into discs and at the site of the
fractures there are seen to be centrally disposed cores which
disappear on treatment with ribonuclease, thus showing that
they are made up of RNA.
According to Fraenkel-Conrat and Williams neither the
protein nor the nucleic acid by itself shows any sign of
278 ORIGIN OF STRUCTURES AND FUNCTIONS
infectivity. In a very recent experiment Fraenkel-Conrat^*^
assembled active virus particles from the protein of one strain
of virus and the nucleic acid of another. A particularly
interesting complex virus of this kind is obtained from the
protein of common tobacco mosaic virus and the nucleic
acid of the Holmes ribgrass strain of virus. This combination
is notable for the fact that the protein of tobacco mosaic virus
differs from that of the ribgrass virus both in amino acid
composition and in serological properties.
The complex virus thus obtained is inactivated by anti-
tobacco mosaic sera but not by anti-ribgrass. Furthermore,
plants infected with this complex, artificial virus form only
the nucleic acids and proteins characteristic of the ribgrass
virus. In particular, the protein contains methionine and
histidine which are characteristic of this virus.
These results are in complete agreement ^vith those of
A. Gierer and G. Schramm.^** In contradistinction to the
findings of Fraenkel-Conrat and Williams which have already
been described, Gierer and Schramm showed that the nucleic
acid of a virus, completely freed from protein, when intro-
duced into a tobacco plant ^vould evoke the formation of the
characteristic nucleoprotein of the virus.
This fact may be compared with earlier observations on
the infection of bacteria with the corresponding phages. In
their experiments A. D. Hershey and M. Chase^*® used
bacteriophage of group T which had been labelled with
phosphorus and sulphur. They showed that only the DNA
of the phage enters into the bacterium and evokes there the
formation of fresh virus while the protein stays outside the
cell of the host and therefore does not play a direct part in
the infection.
From the examples which have been given it is quite
obvious that in living cells there is no ' multiplication ' of
protein molecules, nor do they arise as a result of straight-
forward autocatalysis. In cells there occurs a complicated
biosynthetic process whereby new protein is formed, the
carrying out of ^\hich requires the participation of a large
number of complicated energic, catalytic and structural
systems ^vhich we have remarked on in the living body.
Nucleic acids with their definite intramolecular structure
BIOSYNTHESIS OF PROTEINS 279
occupy a very prominent place among these systems in deter-
mining the specific structure of any particular protein. In
Gale's experiments the addition of nucleic acid to structural
fragments of bacterial cells restored their ability to synthesise
particular proteins. Similarly, the introduction of the RNA
of tobacco mosaic virus into the leaves of tobacco plants
creates suitable conditions for the synthesis there by the
protoplasmic systems of the cell of the specific X-protein
which could not have been formed there before the infection
and which seems to be the result of distortions of the process
of biosvnthesis of protein, distortions determined by the
intramolecular structure of the viral nucleic acid.
The specificity of the viral RNA compared with other
similar nucleic acids consists simply in the fact that the viral
RNA can enter actively into the metabolism of the tobacco
plant and, to some extent, overcome the influence of the
nucleic acids of the plant itself and enable the leaf to syn-
thesise proteins which are foreign to it and which accumulate
there in very large and, therefore, easily detectable amounts.
It may be that more careful study would show that many other
nucleic acids could also alter, to some extent, the course of
biosynthesis in foreign organisms into which they were intro-
duced in the native state. In particular we are convinced
that the experiments, which have recently become widely
known, in which one strain of bacteria is transformed into
another under the influence of DNA prepared from the
latter, are cases in point.''"'
An understanding of the part played by the intramolecular
structure of nucleic acids in the biosynthesis of proteins with
specific structures was made more difficult until very recently
by the over-simplified hypotheses concerning the structure of
the nucleic acids themselves.
It is still not long since it was accepted, in accordance with
the results of P. A. Levene and R. S. Tipson"' that the
fundamental units of RNA and DNA consisted of tetra-
nucleotides, i.e. complexes composed of four appropriate
mononucleotides united w^ith one another. According to this
hypothesis the tetranucleotide complex of RNA is made up
of adenine nucleotide, guanine nucleotide, cytosine nucleo-
tide and uracil nucleotide while DNA is composed of adenine
28o ORIGIN OF STRUCTURES AND FUNCTIONS
desoxynucleotide, guanine desoxynucleotide, cytosine desoxy-
nucleotide and thymine desoxynucleotide. Such tetranucleo-
tides would have molecular weights of 1,300 for RNA and
1,250 for DNA. In fact, however, the values actually found
for the molecular weights of various ribonucleic acids ranged
from 10,000 to 300,000"^ and for desoxyribonucleic acids
from 500,000 to 1,000,000,^" or, according to later results,
up to 8,000,000,"* which suggested that nucleic acids are
high polymers of tetranucleotides. Naturally, in such poly-
mers the quantitative proportions of the various mono-
nucleotides and their spatial relations to one another would
remain unchanged. This created a very cramped framework
for possible variations in the intramolecular structure of
nucleic acids.
However, in the light of recent evidence, which is mainly
due to the work of E. Chargaff and his colleagues,"^ the tetra-
nucleotide theory of the structure of nucleic acids has been
overthrown. It is now accepted that RNA and DNA consist
of long chains, the individual links of which are mono-
nucleotides joined together by phosphoric acid residues
which combine with the hydroxyl groups of the ribose or
desoxyribose in the 3 and 5 positions, that is, to give bonds
of the type c3'.opo.C5'. The proportions of purine and pyri-
midine nucleotides and, even more important, their sequence
and orientation in the polynucleotide chain may vary, and
do in fact vary extremely widely, in nucleic acids of different
origins.
The evidence from X-ray crystallographic analyses carried
out by J. D. Watson and F. H. C. Crick"' suggests a model
for DNA which may be represented diagrammatically as in
Fig. 25.
According to this model, the molecule of desoxyribose
nucleic acid is composed of two spiral chains wound regularly
round a single common axis. Each chain consists of di-
esterified phosphate residues combined with ^-D-desoxyribo-
furanoside residues in the 3 and 5 positions. The purine and
pyrimidine bases lie within the helix while the phosphoric
groups are on the outside. The helical chains which make up
the molecule are joined together by the paired interaction of
the bases of one chain with those of the other. This pairing
BIOSYNTHESIS OF PROTEINS
281
is brought about by hydrogen bonds and the bases He in
planes perpendicular to the long axis of the molecule.
The three-dimensional structure of RNA is still not com-
pletely clear ; maybe its molecules have branched chains.
A structure of this kind would allow
of an unlimited number of isomers,
the individual characteristics of which
would be determined by the relative
arrangement of the nucleotides in the
chain/" It is clear that these possi-
bilities must be very widely realised
in the world of living things and, in
fact, we find there a tremendous
variety of nucleic acids with specific
structures, just as we do with
proteins
Fig. 25. Structural model of the
macromolecule of desoxyribonucleic
acid. Two spiral chains of desoxy-
ribose ; the horizontal lines represent
pairs of nitrogenous bases uniting the
chains by means of hydrogen bonds
(after Watson and Crick).
There is a whole series of experimental data demonstrating
the species specificity of nucleic acids and showing that the
DNA and apparently also the RNA of different species have
different over-all compositions.^^* Furthermore, w^e may
speak of organ specificity or tissue specificity which means
that different organs within the same organism have different
nucleic acids, and, finally, there is organelle specificity of
nucleic acids. This applies specially to RNA, on account of
its localisation in the various formed elements of protoplasm.
In particular, much evidence has been given in the literature
showing that the RNA of the nucleus and that of the cyto-
plasmic granules are different from one another."^
The view is widely maintained in contemporary scientific
literature that the molecule of nucleic acid with its specific
282 ORIGIN OF STRUCTURES AND FUNCTIONS
complementary arrangement of purine and pyrimidine mono-
nucleotides and polynucleotide chains is like a matrix in
which a particular protein can be synthesised. Each point
on the matrix has a specific affinity for a definite amino acid.
Thus, according to the hypothesis of P. C. Caldwell and C.
Hinshelwood,""" the amino acids crystallise, so to speak, on
the molecule of nucleic acid in a strictly determined order
corresponding with the structure of the matrix.
As the combination of amino acids into a polypeptide
chain requires the expenditure of a certain amount of energy,
it is generally accepted that the processes leading to the
synthesis of proteins on nucleic acids occur in the following
order :
Either the separate amino acids are activated by phos-
phorylation at the expense of adenosine triphosphate, or else
the RNA is itself phosphorylated and activated.^" The
amino acids are then bound to the appropriate points on
the nucleic acid. Later, when the full complement of amino
acids is present, peptide bonds are formed between them to
form ' pro-proteins '. Enzymes play an important part in
this process. When the ' pro-proteins ' have been formed they
become separated from the nucleic acids, a process which
may require a further expenditure of energy and the par-
ticipation of specific catalysts. This is the process which is
slowed down by chloramphenicol and aureomycin, substances
which have hardly any effect on the incorporation of amino
acids."'*"
G. Gamow""^ has recently tried to use his very ingenious
mathematical calculations to shoAV that the specific centres for
the combination of particular amino acids on the nucleic
acid matrix consist of strictly determined groups of three
nucleotides. If four different nucleotides in any nucleic acid
are taken in groups of three, the following variants are
possible: (1) all three components may be the same, or,
to use Gamow's card-playing terminology, they may belong
to the same ' suit ' ; (2) two components may be the same
Avhile the third belongs to a different ' suit ' ; (3) all the
components may be different. In this way the number of
possible variants will be 20, which corresponds with the
number of amino acids in proteins. As an example, Gamow
BIOSYNTHESIS OF PROTEINS
283
has tried to show that in tobacco mosaic \irus there is some
correlation between the content of nucleotides of the viral
RNA and that of amino acids of the viral protein. For
♦
W
c
/
/[■
y
N C \ /
H — C — H
\J M
W .0/
4
*
♦
0
w
/
N
-c
//
w
c
c ■
/ \
y
1
1
/
c
/
II "
H
/
N C
// w
\
c-
-/
H — C — H
H H— C -H
\
o-
\
Fig. 26. Triads of nucleotides (after Gamow).
example, valine is supposed to correspond to the combination
adenylic acid, cytidylic acid, uridylic acid, tyrosine to adeny-
lic, adenylic, adenylic acid, etc. However, if we do the same
calculations for turnip yellows virus, the correspondence
284 ORIGIN OF STRUCTURES AND FUNCTIONS
between the theory and the analytical evidence is less satis-
factory. A. L. Bounce considers that the specific arrange-
ment of the amino acids during the formation of a protein
is determined, not by triads, but by diads of nucleotides
(Fig. 26).
These suggestions certainly still require a lot more experi-
mental work, but many biologists and physicists are now
attracted to them. Owing to the attractiveness of the matrix
theory some authors are trying to resurrect the earlier theory
of the ' living molecule ', though it is no longer the protein
molecule which plays this part, for it is now quite clear that
this needs complicated systems for its biosynthesis. The part
has now been assumed by the molecule of nucleic acid, the
formation of which has not yet been studied.
In the scientific literature of to-day concerning nucleic
acid its individual molecules are endowed with the ability to
' reproduce themselves ', to ' divide ' and to ' multiply ' just
as were the molecules of protein yesterday. However, experi-
ence with the latter teaches us that we should regard with
caution such a priori and highly simplified ideas.*
It is first necessary to understand clearly that, in the
process of the biosynthesis of proteins, nucleic acid (especially
RNA) does not act as an independent entity, it is only a part
of a complicated apparatus. Without this apparatus nucleic
acid cannot synthesise protein on its own. This is indicated
by all the facts concerning the biosynthesis of proteins and,
in particular, by the experiments which we have already
discussed involving the very gentle disruption of the struc-
tures of isolated fragments of bacterial protoplasts deprived
of their envelopes simply by a slight lowering of the con-
centration of sucrose in the surrounding solution. When this
happens, there is no detectable chemical alteration in the
nucleic acids, they remain just as they were but the synthesis
of protein is arrested. This is because it requires not merely
the intramolecular structure of nucleic acid but also the
larger-scale structure of the formed elements of the proto-
plasm on which are ' assembled ' the enzymic systems which
determine the order and harmony of the energetic and syn-
* For a criticism of these views see C. C. Lindegren.204 — Author.
BIOSYNTHESIS OF PROTEINS 285
thetic reactions. In fact the kinetic conditions which are
very important for any biosynthesis, the relative rates of dif-
ferent processes, the organisation of protoplasm in space as
well as in time, give great flexibility to the biosynthesis. This
leads to the formation, not of individual proteins, the mole-
cules of which are identical with one another, but of extensive
families of proteins which are very like one another.
This would be hard to achieve by rigid synthesis on a
matrix. It would be as though the same type could be used
to print several newspapers which, although they were of the
same political persuasion, nevertheless had a different scope
and arrangement of their articles. This suggestion was also
discounted by Gamow in his latest paper. Gamow^"^ regards
the variability of the proteins which are synthesised as a
possible means of biological evolution, although he gives no
explanation of the mechanism of this phenomenon.
To pursue the typographical analogy, set type is needed
to form the matrix. What then corresponds to this type in
the living cell? How is the rigidly determinate arrangement
of nucleotides in the polynucleic matrix set up? As w^e have
seen above, there is a great deal of factual material which
indicates that RNA plays a direct part in the synthesis of
proteins. Although it is frequently found in the scientific
literature, there is less factual evidence for the idea that the
specific structure of RNA is in some way determined by the
DNA of the nucleus. To use the language now adopted by
physicists, the information concentrated in the molecules of
DNA is first passed on to the molecules of RNA, after which
the synthesis of protein molecules proceeds in accordance
w^ith the information which is relayed by the sequence of
nucleotides in the RNA chain. ^°®
However, even if we assume the truth of this hypothesis,
it does not carry us much further forward, for the question
now arises as to how^ the rigidly determinate arrangement of
nucleotides in the DNA was brought into being.
One can nowadays hardly take the view that DNA does
not take part in metabolic activities, does not undergo any
changes in the process of development of the cell, but merely
reproduces itself in such a way that each new molecule arises
directly by autocatalysis from a pre-existing molecule. This
286 ORIGIN OF STRUCTURES AND FUNCTIONS
is contradicted by numerous observations which show that,
during the process of development of cells, their DNA con-
tent may diminish markedly until it disappears completely,
as occurs in the unfertilised sea-urchin's egg.^"^ On the basis
of a study of the development of the mycelium of Actino-
myces globisporus streptomycini N. S. Demyanovskaya and
A. N. Belozerskii^"* have shown that at a definite develop-
mental stage DNA apparently disappears. In its place there
is found in the mycelium another nucleic acid containing not
thymine but another base, X. This acid is apparently a
precursor of DNA, which is later synthesised from it.
We still know very little about the biosynthesis of nucleic
acids but all the facts at our disposal suggest that it is no less
complicated a process than the biosynthesis of proteins and is
by no means a simple autocatalytic process of self-reproduc-
tion.
The studies on the enzymic synthesis of nucleic acid which
have recently been started by M. Grunberg-Manago and
others^°^ in S. Ochoa's laboratory are of very great interest
from this point of view. These workers used an enzyme isol-
ated from Azotobacter which catalyses the synthesis of poly-
nucleotides from nucleoside-5'-diphosphate with the libera-
tion of inorganic orthophosphate according to the equation:
n(A— R— P— P)^^(A— R— P)„ -f r?P
A = the base, R = ribose, P = pliosphoryl radical.
One may thus suppose that the reaction whereby poly-
nucleotides are formed, like that whereby polysaccharides are
formed, is a process of reversed phosphorolysis. The authors
therefore called their enzyme ' polynucleotide phosphoryl-
ase '. They showed that it was possible, by using this enzyme,
to synthesise a substance similar to ribonucleic acid from
separate mononucleotides. From this it follows that the bio-
synthesis of nucleic acids, like that of the other compounds
found in protoplasm, is brought about by means of a compli-
cated enzymic apparatus. Thus, on the one hand, the synthesis
of proteins requires the presence of nucleic acids while, on
the other, the synthesis of nucleic acids requires the presence
of proteins (enzymes).
BIOSYNTHESIS OF PROTEINS 287
J. D. Bernal has recently come to the same conchision on
the basis of his work ^vith viruses. At the end of his address
on this subject to the Moscow State University in 1955 Bernal
asked me the following question: In this case, which came
first, nucleic acids or proteins?
This question reminds one somewhat of the scholastic
problem about the hen and the egg. The problem is insoluble
if we approach it metaphysically in isolation from the whole
previous history of the development of living matter. Nowa-
days e\ery hen comes from an egg and every hen's egg from
a hen. Similarly, nowadays proteins can only arise on the
basis of a system containing nucleic acids while nucleic acids
are formed only on the basis of a protein-containing system.
The hen and its egg developed from less highly organised
living things in the course of their evolution. In the same
way, both proteins and nucleic acids appeared as the result
of the evolution of whole protoplasmic systems which devel-
oped from simpler and less well adapted systems, that is to
say, from whole systems and not from isolated miolecules. It
would be qtiite wrong to imagine the isolated primary origin
either of proteins or of nucleic acids.
Many contemporary authors do, however, follow this line
of thought. They take the view that in the first place nucleic
acids arose in some way and that at once, simply by virtue
of their intramolecular structure, they Avere able both to syn-
thesise proteins and to multiply themselves spontaneously.
It is, however, clear from all our previous discussion that a
hypothesis of this sort is in direct opposition to the facts as
they are at present known.
An interesting attempt to bring these hypotheses into line
with contemporary scientific data is to be foimd in the
lecture given by L. Roka at a colloquium on comparative
biochemistry in April 1955 in Mosbach-Baden.^^° He gave
a clear account of the fact that the synthesis of nucleic
acids requires the presence of a complicated organisation of
metabolism and then put forward the suggestion that this
metabolism first arose simply in the waters of the primaeval
ocean.
The transformation of polyphosphoric acid in these waters
also gave rise to the ' original matrix ', the molecule of
288 ORIGIN OF STRUCTURES AND FUNCTIONS
nucleic acid. Nucleic acid, reproducing itself and forming
proteins in conjunction with the metabolism of the ocean
itself, also constitutes, according to Roka, 'living protoplasm'.
By degrees more and more ' living protoplasm ' ^vas formed
while the surrounding medium became more and more ' life-
less ' until eventually the process culminated in the formation
of the first organisms.
This schematic description is, however, open to a number
of objections. In the first place, it is hard to imagine the
development of metabolism simply within the aqueous solu-
tion of the primaeval ocean. Metabolism is not merely the
conjunction of various reactions co-ordinated to some extent
in time. In organisms of the present day, metabolism is a
definite organisation of processes directed to^vards the con-
tinuous self-preservation and self-reproduction of the living
system as a whole. Such an organisation could only have
been built up by natural selection and selection requires
circumscribed individual formations and could not take
place in a homogeneous solution. This is the first point ; the
second is that although Roka's outline, which we have
discussed in Chapter V, demonstrating the possibility that
polynucleotides may be formed by the transformation of
polyphosphoric acids seems very probable and apposite it
still does not solve the question of the origin of nucleic acid
itself. This latter is distinguished from simple polynucleo-
tides in that the arrangement of the mononucleotides in its
chain is strictly determined and its biological role in the
synthesis of proteins depends on its three-dimensional intra-
molecular structure. This is, of course, the very property
which requires explanation and Roka passes it over in silence.
Reference to the ' happy chance ' that, out of many billions
and quadrillions of combinations there could have been
formed by chance just that indispensable sequence which is
required for the synthesis of proteins is just as irrational in
this case as were earlier references to the ' chance ' formation
of proteins (enzymes). Not only is the structure of these
proteins very complicated but it is extremely thoroughly
adapted to the performance of definite catalytic functions
which play an important part in the life of the ^vhole organ-
ism, it is inwardly ' constructed for its purpose '. Such
BIOSYNTHESIS OF PROTEINS qSq
adaptation to its biological function, such ' purposeful '
structure, is also characteristic of the nucleic acids of present-
day organisms and its origin by chance is as impossible as
the chance assembly from its elements of a factory capable
of turning out any particular product.
The third and final point is that, even if we admit for a
minute the possibility that in the primaeval soup of the
ocean there might have arisen by chance molecular matrices
which could reproduce themselves incessantly, even then life
could not arise on this basis. In such a case the matrix would
continually produce nothing but molecules exactly like itself
and the primary organic material would simply be converted
into uniform layers of nucleic acids or deposits similar to the
' mineral formations ' of crystallised organic materials.
The molecule of nucleic acid in contemporary living
organisms is not an independent ' living molecule ', it is only
a part of living protoplasm, an organ of that protoplasm
subserving a function necessary for life. Thus, all that we
have already said about the origin of proteins or enzymes
applies equally to nucleic acids.
Contemporary scientists are also quite right in supposing
that the development of matter proceeded from simpler to
more complicated systems. Nevertheless, although the separ-
ate organs, such as an arm or an eye, are simpler than the
whole organism, we should not assume, like Empedocles,
that higher living things developed by the aggregation of
separate organs. Danvin has shown us the true way in which
these living organisms arose. This way is through the evolu-
tion of more simply organised things, the evolution of com-
plete systems brought about by natural selection.
Similarly it would be wrong to suppose that there first
arose proteins, nucleic acids and the other complicated
substances found in protoplasm, which had intramolecular
structures which were extremely well and efficiently adapted
to the performance of particular biological functions, and
that living protoplasm itself arose as the result of a combina-
tion of these substances.
All that we can expect from the relatively simple thermo-
dynamic and kinetic laws which prevailed on the surface of
the primaeval Earth is that they should explain the formation
19
290 ORIGIN OF STRUCTURES AND FUNCTIONS
of organic polymers in the shape of polypeptides and poly-
nucleotides, assemblages having, as yet, no orderly arrange-
ment of amino acid and nucleotide residues adapted to the
performance of particular functions.
These polymers were, nevertheless, able to form multi-
molecular systems, though these were undoubtedly in-
comparably simpler than living protoplasm. It is only by
the prolonged evolution of these systems, their interaction
with their environment and their natural selection that there
developed the forms of organisation characteristic of the
living body: metabolism, proteins, nucleic acids and other
substances with complicated and ' purposeful ' structures
which characterise the contemporary living organism.
BIBLIOGRAPHY TO CHAPTER VI
1. H. M. RouELLE. Recueil periodique d' observations de
medecine de chirurgie et de pharmacie, 40, 59 (1773).
A. F. FouRCROY. Ann. Chun. (Phys.), 5, 252 (1789).
2. G. J. Mulder. /. prakt. Cheni., 16, 129 (1839).
M. V. Tracey {Proteins and life. London, 1948) and H.
Hartley {Nature, Lond., 168, 244 (1951)) cite earlier
Netherlands publications by Mulder using this term.
Hartley also gives evidence that it had been suggested
to Mulder by J. J. Berzelius.
3. H. voN MoHL. Grundzilge der Anatomie und Physiologie
der vegetahilischen Zelle. Braunschweig, 1851 ; Bot
2^^:^.73.89(1846).
4. (I. 60).
5. F. Engels. Herr Eugen Dilhring's revolution in science.
[Anti-Diihring.] (trans. E. Burns). London, 1934 ;
Ludwig Feuerhach and the outcome of classical Ger-
man philosophy (ed. C. P. Dutt). London (Martin
Lawrence, undated).
6. F. Engels. Herr Eugen Dilhring's revolution in science.
[Anti-Diihring.] (trans. E. Burns). London, 1934.
7- (I- 59)-
8. E. Pfluger. Pfliig. Arch. ges. Physiol., 10, 251 (1875).
9. F. BoTTAzzi in Handbuch der vergleichenden Physiologie
(ed. H. Winterstein). Vol. 1 (1st half), p. i. Jena,
1911.
10. N.N.IwANOFF. Bzoc/zem.Z., 7(52, 441 (1925).
BIBLIOGRAPHY QQl
11. H. G. DoFFiN. Le roman de la molecule: I' explication
de la vie. Saint-Germain-en-Laye, 1953.
12. M. Verworn. Allgemeiyie Physiologie. Jena, 1909.
13.(111.47).
14. R. L. M. Synge. Biokhimiya, 10, 179 (1945) ; Royal
Institute of Chemistry : Lectures, Monographs and
Reports, 1952, No. 1.
15. N. W. PiRiE. Biol. Rev., i^, 377 (1940).
16. E. J. CoHN, D. M. SuRGENOR and M. J. Hunter in Enzymes
and enzyme systems : their state in nature (ed. J. T.
Edsall), p. 105. Cambridge, Mass., 1951.
17. R. J. Block in The chemistry of the amino acids and pro-
teins (ed. C. L. A. Schmidt), p. 278. Springfield, 111.,
1938.
18. A. TisELius and I.-B. Eriksson-Quensel. Biochem. J., }^,
1752 (1939)-
19. J. T. Edsall. Advanc. Protein Chem., ^, 383 (1947).
20. T. L. McMeekin in The proteins (ed. H. Neurath and K.
Bailey). Vol. 2A, p. 389. New York, 1954.
21. J. F. Taylor in The proteins (ed. H. Neurath and K.
Bailey). Vol. 7^4^ p. 1. New York, 1953.
22. G. R. Tristram in The proteins (ed. H. Neurath and K.
Bailey). Vol. 7.4, p. 181. New York, 1953.
23. C. H. Li. /. Amer. chem. Soc, 68, 2746 (1947).
T. L. McMeekin, B. D. Polis, E. S. Dellamonica and J. H.
Custer. /. Amer. chem. Soc, yo, 88i (1948).
24. V. N. Orekhovich. Priroda, 19^6, no. 5, p. 35.
25. H. Brown, F. Sanger and R. Kitai. Biochem. J., 60, 556
(1955)-
26. J. B. Sumner and G. F. Somers. Chemistry and methods of
enzymes (2nd edn.). New York, 1947.
27. A. Ya. Danilevskii. Fiziologicheskii Sbornik, i, 289 (1888) ;
2, 281, 291 (1891). Khar'kov (Tip. Zil'berberga).
28. E. Fischer. Ber. dtsch. chem. Ges., ^^, 1095 (1902).
29. F. Hofmeister. Ergebn. Physiol., i (Abt. 1), 759 (1902).
30. H. RiTTHAUSEN. Die Eiivesskorper der Getreidearten,
Hiilsenfriichte und Olsamen. Bonn, 1872.
31. H. B. Vickery. Ann. N.Y. Acad. Sci., ^j, 63 (1946).
32. W. H. Stein. A?m. N.Y. Acad. Sci., ^y, 59 (1946).
33. T. B. Osborne. The vegetable proteins. London, 1909.
34. A. J. P. Martin and R. L. M. Synge. Advanc. Protein
Chem., 2, 1 (1945)
35. D. Shemin. /. biol. Chem., 1^9, 439 (1945). /\^^}^L .
292 ORIGIN OF STRUCTURES AND FUNCTIONS
36. A. S. Keston and S. Udenfriend. Cold Spr. Harb. Symp.
quant. Biol., i^, 92 (1950).
37. E. E. Snell. Advanc. Protein Chern., 2, 9>f) {\(^^&).
38. S. Moore and W. H. Stein. /. biol. Chem., i']8, 53 (1949) ;
192, 663 (1951).
39. P. Desnuelle in The proteins (ed. H. Neurath and K.
Bailey). Vol. lA, p. 87. New York, 1953.
40. H. B. ViCKERY and C. L. A. Schmidt. Chem. Rev., p, 169
(1931)-
41. E. Chain. Ann. Rev. Biochem., ly, 657 (1948).
42. E. Work. Biochem. J., 49, I'j (iq^i).
43. E. Bricas and C. Fromageot. Advanc. Protein Chem., 8, 1
(1953)-
44. E. Bricas and C. Fromageot. Advanc. Protein Chem., 8, 1
(1953)-
S. G. Waley. /. chem. Soc, 1955, p. 517.
45. R. D. HoTCHKiss. /. biol. Chem., 141, 171 (1941).
46. R. L. M. Synge. Biochem. J., 59, 363 (1945).
47. A. H. Gordon, A. J. P. Martin and R. L. M. Synge,
Biochem.]., ^y, 9,19, (1943).
48. J. T. Holden and E. E. Snell. /. biol. Chem., i']8, 799
(1949)-
49. D. RiTTENBERG and D. Shemin. Ann. Rev. Biochem., 1$,
247 (1946).
50. K. Bailey. Chem. and Ind., i^, 243 (1950)-
51. K. Felix and A. Mager. Hoppe-Seyl. Z., 249, 111 (1937).
52. M. Bergmann. Chem. Rev., 22, 423 (1938).
53. C. Niemann. Cold Spr. Harb. Symp. quant. Biol., 6, 58
(1938)-
54. G. F. Gauze and M. G. Brazhnikova in Sovetskii gramit-
sidin i lechenie ran (ed. P. G. Sergiev), p. 5. Moscow
(Medgiz), 1943.
55. A. N. Belozerskii and T. S. Paskhina. Biokhimiya, 10,
344 (1945)-
56. R. Consden, a. H. Gordon, A. J. P. Martin and R. L. M.
Synge. Biochem. J., 41, 596 (1947)-
R. L. M. Synge. Biochem. J., 42, 99 (1948).
R. ScHWYZER and P. Sieber. Angeiu. Chem., 68, 518 (1956).
57. A. Paladini and L. C. Craig. /. Amer. chem. Soc, y6, 688
(1954)-
T. P. King and L. C. Craig. /. Amer. chem. Soc, yy, 6627
(1955)-
BIBLIOGRAPHY 293
58. L. C. Craig. Conferences et Rapports, j-eme Congres inter-
jiational de Biochimie, Bruxelles, 1-6 Aoiit 19^^, p.
416. Liege, 1956.
59. C. Fromageot. Cold Spr. Harb. Symp. quant. Biol., i^, 49
(1950).
60. F.Sanger. Nature, Lond., 162, /^^i [k^^^).
F. Sanger and H. Tuppy. Biochem. J., ^g, 463, 481 (1948).
F. Sanger and E. O. P. Thompson. Biochem. ]., 55, 353,
366 (1953)-
61. A. P. Ryle, F. Sanger, L. F. Smith and R. Kitai. Biochem.
].,6o, 541 (1955).
62. C. Tanford and J. Epstein. /. Amer. chem. Soc, y6, 2170
(1954)-
63. V. Du ViGNEAUD. Conferences et Rapports, ^-eme Congres
international de Biochimie, Bruxelles, 16 Aout 19^^,
p. 49. Liege, 1956.
64. P. H. Bell and R. G. Shepherd. Ibid., p. 10.
65. O. HoFFMANN-OsTENHOF. Euzy uiologie. Vienna, 1954.
66. W. Langenbeck. Die organischen Katalysatoren und ihre
Beziehungen zu den Fermenten (2 Aufl.). Berlin, 1949.
67. K. LoHMANN and P. Schuster. Biochem. Z., 2p^, 188 (1937).
68. D. E. Green, D. Herbert and V. Subramanyan. /. biol.
Chem., 138,^2^ (1941)-
F. KuBowiTZ and W. Luttgens. Biochem. Z., ^oy, 170
(1940-
69. O.Warburg. A^aafnf/55.^ ./o^ 493 (1953).
70. H. Theorell and A. C. Maehly. Acta chem. scand., 4,
422 (1950)-
A. C. Maehly in Enzymes and enzyme systems : their state
in nature (ed. J. T. Edsall), p. 77. Cambridge, Mass.,
1951-
71. B. Chance in The e?izy mes (ed. J. B. Sumner and K. Myr-
biick). Vol. 2, Part 1, p. 428. New York, 1951.
72. K. G. Stern. /. biol. Chem., 112, 661 (1936).
73. A. E. Braunshtein. Uspekhi biologicheskoi Khimii, i, 21
(1950)-
74. (VL 26).
75. P. Desnuelle. Advanc. ErizymoL, i^, 261 (1953).
76. F. Haurowitz. Chemistry and biology of proteins. New
York, 1950.
77. R. R. Porter in The proteins (ed. H. Neurath and K.
Bailey). Vol. /B, p. 973. New York, 1953.
78. J. F. Ambrose, G. B. Kistiakowsky and A. G. Kridl. /.
Amer. chem. Soc, y^, 1232 (1951).
294 ORIGIN OF STRUCTURES AND FUNCTIONS
79. R. M. Herriott. Advanc. Protein Chem., ^, 169 (1947).
80. H. Fraenkel-Conrat. Arch. Biochem., 2^, 109 (1950).
8i. R. M. Herriott in Symposium on the mechanism of enzyme
action. (McCoUura-Pratt Inst., Johns Hopkins Univ.)
(ed. W. D. McElroy and B. Glass), p. 24. Baltimore;
Md., 1953.
82. I. B. Wilson. Biochim. biophys. Acta, y, 466 (1951).
83. H. Neurath and G. W. Schwert. Chem. Rev., 46, 69
(1950)-
84. P. V. Afanas'ev. O prirode i kinetike fermentativnykh
protsessov. Diss. Moscow, 1950 ; Biokhimiya, 14, 259
(1949)-
P. V. Afanas'ev. Izvest. Akad. Nauk S.S.S.R., Ser. Biol., ^,
254 (1949)-
85. S. E. Bresler, Trudy soveshchaniya po probleme belka,
p. 63. Kiev (Izd. Akad. Nauk Ukr. S.S.R.), 1955.
86. M. P. Znamenskaya, P. A. Agatov and A. N. Belozerskii.
Doklady Akad. Nauk S.S.S.R., ^p, 95 (1948).
87. R. Acher, M. Jutisz and C. Fromageot. Biochim. biophys.
Acta, 8, 442 (1952).
R. Acher, U. R. Laurila, J. Thaureaux and C. Fromageot,
Biochim. biophys. Acta, 14, 151 (1954).
88. K. Ohno. /. Biochem., Japan, 41, 345 (1954).
89. A. R. Thompson. Biochem. ]., 61, 253 (1955).
90. C. B. Anfinsen, R. R. Redfield, W. L. Choate, J. Page
and W. R. Carroll. /. biol. Chem., 20'], 201 (1954)-
C. H. W. HiRS, S. Moore and W. H. Stein. /. biol. Chem.,
219, 613 (1956).
J. L. Bailey, S. Moore and W. H. Stein. /. biol. Chem.,
22/. 143 (1956)-
C. H. W. HiRs, W. H. Stein and S. Moore. /. biol. Chem.,
221, 151 (1956).
91. A. G. Pasynskii and V. A. Belitser. Uspekhi sovremennoi
Biol., ^6, 2^6 (1953)-
92. K. Thomas and J. Kapfhammer. Ber. sdchs. Akad. Wiss.
(Math-phys. Klasse), yy, 181 (1925).
93. L. Pauling. /. Amer. chem. Soc, 62, 2643 (1940).
94. (VI. 76).
95. F. W. Putnam in The proteins (ed. H. Neurath and K.
Bailey). Vol. iB, p. 807. New York, 1953 ; Advanc.
Protein Chem., 4, 79 (1948).
96. V. A. Belitser. Uspekhi biologicheskoi Khimii, i, 53
(1950).
BIBLIOGRAPHY 295
97. H. Wu. Chinese J. Physiol., ^, ^21 {ig^i).
98. A. E. MiRSKY and L. Pauling. Proc. nat. Acad. Sci.j Wash.,
22.439 (1936).
99. F. Haurowitz. KolloidzscJir., "ji, 198 (1935).
100. (VI. 79).
lOL F. Haurowitz and S. Tekman. Biochim. biophys. Acta, i,
484 (1947)-
102. J. Roche and M. Mourgue. Bull. Soc. Chim. biol., ^o, 322
(1948)-
103. C. H. Li. 7. Amer. chem. Soc, 6j, 1065 (1945).
104. L. Paulixg and R. B. Corey. Proc. nat. Acad. Sci., Wash.,
31' 251 (1950-
105. A. N. Bakh and A. I. Oparin in Sbornik rabot po chistoi
i prikladnoi khimii, p. 217. Moscow (NTO VSNKh),
1925. cf. Chem. Abstr., 20, 2337 (1926).
106. F. Haurowitz and F. Bursa. Rev. Fac. Sci. Univ. Istanbul,
loB, 283 (1945)-
107. J. O. Erickson and H. Neurath. /. exp. Med., yS, i (1943).
108. D. M. Wrinch. Nature, Lond., I ^y, 4_\\ {if^'^'o).
log. S. E. Bresler and D. L. Talmud. Doklady Akad. Nauk
5.S.S.i?.,^5,326(i944).
D. L. Talmud. Uspekhi biologicheskoi Khimii, i, 70 (1950).
110. A. G. Pasynskii and V. A. Belitser. Uspekhi sovremennoi
Biol., ^6,2^6 (1953)-
111. J. D. Bernal, I. Faxkuchen and D. P. Riley. Nature,
Lond., 142, 1075 (1938).
J. D. Bernal and I. Fankuchen. /. gen. Physiol., 2^, 111
(1941)-
R. B. Corey. Advanc. Protein Chem., 4, 385 (1948).
112. S. E. Darmon and G. B. B. M. Sutherland. /. Amer. chem.
Soc, 6c,, 20^4 (1947)-
E. J. Ambrose and A. Elliott. Proc. Roy. Soc, Lond.,
205^,47 (1951).
113. B. W. Low in The proteins (ed. H. Neurath and K. Bailey).
VoL lA, p. 235. New York, 1953.
114. (V. 175).
115. L. Pauling^ R. B. Corey and H. R. Branson. Proc. nat.
Acad. Sci., Wash., jy , 205 (1951)-
L. Pauling and R. B. Corey. Proc. nat. Acad. Sci., Wash.,
31> 235, 729 (1950-
116. (in. 50).
117. A. G. Pasynskii. Doklady Akad. Nauk S.S.S.R., yy, 863
(1951)-
296 ORIGIN OF STRUCTURES AND FUNCTIONS
118. SiMPLicius on Aristotle's De Caelo, 586, 29 (see H. Diels
Die Fragmejite der Vorsokraiiker. (2 Aufl.), Vol. 1,
p. 190 (Empedokles, B57). Berlin, 1906.) English
translation by K. Freeman. Ancilla to the pre-Socratic
philosophers. Oxford, 1952.
119. (III. 78).
120. M. KuNiTz and J. H. Northrop. /. gen. Physiol., ip, 991
(1936).
121. E. W. Davie and H. Neurath. /. biol. Chem., 212, 515
(1955)-
122. R. M. Herriott. J. gen. Physiol., 20, 335 (1937) ; 21, 501
(1938) ; 25, 185 (1941).
123. Zh. a. Medvedev. Uspekhi sovremennot Biol., 40, 159
(1955)-
124. F. Lipmann. Advanc. Enzymol., 6, 231 (1946) ; Fed. Proc,
<^. 597 (1949)-
125. A. E. Braunshtein. Trudy IV Sessii Akad. med. Nauk
S.S.S.R., p. 202. Moscow (Izd. AMN SSSR), 1948.
126. H. Chantrenne. Nature, Land., 160, 603 (1947) ; Biochim.
biophys. Acta, ^, 484 (1950).
127. A. E. Braunshtein, G. A. Shamshikova and A. L. Ioffe.
Biokhimiya, i^, 95 (1948).
128. P. J. DuRKiN and F. Friedberg. Biochim. biophys. Acta,
9> 105 (1952).
129. S. Yanari, J. E. Snoke and K. Bloch. /. biol. Chem., 201,
561 (1953)-
130. E. F. Gale and J. P. Folkes. Nature, Lond., 775, 1223
(1954); Biochem. J., 59,661 (1955).
131. F. B. Shtraub (Straub). Priroda, 1956, no. 2, p. 38.
132. H. BoRSOOK. Conferences et Rapports, ^-eme Congres inter-
national de Biochimie, Bruxelles, 1-6 AoUt 1955, p-
92. Liege, 1956.
133. S. E. Bresler. Uspekhi sovremennot Biol., ^o, 90 (1950).
134. R. B. Khesin. Biokhimiya, 18, 462 (1953) ; 19, 407 (1954)-
135. A. Danilevskii. Organoplasticheskie sily organizma. Khar-
kov (Tip. Zil'berberga), 1886.
W. W. Sawjalow. Pfliig. Arch. ges. Physiol., 85, 171 (1901).
136. H. Wasteneys and H. Borsook. Physiol. Rev., 10, 110
(1930)-
137. P. G. EcKER. J. gen. Physiol, 50, 399 (1947)-
A. I. ViRTANEN. Makromol. Cherri., 6, 94 (1951)-
138. J. H. Northrop. /. gen. Physiol., ^o, 377 (1947).
139. H. Tauber. /. Amer. chem. Soc, yi, 2952 (1949).
BIBLIOGRAPHY 297
140. M. Brenner, H. R. Muller and R. VV. Pfister. Helv.
chim. Acta, 55, 568 (1950).
141. M. Bergmann and H. Fraenkel-Conrat. /. biol. Chem.,
119, 707 (1937).
J. S. Fruton. Advanc. Protein Chem., ^, 1 (1949).
142. J. DuRELL and J. S. Fruton. /. biol. CJiem., 207, 487 (1954).
143. C. S. Hanes, F. J. R. HiRD and F. A. Ishervvood. Nature,
Lond., 166, 288 (1950).
144. C. S. Hanes, F. J. R. Hird and F. A. Isherwood. Biochem.
J.,^i, 25 (1952).
145. I. L. Kaganova and V. N. Orekhovich. Doklady Akad.
Nauk S.S.S.R., 93, 875 (1953) ; 95, 1259 (i954)-
146. F. Haurowitz. Qiiart. Rev. Biol.,24,<^'3, {\(^^(^).
147. A. L. Bounce, M. Morrison and K. J. Monty. Nature,
Lo7id., 176, P,Q^ (ig^rj).
148. R. Altmann. Studieji iiber die Zelle. Leipzig, 1886.
149. G. Lewitsky. Ber. dtsch. bot. Ges., 28, 538 (1910).
150. A. GuiLLiERMOND. C.R. Soc. BioL, Paris, 8^, 466 (1921).
151. E. W. MacBride and H. R. Hewer in Recent advances in
7nicroscopy : biological applications (ed. A. Piney).
London, 1931.
152. E. S. Horning. Ergebn. Eyizymforsch., 2, 336 (1933).
153. A. I. Oparin (Oparine). Variations de I'activite des enzymes
dans la cellule vegetale sous I'effet des facteurs ex-
terieurs. Rapport au deuxieme Congres international
de Biochimie, Paris, 19^2. Moscow (Izd. AN SSSR),
1952-
154. M. R. J. Salton. Biochim. biophys. Acta, 10, 512 (1953)-
155. M. Beljanski. Biochi7n. biophys. Acta, j$, 42^, {ig^4).
156. A. I. Oparin, N. S. Gel'man and N. G. Zhukova. Doklady
Akad. Nauk S.S.S.R., 10^, 1036 (1955).
157. N. M. SiSAKYAN. Fermentativnaya aktivnost' protoplazmen-
nykh struktur. Moscow (Izd. AN SSSR), 1951.
(Sissakian). Conferences et Rapports, ^-eme Congres inter-
national de Biochimie, Bruxelles, 16 Aoiit 1933, p-
18. Liege, 1956.
158. O. Lindberg and L. Ernster. Chemistry and physiology of
mitochondria and microsomes. In Protoplasmatologia
(ed. L. V. Heilbrunn and F. Weber). Bd. III/A/4.
Vienna, 1954.
159. W. C. Schneider. Conferences et Rapports, yeme Congres
international de Biochimie, Bruxelles, 1-6 Aout 1933,
p. 305. Liege, 1956.
298 ORIGIN OF STRUCTURES AND FUNCTIONS
160. K. Lang. Microskopische und chemische Organisationen
der Zelle. 2 Colloquium der deutschen Gesellschaft
fiir physiologische Cliemie. Berlin, 1952.
i6i. D. E. Green, W. F. Loomis and V. H. Auerbach. /. biol.
Chem., i'j2, 389 (1948).
162. W. C. Schneider and G. H. Hogeboom. /. biol. Chem.,
198, 155 (1952).
J. S. Roth. /. biol. Chem., 208, 181 (1954).
163. R. M. S. Smellie, W. McIndoe, R. Logan, J. N. Davidson
and L M. Dawson. Biochem. J., 5^, 280 (1953).
164. T. Caspersson. Naturwiss., 2g, 33 (1941).
165. J. Hammerling. Roux Arch. EntioMech. Organ., i^i, 1
(1934)-
166. J. Brachet and H. Chantrenne. Nature, Lond., 168, 950
(1951)-
167. J. Brachet and R. Jeener. Enzymologia, 11, 196 (1944).
168. T. Hultin. Exptl. Cell Research, i, 376 (1950).
169. E. B. Keller. Fed. Proc, 10, 206 (1951).
170. P. SiEKEViTZ and P. C. Zamecnik. Fed. Proc, 10, 246 (1951).
171. P. SiEKEViTZ. /. biol. Chem., ip^, 549 (1952).
172. J. Bracket. Symp. Soc. exp. Biol., 6, 173 (1952) ; in
Medecine et biologic No. 5 ; Un symposium sur les
proteines (general editor, M. Florkin). Liege and
Paris, 1947.
172a. N. M. SiSAKYAN. In Trudy i-go simpoziuma po voznik-
noveniyu zhizni. Moscow (Izd. AN SSSR), 1957.
173. R. Jeener and D. Szafarz. Arch. Biochem., 26, 54 (1950).
174. J. Brachet in Tlie nucleic acids (ed. E. Chargaff and J. N.
Davidson). Vol. 2, p. 475. New York, 1955 ; (Zh.
Brashe) Uspekhi sovremennoi Biol., 2g, 140 (1950).
175. M. Steinert. Bull. Soc. Chim. biol., Paris, ^^, 549 (1951).
176. S. Spiegelman and M. D. Kamen. Science, 10^, 581 (1946).
177. D. IvANOVSKii. Sel'skoe Khozyaisivo i Lesovodslvo, 18^2,
Feb., Otd. 2, p. 103 ; Mozaichnaya bolezn' labaka.
Moscow (Medgiz), 1949.
178. W.M.Stanley. Science^ (?/^ 644 (1935).
179. K. Sukhov. Rastitel'nye virusy. Moscow (Izd. AN SSSR),
1956-
L. Zil'ber. Uchenie o virusakh. Moscow (Medgiz), 1956.
P. Fildes and W. E. van Heyningen (ed.). Nature of virus
multiplication. (Symposium of Society for General
Microbiology.) London, 1953.
G. Schramm. Advanc. Enzymol., 1$, 449 (1954).
BIBLIOGRAPHY QQQ
180. M. HoLDEN and N. W. Pirie. Biocheyn. ]., 60, 46 (1955).
181. R. Markham. Cold Spr. Harb. Symp. quant. Biol., 18, 141
(1953)-
182. C. A. Knight. Advances in virus research, 2, 153 (1954).
183. H. Fraenkel-Conrat and B. Singer. /. Amer. cheni. Soc,
76, 180 (1954).
184. W. N. Takahashi and M. Ishii. Amer. J. Bot., 40, 85
(1953)-
185. J. D. Bernal. Lecture to Moscow State University, 1955.
186. H. Fraenkel-Conrat and R. C. Williams. Proc. nat. Acad.
Sci., Wash., 41, 690 (1955).
J. A. LippiNCOTT and B. Commoner. Biochim. biophys.
Acta, ip, 198 (1956).
R. G. Hart. Nature, Lond., lyy, 130 (1956).
187. H. Fraenkel-Conrat. /. Amer. chem. Soc, ']8, 882 (1956).
188. A. GiERER and G. Schramm. Z. Naturforsch., iiB, 138
(1956)-
189. A. D. Hershey and M. Chase. /. gen. Physiol., ^6, 39
(1952).
190. O. T. Avery, C. M. MacLeod and M. McCarty. /. exp.
Med., yg, 137 (1944)-
A. Boivin, a. Delaunay, R. Vendrely and Y. Lehoult.
Experientia, i, 334 (1945)-
R. D. Hotchkiss. Cold Spr. Harb. Symp. quant. Biol., 16,
457 (1950-
A. N. Belozerskh, A. S. Spirin, D. G. Kudlai and A. G.
Skavronskaya. Biokhimiya, 20, 686 (1955).
191. P. A. Levene and R. S. Tipson. /. biol. Chem., lop, 623
(1935)-
P. A. Levene. /. biol. Che??!., 126, 63 (1938).
192. H. S. LoRiNG. /. biol. Chem., 128, Ixi (1939) ; Fed. Proc,
6,4^1 (1947)-
S. S. Cohen and W. M. Stanley. /. biol. Chem., 144, 589
(1942).
E. R. M. Kay and A. L. Bounce. /. Amer. chem. Soc, y^,
4041 (1953)-
193. R. Signer, T. Caspersson and E. Hammarsten. Nature,
Lond., 141, 122 (1938).
194. S. Katz. /. Amer. chem. Soc, 74, 2238 (1952).
195. E. Chargaff. Symposium sur le metabolisme microbie?i,
p. 41. (2eme Congres international de Biochimie,
Paris, 21-27 Juillet, 1952). Paris, 1952.
196. J. D. Watson and F. H. C. Crick. Nature, Lond., lyi, "j^^j
964 (1953)-
300 ORIGIN OF STRUCTURES AND FUNCTIONS
197. A. N. Belozerskii and A. S. Spirin. Uspekhi sovremennot
Biol., 41, 144 (1956).
198. E. Chargaff and R. Lipshitz. /. Amer. chem. Soc, y^, 3658
(1953)-
199. A. Marshak. /. biol. Chem., i8g, 607 (1951).
200. P. C. Caldwell and C. Hinshelwood. /. chem. Soc., 1930,
3156-
201. S. Spiegelman and M. D. Kamen. Cold Spr. Harh. Symp.
quant. Biol., 12, 2\i (1947).
202. J.-I. ToMizAWA and S. Sunakawa. /. gen. Physiol., ^9, 553
(1956).
203. G. Gamow. Scient. Amer., ip^, 70 (1955) ; Proc. nat. Acad.
Sci.,Wash.,4T,y (i955)-
204. C. C. Lindegren. Nature, Lond., lyS, 1244 (1955)-
205. G. Gamow, A. Rich and M. Ycas. Advances in biological
arid medical Physics, 4, 2^ (1956)-
206. G. Gamow. Biol. Medd., Kbh., 22, no. 8 (1955).
207. A. N. Belozerskii. Vestnik Moskov. Univ., 2, 125 (1949)-
J. Brachet. Arch. Biol., Paris, 48, 529 (1937)-
208. N. S. Demyanovskaya and A. N. Belozerskii. Biokhimiya,
19, 688 (1954).
209. M. Grunberg-Manago, P. J. Ortiz and S. Ochoa. Science,
722,907 (1955).
210. (III. 71).
CHAPTER VII
THE DEVELOPMENT OF ORGANIC
MULTIMOLECULAR SYSTEMS :
THEIR ORGANISATION IN
SPACE AND IN TIME
Simple and complex coacervates.
It is characteristic of life that it is not scattered diffusely
through space but manifests itself in indi\idual,, very compli-
cated, multimolecular systems which are delimited from their
surroundings, that is, in organisms. In these there takes
place a continual succession of strictly ordered physical and
chemical processes based on interactions between the organ-
ism and its surroundings which, together, constitute its meta-
bolism.
From what has been said in the previous chapter we have
seen that it is wrong to suppose that the formation of such
highly-developed systems or organisms took place by the
combination of molecules of proteins, nucleic acids or other
substances which, if not actually endowed with life, w^re at
least fully capable of carrying out vital functions. The
development of the organisation peculiar to living things can
only have occurred as a result of evolution of systems which,
although more primitive, were nevertheless complete. At the
moment of their formation these systems did not have the
specific attributes of organisms. They were not alive and it
was not until later that they assumed these organisational
attributes and were transformed into systems which were
new in principle and of a higher order, that is to say, into
the first living things.
The organisation of any system must be considered both
in space and in time. On the one hand the system has a
certain size and structure, an ordered relationship between
its various parts. On the other hand processes are carried
301
302 ORGANISATION IN SPACE AND TIME
out within it in a co-ordinated and consequent way. The
comparatively simple and still lifeless systems which must
have been elaborated at some time from organic material in
the waters of the primaeval ocean, and which formed the
starting point on the way to the development of life, must
have undergone evolution leading to both the complica-
tion and perfection of their three-dimensional structure, and
also to improvements in their temporal co-ordination, giving
rise to the ordered harmony of the processes occurring within
them.
These two aspects of organisation are inseparable from
one another and it is only for convenience of exposition that
we shall sometimes discuss them separately in what follows.
As we have already seen, the purely abiogenic evolution of
organic substances on the surface of the Earth, in the waters
of the primaeval ocean, must have led to the formation of
very diverse substances which, in some cases, were of ex-
tremely high molecular weight, in particular protein-like
polypeptides and polynucleotides.
A characteristic feature of these substances, which include
individual proteins and even simple protein-like polypep-
tides, is the readiness with which they form complexes with
other organic substances of high molecular weight, among
them, with other proteins or polypeptides. Associations of
this sort between different protein-like substances give rise
to multimolecular formations with physical and chemical
properties which differ substantially from those of their
separate components. Furthermore, the protein-like polymers
arising out of these associations, like natural proteins, could,
under certain conditions, form multimolecular swarms which,
when they had reached a particular size, would separate out
from the solution into a new phase or collection of phases
which might be considered to possess a relatively simple
' morphology '. To this category belong, in the first place,
precipitates formed by the coagulation of colloids, gels and,
finally, materials aggregating in liquid form.
Quite a long time ago, at the turn of the century, many
workers (e.g.^) noticed that in solutions of hydrophilic colloids
there occurred another phenomenon as well as coagulation.
This was called ' demixing ' (Entmischung).^ The solution
SIMPLE AND COMPLEX COACER\ ATES 303
separates into two layers, one rich in colloidal substances and
another, clearly demarcated from it, which is almost free
from colloids.
For many years this phenomenon has been studied in
detail by H. G. Biuigenberg de Jong^ and his collaborators,
and recently also by many other scientists in various coun-
tries.* To distinguish it from ordinary coagulation, Bungen-
berg de Jong called this phenomenon ' coacervation '. The
colloid-rich liquid was referred to as a ' coacervate ' and the
colloid-poor liquid in equilibrium with it was referred to
as the ' equilibrium liquid '. In many cases the coacervate
does not separate out as a continuous layer but appears in
the form of very small droplets which are readily seen
under the microscope, floating in the equilibrium liquid. In
Bungenberg de Jong's experiments with protein coacervates^
the diameters of the droplets were between 2 and 670 p..
Moreover, it is not only proteins which form coacervates,
they may also be formed by other hydrophilic and even
hydrophobic colloids, both organic and inorganic.*^ For
example, they are formed by complex salts of cobalt,^ by
sodium silicate and ammonia,* by such organic substances as
polyvinyl derivatives, by solutions of acetylcellulose in chloro-
form or benzene,® and so forth.
The phenomenon of coacervation is particularly interest-
ing from our point of view in that, during the process of
evolution of organic substances, it must have been a powerfvil
means of concentrating compounds of high molecular w^eight,
in particular protein-like substances, dissolved in the hydro-
sphere.
It is well known that a coacervate may be obtained experi-
mentally from solutions of as little as o-ooi per cent of gelatin.
When this takes place there is a considerable increase in the
concentration of the protein in the droplets of coacervate,
which is particularly significant at very low concentrations.^"
For example, if a coacervate is formed from a 1 per cent
solution of gelatin, about 93 per cent of the gelatin is to be
foimd in the coacervate layer, but when the concentration
is lower the proportion of gelatin in the coacervate to that
in the equilibrium liquid is very much greater. It is hardly
possible to find any other equally effective means for con-
304 ORGANISATION IN SPACE AND TIME
centrating protein-like substances and others of high mole-
cular weight, especially at low temperatures. It is true that
a considerable concentration might also have been achieved
by the adsorption of substances of high molecular weight on
particles of clay, as was suggested by J. D. Bernal." This,
ho^vever, may lead to irreversible changes in the molecules
and, furthermore, they are firmly fixed to the surface of the
clay, while in coacervates the molecules of the compounds
of high molecular weight retain a considerable amount of
their independence and are concentrated without any par-
ticipation of inorganic precipitates being required.
On the other hand, if we take processes such as gel forma-
tion,^^ this can only occur in the case of gelatin, for example,
at concentrations of 1-5 to 2 per cent because gel formation,
in general, only fixes the relative positions of the molecules
and does not give rise to any concentration of them.
The importance of the formation of coacervates is not
confined to their action in concentrating organic compounds
of high molecular weight. Of no less importance is the fact
that coacervation leads to the formation of a disperse system
of coacervate drops with a highly developed surface separat-
ing it from the surrounding medium, and a definite internal
structure of the droplets. If coacervation merely led to the
formation of a continuous colloid-rich layer separated from
the rest of the solution, the possible part which it could play
in evolution would certainly be far more limited. It is
just because coacervation usually leads to the formation of a
large number of very small droplets with definite internal
structures that it appears to constitute an extremely important
stage in the spatial organisation of organic multimolecular
systems. •
On the basis of many years of work Bungenberg de Jong^^
has put forward the opinion that the process of coacervation
implies either a diminution in the hydration of the colloidal
particles, in their ability to retain a layer of water around
themselves, or else a diminution of that layer of water owing
to the activity of water-removing factors. The colloidal
particles do not, however, lose their surrounding water
entirely but retain those molecules of it which are firmly
SIMPLE AND COMPLEX COACERVATES 3O5
bound to them and are rigidly orientated relative to the
colloidal particles.
Thus, according to Bungenberg de Jong, coacervates form
a special class of colloidal sols in which the molecules of water
(or other solvent) are, to a certain extent, rigidly orientated
with regard to the particles of the colloid and in which,
therefore, a real boundary is formed between them and the
free molecules of the equilibrium solution.
However, in view of the extreme complication of the
phenomenon of coacervation, its theory cannot yet be held
to be fully worked out. In order to elucidate the nature of
the processes occurring we must turn to a study of some of
the simpler cases of coacervation. At present, solutions of
organic substances of high molecular weight are generally
regarded as thermodynamically stable molecular solutions
conforming to the phase rule.^* For practical purposes they
may be considered as ordinary liquids which contain very
large molecules. As early as 1904 G. Galeotti^^ showed that
the phase rule is applicable to protein solutions, and this was
later confirmed by H. Chick and C. J. Martin'' in 1910-13
and by other later workers. The same applicability was first
demonstrated for a number of other substances, including
gelatin, by V. Kargin and his collaborators.'^ If two simple
liquids of low molecular weight can be dissolved in one
another in all proportions (e.g. benzene and toluene or water
and acetone) then, naturally, there will be no layering out.
There exists, however, a large number of pairs of liquids
^vhich are only soluble in one another to a limited extent
(e.g. water and phenol or water and aniline). If we mix two
such liquids and shake up the mixture it will quickly separate
out into two layers, one of which might consist of a solution
of water in phenol and the other of a solution of phenol in
water. When this takes place, the difference between the
composition of the two layers at room temperature is very
great. As a result of this, the surface tension at the boundary
between the droplets formed by shaking and the surrounding
medium will also be very great and the droplets will coalesce
to form a continuous layer, thereby diminishing their surface
area and with it the surface energy. As the temperature rises,
the mutual solubility of the liquids increases, the difference
20
3o6 ORGANISATION IN SPACE AND TIME
in composition between the two layers decreases, the surface
tension of the droplets also decreases and, finally, at a particu-
lar temperature, known as the critical temperature of solubil-
ity, the boundary between the drops and the surrounding
medium disappears and a homogeneous solution is formed.
For systems of water and phenol this temperature is 65-9° C
and for mixtures of methanol and cyclohexane 491° C, etc.
When the temperature falls very slightly below this critical
temperature (only o-i -0-2° C), statistical variations in density
occur and the system begins once more to differentiate.
However, as the difference in composition between the
phases and the magnitude of the surface tension (some hun-
dredths of a dyne /cm. at these temperatures) are not so
marked as at room temperature, the droplets have no great
tendency to coalesce and they form a stable drop-coacervate
of a high degree of dispersion. When the temperature falls
further the droplets will once more coalesce and the two
substances dissolved in one another will separate out into
two layers. If we change the relative mutual solubility of the
two substances, for example by the addition of salt or
naphthalene, this correspondingly alters the temperature
relations of their mixtures or drop-coacervates.
Thus, in this simple example of two liquids of low mole-
cular weight which are partially soluble in one another,
the formation of drop-coacervates is limited to a narrow
region in which the surface tension is very low. If it in-
creases the liquids separate out completely ; if it approaches
too close to zero they mix completely.
In the systems with which we are concerned, containing
protein-like substances and others of high molecular weight,
the phenomenon must be more complicated and the ' play '
of surface tension will not, by itself, be enough to determine
the formation of drop-coacervates. Nevertheless, the essential
condition for coacervation, the limited mutual solubility of
substances, remains just as important as before.
Bungenberg de Jong obtained simple coacervates from
aqueous solutions of gelatin by adding dehydrating agents
such as ethanol or sodium sulphate, which decrease the
hydration of the particles of gelatin and thereby decrease
PROPERTIES OF COMPLEX COACERVATES 307
its solubility, so that the solution separates out into two layers
and forms a coacervate on warming to 50° C.
Simple coacervates may also be obtained from other pro-
teins such as amandin (a globulin foinid in almonds)'* by
dialysis in cold Avater, when the coacervate will dissolve again
on heating ; from alcoholic solutions of prolamines (cereal
proteins) by diluting them with water ; from alkaline solu-
tions of protamines by adding alcohol and so forth. In all
these cases the coacervate is formed under conditions in
which the solubility of the protein is diminished. These
simple coacervates, however, do not interest us nearly so
much as the complex coacervates w^hich are formed on mixing
solutions of t^vo or several colloids with different charges'^
such as gelatin and gum arable.
The structure and properties of
complex coacervate drops.
Bungenberg de Jong^" believes that w^hen such coacervates
are formed the electrostatic forces act in the opposite sense
to those of hydration. The effect of hydration tends to stabilise
the solution ^vhile the electrostatic forces are acting to draw
together the colloidal particles bearing opposite charges.
When the mutual attraction of the oppositely charged part-
icles reaches a certain intensity it can overcome the effect
of hydration and the particles combine to form a complex
coacervate. Thus such a coacervate is always under the
influence of two opposing forces, the electrostatic ones which
keep it together and those of hydration which tend to drive
the colloid back into solution.
One can, however, treat the formation of complex co-
acervates from the point of view w^hich has already been
discussed, as occurring under conditions of limited mutual
solubility of the components of the system. This approach
is particidarly applicable to such a coacervate as that of
gelatin and gum arable. The isoelectric point of gelatin is
at pH 4-82 but the coacervate can only exist at pH levels
between 1-23 and 4-82. Within these pH limits gelatin is
positively and gum arable negatively charged. Under these
conditions the charges can neutralise one another and the
solubility is thereby reduced. It is know^n that at the iso-
3o8 ORGANISATION IN SPACE AND TIME
electric point, at which pure proteins carry no net charge,
their solubiHty is at its lowest and therefore they are most
easily salted out with neutral salts. At pH 4-82 the net charge
of gelatin disappears and its hydration is least, but, on the
other hand, the charges on the gum arable particles are
not neutralised and the mean charge drawing together the
particles of gelatin and gum arable is greater than at lower
pH levels at which the charges can completely neutralise one
another. As the pH falls so the positive charge on the gelatin
increases and therefore requires more gum arable for its
neutralisation and for the formation of a coacervate. As the
pH increases, so the negative charge on the gum arable also
increases and it therefore requires the addition of a larger
amount of gelatin to form a coacervate. When the pH
becomes higher than the isoelectric point of gelatin and
both substances are negatively charged, their charges cannot
neutralise one another and coacervation cannot occur. In
all these cases the formation of a coacervate depends on the
mean net charge of the particles (i.e. on the algebraic sum
of the positive and negative charges of the associated part-
icles), and also on the degree of hydration and the solubility
of the particles. The same rules govern the formation of
coacervates from two proteins with markedly different iso-
electric points, and also from proteins and phosphorylated
starches and other such substances.
As the system becomes more complicated, when coacervates
are formed from three components, for example, the condi-
tions under which they can arise become more complicated
also, as the mutual solubility of substances does not merely
depend on their charges, but also on many other factors,
hydrogen bonds, the hydration of non-ionising polar gioups
(e.g. OH, CO, etc.), the interaction of hydrophobic groups,
etc. We have already indicated that the theory of coacerva-
tion is very complicated. This is because the mutual solubil-
ity of substances is itself very complicated and we have, as
yet, no complete theory of solubility. This, however, does
not fundamentally alter our approach to the phenomenon of
coacervation, which may be considered as the various mani-
festations of the limited mutual solubility of substances which
PROPERTIES OF COMPLEX COACERVATES gOQ
lead to the layering and separation of their solutions into
two liquid phases.
According to H. L. Booij and colleagues,"^ the stability
and the length of time for which coacervate drops can remain
unchanged does not only depend on the concentration of
H"*" and OH~ ions but also on the presence of other electro-
lytes.
The particular ratio bet^veen univalent and bivalent
cations is specially important. This is a manifestation of the
pronounced antagonism between cations which has been
studied in such detail in biological objects. Non-electrolytes
can have a stabilising effect on both simple and more com-
plicated coacervates by removing water from the colloidal
particles. For example, coacervate drops of gelatin and gum
arable may be kept in the equilibrium liquid for an indefinite
time in the presence of a solution of sucrose. ^^
A coacervate of gelatin and gum arabic is the classical
example on which Bungenberg de Jong did most of his work.
A number of later ^vorkers have also used such coacervates
for their experiments, among them D. G. Dervichian," who
confirmed the essential results of Bungenberg de Jong.
Gelatin can, however, form coacervates with other carbo-
hydrates as well as gum arabic, e.g. gum acacia,-* araban
and agar, and also with starches from various sources." As
the introduction of phosphoric acid into the molecule of
starch markedly increases its negative charge, phosphorylated
starches very readily form coacervates with gelatin.-® Gum
arabic also readily forms coacervates with other proteins.
Dervichian" obtained a coacervate which was stable between
pH 30 and pH 3-8 from gum arabic and haemoglobin. Gum
arabic forms two different coacervates Avith cltipeine, one of
which occurs at pH 5 and the other at pH 7.
We are specially interested in complex coacervates made
from two or several proteins. All that is necessary for these
to be formed is that, at some particular pH, their particles
shall bear charges of opposite signs. This is easily achieved
by mixing solutions of acidic and basic proteins. The greater
the difference between the isoelectric points of the proteins
used in the experiment, the more readily will they form
coacervates. For example, good coacervate drops can be made
giO ORGANISATION IN SPACE AND TIME
from mixtures of egg albumin with its isoelectric point at
about pH. 5 and clupeine with its isoelectric point at i2-i.
It has also been possible to incorporate enzymic proteins in
coacervates while retaining their catalytic properties. ^^
Fairly detailed studies have also been made of coacervates
containing nucleic acids, for example a coacervate containing
three components, gelatin, gum arabic and the sodium salt
of a yeast nucleic acid.^^ By means of studies using ultra-
violet light it has been possible to determine the absolute
amount of nucleic acid in a single drop of coacervate.^" It is
often found that a coacervate drop composed mainly of
gelatin and gum arabic has droplets within itself composed
of gelatin and nucleic acid (Fig. 27).
It is easy to form coacervates by the interaction of proteins
Avith phosphatides, sterols, glycerides and other lipids. In
particular, serious study has been given to protein-lipid
coacervates" composed of lecithin and various proteins
including casein, egg albumin, glycinin, clupeine, gelatin,
etc. Gelatin can also form coacervates with other lipids.
Bungenberg de Jong has recently paid special attention
to the coacervate formed from gelatin and potassium oleate,
because this coacervate has a very interesting structural
formation and fine bimolecidar boundary membranes. ^^
Potassium and sodium oleates can also form coacervates with
such proteins as egg albumin, serum albumin, various globu-
lins, etc. Dervichian also obtained protein-lipid coacervates
from haemoglobin and the albumin and pseudoglobulin of
blood with myristoylcholine.
Basing his opinion mainly on his own work ^vith gelatin,
Dervichian naturally arrived at the conclusion that the
phenomenon of coacervation is not, in itself, associated with
any chemical combination between the substances taking
part. But it certainly does not follo^v that combinations of
this kind cannot, in general, occur in coacervates. Thus, in
my own laboratory, stable compounds of protein and gum
arabic have been found to be present in the corresponding
coacervates.''^ G. A. Deborin and his colleagues^* obtained
compounds of egg albumin Avith ergosterol having properties
similar to those of natural lipoproteins. Doubtless nucleic
Fk;. 27. C:<)accr\ate with three coin-
pdiieius: ^ehiliii. ,u,iiin ardbie and
1 iliomicleic acid, x '520
(alter K\ veiiiox a).
COMPLEX COACER^ ATES AND PROTOPLASM 31I
acid and protein would also combine with one another to
some extent in coacervates of which they were components.''^
The occurrence of such combinations certainly adds con-
siderably to the complication of all the phenomena of
coacervation and would seem to favour the stabilisation of
the coacervates. Unfortunately this is still but poorly under-
stood.
As ^vell as the simple and complex coacervates, a third
group is often formed, the internally complex coacervates.
These formations arise when ions of opposite charges are
adsorbed on colloidal particles. A double layer of ions is
formed around the particles. When this happens, the degree
of ionisation depends on the chemical nature of both the
colloid and the adsorbed ions. Internally complex coacervates
may be obtained from solutions of proteins and carbo-
hydrates, sols of phosphatides and fatty acids, with the help
of various mineral salts. ^"^
Points of similarity between complex
coacervates and protoplasm.
The physico-chemical properties of complex and internally
complex coacervates (especially those having many com-
ponents) are very interesting from a biological point of view
as they are similar in many ways to those of protoplasm.
This resemblance has been stressed over and over again
by Bungenberg de Jong,^' though conflicting opinions have
been expressed in the scientific literature. For example, A.
Frey-Wissling'"* insists that protoplasm is based on solid
structural elements. He writes as follows: "Thus an
extremely fine network is formed, a molecular framework.
The meshes of this framework contain the interstitial sub-
stances: a solution of salts in water and lipids including
phosphatides." This point of view finds less and less support
and even Frey-Wissling himself admits that the structure in
question is very labile and can easily be disturbed, when the
cytoplasm turns into a typical liquid.^''
Indeed, as early as 1926 L. V. Heilbrunn" became firmly
convinced, on the basis of his extensive investigation of the
viscosity of protoplasm, not only that it has no visible struc-
312
ORGANISATION IN SPACE AND TIME
ture but that neither has it any invisible solid structure made
up of ' beams and braces '.
The further such studies proceed the clearer it becomes
that living, active protoplasm exists in the liquid state. It
is true that parts of it, both internal and external, may at a
certain period of life become rigid, when the phenomenon
described by Frey-Wissling is reversed.
Fig. 28. Protoplasm flowing out from the cut cells of
an alga.
However, it is not in these rigid formations that we should
look for the key to the structure of the substrate of life. In
most cases they play only a secondary part and the general
gelatinisation of protoplasm only occurs when the vital
processes are diminished, during anabiosis. The essential
organisation of active protoplasm is associated with the liquid
state.
What has been said applies equally to the cytoplasm and
the nucleus of the cell, and also to a number of formed
elements in the protoplasm, but especially to the mesoplasm
of plant cells. *^ Nevertheless, if the cell membrane is broken
and the mesoplasm flows out into the surrounding aqueous
medium (Fig. 28), it does not mix with the water but disperses
to form a multitude of sharply demarcated droplets which
look verv like droplets of artificial coacervates but have a
COMPLEX COACERVATES AND PROTOPLASM 313
number of the characteristics of intact protoplasm. This
phenomenon has been known ever since the time of Nageli*^
and has since been studied in detail by W. Kuhne,"*^ W.
Pfeffer/* L. V. Heilbrunn/^ W. W. Lepeschkin*'^ and many
others with numerous plant and animal materials. ^'^ It may
be observed by causing the plasmolysis of plant cells even
without breaking the cell membrane (Fig. 29). When this
Fig. 29. Domed plasmolysis of a cell of the
epidermal scale of an onion. Vacuole stained
with an anthocyanin (after Hefler).
occurs, the bulk of the protoplasm becomes separated from
the cell wall but is not dissolved in the water which has
passed through it. It remains in the form of a sharply
demarcated mass.** Similarly, as we have already seen,
although artificial coacervates are drops of liqtiid containing
50 to 85 per cent of water, they do not mix with their equi-
librium liquids, which are almost colloid-free.
We also find a close similarity between artificial coacervates
and protoplasm in regard to the phenomenon of vacuolisa-
tion. Under a number of conditions which cause a decrease
in the hydration of complex coacervates, clearly defined
vacuoles appear in them and these may take the form of
separate small bubbles or may coalesce to form a single
large vacuole. This phenomenon may be observed under
the action of chemical agents and also on changing the
temperature, under the influence of electric ctuTcnts and
so forth. When the agent which brought about the vaciio-
lisation is remo\'ed the phenomenon is reversed and the
coacervate rettirns to its original state. In a similar way
the same physical and chemical agencies can induce vacuolisa-
314 ORGANISATION IN SPACE AND TIME
tion in the protoplasm of very diverse animal and vegetable
objects.*^ It is interesting that this vacuolisation occurs not
only in the cytoplasm, but also in the nucleus, nucleolus,
chondriosomes and other organelles of the cell. This has led
a nimiber of authors to state that these organelles are of the
nature of coacervates/"
The great similarity between artificial coacervates and
protoplasm has been revealed by concurrent studies of such
properties as their viscosity, their behaviour with neutral
salts, changes of pH and temperature, their behaviour in an
electric field and so forth. In introducing an extensive
account of his findings concerning the problem A. S.
Troshin'^^ writes as follows:
Thus a number of features which are characteristic of the
physico-chemical properties of coacervates seem also to be char-
acteristic of protoplasm. The view of many investigators, that
the protoplasm of living cells consists of a system of complex
coacervates, is thus fully confirmed by experiment.
The following two characteristic properties of complex
coacervates are specially important in relation to the argu-
ment which follows: (1) their tendency to form structures ;
(2) their ability to adsorb selectively substances from the
surrounding equilibrium liquid. It has been indicated above
that on the coacervation of organic substances of high mole-
cular weight there is formed a disperse system of coacervate
drops with highly developed surfaces and definite internal
structures. If the stability of the drops of coacervates of
simple liquids is determined by the surface tension of the
boundary layer then that of coacervates of proteins and other
substances of high molecular weight is determined by far
more complicated circumstances. In this case too the surface
tension (which amounts to 0-2-2 dyne /cm. for coacervates)
will naturally play some part, but will not be decisive. The
work of P. Rebinder and his schooP^ has shown that the
stability of disperse systems resembling emulsions depends to
a considerable extent on the stabilising effect of the adsorbed
layers at the surface which separates the droplet from the
continuous phase. This stabilising effect is especially marked
when the adsorbed layer with its associated solvent has a
COMPLEX COACERVATES AND PROTOPLASM 315
rather high degree of structural viscosity or, when the solu-
tion is highly saturated, even elasticity and mechanical
resistance to deformation ; in the presence of such rigid
layers the stability of disperse systems may be extremely
great.
It is very significant that proteins themselves should
be among those substances which give rise to differentiated
surface layers. The transformation of protein molecules in
the surface layers into a laminar state with an increase in
their mechanical rigidity is well known ; it has been studied
in detail, particularly by A. Trapeznikov. However, although
in coacervates of simple liquids the elastic surface layers
can only arise by the admixture of a third substance, in
coacervates of proteins they can arise directly from parts of
the protein molecules themselves or other substances associ-
ated with them such as lipids, polysaccharides, etc., which
migrate to the boundary layer and form molecular layers at the
interface, or perhaps only a single layer with changed struc-
tural and mechanical properties. This seems to be just the
sort of phenomenon which lies at the basis of the formation
by protein coacervates and protoplasm (after disintegration
of the cell with water) of sharply defined surface films with
fairly rigid mechanical properties. This has nothing to do
with surface tension or with the fact that the protoplasm
forms a separate phase, but is due to the transformation
of the protein molecules and their associated groups in the
surface layer into a different structural state.
At the interfaces between the drops of a complex coacervate
and its equilibrium liquid, or between a vacuole and the
coacervate in which it lies or, finally, between the drops of
one coacervate and another in which it is included, one
may certainly demonstrate the presence of colloidal films
made up of oriented colloidal particles of whichever com-
ponent is present to excess in the coacervate-equilibrium
liquid system. Such films are formed especially readily in
protein-lipid coacervates. In particular, Bungenberg de
Jong" and his colleagues have recently studied coacervates
of gelatin and potassium oleate and concluded that they
contain micellar films in the form of a sandwich, molecules
3l6 ORGANISATION IN SPACE AND TIME
of oleic acid being arranged in a regular order between two
unimolecular layers of protein
The films have definite structures and permeabilities which
depend on their chemical composition and electric charge.
For example, if the boundary film of the coacervate is nega-
tively charged and the surrounding liquid contains calcium
ions, the film is strengthened (forming an internally complex
coacervate with the adsorption of calcium ions). Potassium,
on the other hand, weakens the film. Thus calcium and
potassium act as antagonists in the coacervate. The proto-
plasmic films dividing the nucleus from the cytoplasm and
the nucleolus from the karyoplasm are similar in nature.
Many authors claim to have found such films around the
chondriosomes, karyosomes, chromosomes and other organ-
elles and inclusions in cells.
The drops of protein coacervates also have an internal
structure which distinguishes them fundamentally from
simple drops of liquid. This structure manifests itself chiefly
as a rather labile state of orientation of the particles of
the coacervate. As we have already mentioned, complex
coacervates in the aggregated state take the form of more
or less freely flowing liquids, but under some circumstances
orienting forces may develop within the coacervates so that
they cease to behave like ideal liquids. These forces cause
the particles of the coacervates to assume a definite orienta-
tion with regard to one another. This may, for example, lead
to the anisotropy of some coacervates,^* although, at first,
they remain of a liquid consistency and their capacity for
double-refraction is very labile.
According to Bungenberg de Jong,^^ the colloidal particles
in complex coacervates are not, as a rule, oriented in a
definite way, because in such coacervates there is no cohesion
between the particles. But if, by some means, the positive
or negative charge on the micelles of the coacervate is
increased or their hydration is decreased, then the micelles
approach one another and become oriented in a definite
mutual relationship. The so-called * oriented coacervates '
which are thus obtained show many signs of having a struc-
ture. For example, if the particles of which it is composed
are rod-shaped, the drops of the coacervate will be ellipsoidal.
COMPLEX COACER VAXES AND PROTOPLASM 317
In oriented coacervates one may also detect the formation
of ' micellar crystals ', fibrils and fibrillar structures. Bungen-
berg de Jong and his colleagues^ "^ observed the formation and
disappearance of these structures in coacervates of various
proteins, lecithin, nucleic acid, polymeric carbohydrates, etc.
VACUOLE
INCLUSION
FAT DROPLETS
VACUOLE
Fig. 30. Model of a cell
(after Bungenberg de Jong).
1, II and III indicate individual coacervates.
The so-called mtdtiple complex coacervates," made up of
several different components, are of great interest. The
coacervate which we have already discussed, made up of
gelatin, gum arable and sodium nucleate, may serve as an
example of this class. It may exist as a single complex
coacervate or may form two different coacervates which do
not mingle ; the drops of one coacervate may contain small
droplets of the other.
The presence of double coacervates of this sort may readily
be demonstrated by staining. For example, the coacervate
of gelatin and nucleic acid which lies within the coacervate
of gelatin and gum arable is selectively stained by methylene
green. Bungenberg de Jong, along with many cytologists and
physiologists, considers that the living cell is, essentially, a
very complicated multiple coacervate^* (Fig. 30).
From this point of view the nucleus may be regarded as
a coacervate lying within another coacervate, the cytoplasm ;
3l8 ORGANISATION IN SPACE AND TIME
and the nucleolus as a further coacervate included within
the nucleus. Guilliermond says that the development of the
chondriosomes and their later transformation suggests that
they also are coacervates. According to I. N. Sveshnikova^^
the same may be said of microsomes. Finally, according to
P. Makarov, the formation of chromosomes in the resting
cell before division suggests that they are coacervate-like in
nature.
The process of development of vital-staining granules in
protoplasm may serve as an example of the formation of
droplets of one coacervate within the substance of another.*"
A. S. Troshin considers that the formation of granules of
secretion within glandular cells is generally similar in
mechanism to the formation of multiple coacervates.
As we have already mentioned, the process of coacervation
leads to the formation of a boundary or surface separating
the coacervate from the equilibrium liquid. This is associ-
ated with the appearance of new surface phenomena and,
in particular, with the adsorption by the coacervate of various
substances present in the surrounding medium.
Many organic substances are extracted almost completely
by coacervates from their equilibrium liquids. Even when
the concentration is as low as oooi per cent a coacervate may
sorb some substances from the water in which they are
dissolved. Some of the molecules which are sorbed by the
coacervate pass into its liquid by hydration and some become
associated with the colloidal particles themselves, sometimes
entering into chemical combination with them so that quite
substantial chemical alterations in the composition of the
coacervate may take place.
The selective character of the sorption is very important.
Coacervates may accumulate large amounts of one substance,
collecting it from dilute solutions, while on the other hand
they may take up only very limited amounts of another,
although this is present in high concentration in the equi-
librium liquid. This peculiarity arises from the facts that,
on the one hand, the colloidal particles of the coacervate
themselves adsorb some particular substances specifically
while, on the other hand, the solubility of substances in the
COMPLEX COACERVATES AND PROTOPLASM 9,IC)
water of hydration of the coacervate drops is different from
their solubility in ordinary water.
A number of workers (D. Sabinin,®^ D. Nasonov,®^ A. S.
Troshin*^^ and others) who oppose the membrane theory of
the permeability of the cell, believe that its ability to take
in this or that substance from the surrounding medium and
to discharge it again is a manifestation of the sorptive powers
of protoplasm, which can only be understood on the assump-
tion that protoplasm is a coacervate system. These authors,
therefore, attach very great significance to the study of the
mechanism of distribution of substances between a coacervate
and its equilibrium liquid in the attempt to work out the
theory of the uptake of substances by the living cell.
The multifarious organic compounds of high molecular
weight which first arose in the waters of the primaeval ocean,
various polymeric carbohydrates, amino acids, nucleotides
and so forth, cannot have been fundamentally different in
their colloid-chemical properties from the polymeric com-
pounds with which we are familiar.
In solutions of them, as in the solutions, to which we are
well accustomed, of proteins, polysaccharides or polynucleo-
tides, there must have been a pronounced tendency to the
formation of intermolecular associations. Complex coacervates
must have been formed with great readiness. As we have
seen above, the essential condition for this is the simultaneous
presence in a solution of two or several organic substances of
high molecular weight with different charges. The great
complexity and diversity of the chemical transformations
which took place in the primaeval hydrosphere must, in
themselves, have guaranteed that this condition would be
fulfilled. Therefore, sooner or later, at some point or another
in the primaeval ocean, there must necessarily have come into
existence collections of molecules of organic polymers and
their separation in particular places from the surrounding
medium to form drops of complex coacervates.
This must have been largely facilitated by the relatively
very high concentrations of organic substances in the primi-
tive * terrestrial soup ' to which we have already drawn
attention. The formation of complex coacervates could, how-
ever, have occurred even when the concentration of organic
320 ORGANISATION IN SPACE AND TIME
polymers was far lower. Under experimental conditions it
takes place in solutions containing only a few parts per
million of these substances.
The water of the seas and oceans as we know them now
only contains negligible traces of organic compounds, which
arise secondarily from the decay of dead organisms. In the
vast majority of cases these substances are quickly consumed
by the organisms of the plankton, for which they provide
nourishment. Sometimes, but comparatively seldom, they
may remain in the depths of the sea for a relatively long
time untouched by micro-organisms. Numerous studies of
the slimy bed of the ocean at great depths indicate that,
under these conditions, dissolved substances of high molecu-
lar weight do, in fact, form aggregates similar to coacervates.
While studying the waters of the seas and oceans at depths
of hundreds and thousands of metres, A. Kriss and his col-
leagues** found submicroscopic formations reminiscent of
coacervates which they were able to photograph with an
electron microscope. The nature of these formations is still
not clear but nevertheless Kriss's observations are of great
interest.
Thus, all the evidence now available agrees in indicating
that the organic polymers which were originally formed, and
in particular the protein-like polypeptides of high molecular
weight, must, at some stage in the evolution of carbon com-
pounds, have separated out from a homogeneous solution
in the form of multimolecular aggregates similar to the drops
of coacervate which are obtained under laboratory conditions.
The formation of coacervates in the waters of the hydro-
sphere was a very important stage in the evolution of the
primary organic substances and in the process of development
of life. Until this occurred an organic substance -was inextric-
ably merged with its surrounding medium, uniformly dis-
tributed throughout the whole extent of the solvent. When
coacervates were formed, the molecules of organic polymers
became concentrated at particular points and separated from
the surrounding medium by a more or less sharp boundary.
Thus there were formed entire multimolecular systems, co-
acervate drops, each of which already had a certain individual-
ity in contrast to all the rest of the external world surrounding
STATIONARY OPEN SYSTEMS ^21
it. In addition, each such drop had a certain structure
peculiar to itself alone. Previously, in the solution, there
^vere only irregularly moving particles of organic substance,
all the properties of which were determined simply by their
intramolecular structure. In the drops of coacervates these
particles were arranged in a definite relationship to one
another, giving rise to a certain spatial organisation and
there were superimposed on the earlier organic-chemical
relationships new colloid-chemical laws which were derived
from the interaction of substances of high molecular weight
in a multicomponent system.
The primary formation of these coacervate drops is worthy
of special attention because the material basis of life at the
present day, protoplasm, has a similar structure and, from
a purely colloid-chemical point of view, it would seem, as
we have shown above, to be a multiple complex coacervate.
From this one must not, of course, draw the reverse conclu-
sion that the original coacervate drops, or any which have
been produced artificially, are in any way living. The differ-
ence is not merely due to the extreme complexity and the
far-reaching spatial organisation of protoplasm compared
with the great simplicity and lability of coacervate drops.
The actual stability of these two systems, their capacity to
exist for a long time, is based on completely different prin-
ciples.
Stationary open systems.
An artificially produced coacervate, or a drop which arose
naturally by separating out from organic solution in the
waters of the ocean, is in itself a static system. The longer
or shorter duration of its existence, which is associated
with maintaining the constancy of the properties of the
system in time, depends on its being in a thermodynami-
cally stable or metastable state. The more stable a coacervate
drop, regarded from a purely colloidal point of view, the less
likely it will be to disappear as an individual formation after
any given lapse of time by amalgamating with other drops
or by dissipating itself into the surrounding solution. Unlike
this, the coacervate structure peculiar to living protoplasm
21
322 ORGANISATION IN SPACE AND TIME
can only exist so long as it carries out an unending succession
of multitudinous biochemical processes at a great speed,
which together make up its metabolism. Thus it is only
necessary for these processes to be suspended or radically
changed for the protoplasmic system itself to be destroyed.
Its continued existence, the maintenance of its form, is
associated not with immutability or rest but with continual
motion. Thus protoplasm is not a static but a ' stationary ' or
flowing system.
This characteristic property of living things was already
recognised among the ancient Greeks by the great dialec-
tician Heraclitus^^ who taught that our bodies flow like
streams ; the material in them is renewed like water in a
river. In fact a river or a simple stream of water flowing
from a tap enables us to understand, in their simplest form,
a number of essential features of the organisation of irrevers-
ible or open systems, of which living protoplasm is a particu-
lar example. If the tap is not fully open and the pressure
in the water system remains constant, the stream of water
issuing from the tap will stay almost the same shape, as
though it had been congealed. We know, however, that this
shape is nothing but the visible manifestation of an unending
flow of particles of water which continually enter and leave
the system at a particular rate. The very existence of such
a system depends on the fact that a constant succession of
new molecules of water is passing through it at a steady rate
the whole time. If the flow is interrupted the stream ceases
to exist as such.
In an analogous way the organisation of protoplasm is
based on a stationary state by virtue of the fact that the living
organism is constantly exchanging material and energy with
the medium which surrounds it ; that within it a series of
irreversible co-ordinated reactions are being carried out at a
definite rate, as a result of which substances which enter the
organism from the outside medium undergo a series of trans-
formations within it and the products of their decomposition
are again liberated into the outside medium.
THERMODYNAMICS AND KINETICS 323
The thermodynamics and
kinetics of open systems.
The mechanistic view of the organisation of living bodies
which prevailed among biologists until recently, namely that
they were like machines made up of immutable steel com-
ponents, made such a concept of organisms as open systems
very difficult to accept. However, the use of marked atoms
in biochemical and physiological investigations^® has shown
beyond doubt that almost all the substances of the living
body, its proteins, nucleic acids, lipids, etc., are completely
renewed in the course of a short space of time ; that the
material substrate of life is constantly being exchanged with
the surrounding medium, it is continually being broken
down and synthesised again fi'om substances derived from
the external world. This provided a complete vindication
of Michurin's principle of the unity of the organism and the
environment ; the contention that a living thing cannot
be considered in isolation from its environment, without
reference to this unity.®'^
On the other hand, the contemporary wide adoption in
industrial practice of technological methods based on con-
tinuous irreversible processes has led many physicists and
chemists to undertake a complete revision of the theory of
open systems, which has introduced many new concepts into
the classical thermodynamic and kinetic theories, which are
mainly based on the kinetics and equilibrium of reactions
in completely isolated systems.
In his very interesting book. An introduction to the
thermodynamics of irreversible processes, I. Prigogine®*
divides all limited systems into three fundamental classes :
(i) open, (2) closed and (3) isolated systems. The first group
comprises systems in which there is a constant exchange of
both matter and energy between them and their surround-
ings. In closed systems the exchange is only of energy, the
exchange of matter being absent. Finally, the third group
comprises systems which are completely isolated from their
surroundings and do not exchange either matter or energy
with them. The latter two groups may be combined under
the general term ' enclosed systems ' to distinguish them
324 ORGANISATION IN SPACE AND TIME
from the group of open systems, to which living organisms
belong.
In enclosed systems the only things which can react
chemically with one another are substances which are present
in the system. The constancy of the properties of the system
over a period is characterised by a state of equilibrium in
which the rate of a reaction in one direction is the same as
the rate of the same reaction in the opposite direction. The
thermodynamic criterion for this equilibrium is the presence
of the minimal amount of free energy and the maximal
amount of entropy in the system (in other words the attain-
ment of the most probable state of the system). Processes
occurring spontaneously within an enclosed system cannot
cause it to reach a less probable state, that is to say, they can
only maintain the entropy at its existing level or increase
it, according to whether the processes in question are revers-
ible or irreversible. So long as the entropy of a system is
increasing, equilibrium has not been reached and, conversely,
when equilibrium is set up, the rate of increase of entropy
falls to zero.
In contrast to this, in open systems there is a continual
accession of substances from the external medium into the
system (from which it is separated in some way) and also a
discharge of chemical substances, which arise within the
system, back into the external medium. The constancy in
time of the properties of such an open system is, therefore,
not characterised by thermodynamic equilibrium (as is the
case in enclosed systems) but by the setting up of a stable
condition, the constancy of which is maintained by the rate
at which chemical reactions proceed in one direction and
bv the diffusion of substances within the system.
Stationary processes may, of course, occur in closed systems
though not in isolated ones,"^ for example, the transfer of
heat. The stationary state in which we are interested is that
involving chemical reactions and this is peculiar to open
systems. We shall therefore direct our attention to these.
Thermodynamic equilibrium and the stationary state
resemble one another in that, in both cases, the constancy
of the properties of the system is maintained. The essential
difference between them is that in thermodynamic equi-
THERMODYNAMICS AND KINETICS
325
librium there is, as a rule, no change m free energy, whereas
in the stationary state the free energy enters and leaves the
system at the same constant rate.
Thus, the stationary state is kept constant, not because the
free energy is minimal (as is the case in thermodynamic
equilibrium) but because the system is continually receiving
free energy from outside in amounts which compensate for
its decrease within the system ; it is ' fed ' with free energy
at the expense of the environment.
iL
f^K>
—
— t
B
II — '
'^
. n
Pi.
K rwOORAPH
WATER MODEL OF
A STEADY STATE SYSTEM
Fig. 31. Water model of the Fig. 32. Records made with the water
simplest steady state system. model of a steady state system.
A. Change of k to new level with
k <k . B. Same with k > k . C.
o z o z
Single and repetitive brief changes of
k with A- <:k . D. Same with k > k .
o z o z
Reproduced by permission from originals of Figs. 8 and
9, Alan C. Burton, /. cell. comp. Physiol., /./, 344.
Similarly the entropy of a closed system in equilibrium is
at a maximum, whereas, in an open system in the stationary
state, it is kept constant but not maximal. The chemical
thermodynamic theory of irreversible processes occurring in
open systems has so far only covered small deviations from
thermodynamic equilibrium. From the results of H. Eyring
and others^" it would seem that it is only applicable where
Az = about 02 kcal/mole. However, within these limits
thermodynamics has established that, in general, there are
linear relationships between the changes in properties of the
system (e.g. chemical transformations or the diffusion of
substances) and the strength of the forces acting on it (the
giadients of free energy, concentration, temperature, etc.) for
a number of simultaneous processes.
326 ORGANISATION IN SPACE AND TIME
The kinetics of processes occurring within open systems
are very complicated and pecuHar to them. We shall try to
explain the kinetic peculiarities of the chemical reactions in
open systems by analogy with the simplest hydrodynamic
model of stationary systems. A vessel with a liquid flowing
through it may serve as such a model.'' This is represented
diagrammatically in Fig. 3 1 .
The vessel S in which the liquid stands at a constant level
represents the source of substances entering the system (the
external medium). The vessel Z is a sink (this also represents
the external medium into which the system discharges the
products of the reactions which have occurred within it).
The open system itself is represented by the vessels A and B
which are connected with the ' external medium ' by means
of the taps Ko and Kz which represent the diffusion constants
of substances into and out of the system. The stationary state
of the system is attained when the water is at particular
levels in vessels A and B, which correspond to stationary
concentrations of the substances taking part in reactions in
the chemical open system. Tap K regulates the flow of water
from A to B and represents a constant rate of the reaction
with which we are concerned, A -^ B. There is also shown
a kymograph which records, by means of a float, the level
of the water in vessel B.
When the flow of water through the system has been
established, this level will remain constant like the static
level of water in an ordinary bucket. In our system, however,
there is a continual dissipation of energy due to the flow
of the water. This is what maintains a constant level in
vessel B.
To make it easier to follow the analogy between the hydro-
dynamic model and the chemical reaction in an open system
we may give the following diagram
! I
I I
Ko I Ky I Kz
S — > A ^i^ B — > Z
I K, I
I I
THERMODYNAMICS AND KINETICS 327
Here the dotted lines represent the boundaries of the open
system, such as the cell wall or the surface film of a coacervate
drop. S and Z represent the external medium, Ko and Kz
the velocity constants for diffusion or penetration of the
membrane, K^ and K^ the velocity constants for the chemical
reaction A^=^B taking place within the open system. In
the hydrodynamic model if we alter the setting of the taps
Ko and Kz (which would be the equivalent of changing the
rate of diffusion in the chemical analogy) or turn tap K
(which corresponds to a change in the rate of reaction), then
a new level will be established in vessel B, i.e. a new station-
ary state will be set up. Thus it is possible to establish an
infinite number of stationary states in an open system,
depending, particularly, on changes in the rate of the reaction
which is occurring within the system.
It is well known from the classical kinetics of closed systems
that the introduction of a catalyst into a system will alter
the speed with which it reaches equilibrium, but does not
affect the position of the equilibrium because the magnitudes
Ky and K2 are changed in such a way that the ratio between
K
them remains constant {K =-~). Two ordinary vessels con-
taining water at different levels and connected with one
another by a tap may serve as a hydrodynamic model of such
a closed system. The amount which this tap is open will
affect the rate at which the fluid level becomes the same in
both buckets but will not affect its position.
In open systems, on the other hand, the introduction of a
catalyst will, as we have already seen, change not only the
rate of the reaction but also the position of the ' equilibrium '
(the stationary concentrations of the components of the
system) as may be shown by purely mathematical means. A
very characteristic feature of the establishment of a new
stationary state in open systems is that it does not come about
directly but through extreme states (through a maximum or
minimum).
Thus, at the beginning it deviates more sharply from the
original state and later approaches it again more closely
(though not completely) as is shown on the accompanying
328 ORGANISATION IN SPACE AND TIME
curve obtained by Burton with a hydrodynamic model
(Fig. 32).
K. G. Denbigh and his colleagues^^ gave analogous curves
for the chemical reaction of the oxidation of glucose. We
must also draw attention to yet another curve obtained by
KIO3
in ml.
■o — o-
"W^-^^
JQ.
-i_
30 50 70 90 no 150 150 170
TIME IN MINS.
Fig. 33. Changes in the stationary state during the
enzymic oxidation of ascorbic acid (after Pasynskii
and Blokhina). Explanation in text.
A. Pasynskii and V. Blokhina^^ for the reaction of enzymic
oxidation of ascorbic acid occurring under the conditions of
an open system. The experiment was conducted as follows :
a solution of 12 per cent of ascorbic acid and 02 per cent
of hydrogen peroxide was passed through a small cylinder
covered at one end by a cellophane membrane. The other
side of the membrane was washed with a stream of distilled
water. In the diagram (Fig. 33) the ordinate shows the titre
of ascorbic acid in the mixture and the abscissa the time
in minutes.
When the stationary state had been established (A B), a
solution of peroxidase was introduced into the cylinder at
the point B, and its titre fell to level C. Owing to the associa-
tion of the decrease in the concentration of ascorbic acid
with a decrease in the rate of its diffusion through the mem-
brane, however, after reaching a minimum BCD, a new
stationary state was established at level DE. This experiment
THERMODYNAMICS AND KINETICS ^29
may serve as an example of the course of an enzymic reaction
showing the characteristic features of reactions in open
systems: a change in the stationary state, the dynamic
stabilisation inherent in the system, and the transition from
one stationary state to another through an extreme state
(through a minimum). Thus, for every open system there
must be an unlimited number of stationary states in which
any change, even of only one of the parameters of the system,
will, in principle, necessarily lead to the establishment of a
new stationary state.
If several reactions are taking place within the system
instead of only one, and if these follow one another in a
longer or shorter chain of transformations or are, in general,
associated with one another in time, then the equation for
stationary concentrations in open systems becomes far more
complicated. For direct, unbranched, chains of reactions, for
example, it may be represented as follows :
Kq\ Ki Ki K3 K4 ^n—1 '-^z
S > A ^ B ^ C , . D ,^ — ,^ N > Z
The chains of chemical reactions taking place within open
systems may, however, branch, e.g. :
S->A^B^C^D^ ^ N -> z
1L t ••
X ^ ^ Y
This may lead to the formation of a complicated network
of reactions with many branches and internal cycles. It may
be compared, in some respects, to a railway network on which
a large number of trains are moving in various directions at
various speeds. On the basis of his own profound kinetic
analysis of these phenomena C. N. Hinshelwood^* concluded
that in networks of chemical reactions of this sort the limiting
states are not always determined by the slowest individual
reaction forming a separate link of the chain but depend
on the relationships of a whole series of reaction-velocity
constants. In fact, in a complicated network of reactions,
the transition between two chemical states may occur, not
330 ORGANISATION IN SPACE AND TIME
by one, but by several pathways, just as the quickest way of
getting from one place to another over a railway system with
many branches and loops may involve the use of different
routes comprising combinations of different sections of rail-
way line. In chemical kinetics, when alternative routes of
this sort are available, special importance naturally attaches
to the route along which the reaction can proceed at the
greatest speed under the given conditions. But we must
not forget that (as all motorists know) the shortest way is not
always the fastest, and it is often better to follow a circuitous
route which runs over a well-made highway. Similarly in a
complicated network of chemical reactions it often happens
that a process of transformation comprising a large number
of separate links is carried out very quickly to achieve a
chemical transformation which is based on but one, or a few,
chemical acts.
Thus, in a complicated network of chemical reactions the
attainment of the highest speed for a process involves not
merely the speeding up of one of its stages, but the establish-
ment of the most effective relationship between all the para-
meters of the process. In addition, any alteration in the
external conditions acting on the process, by speeding up
or slowing down any one stage of the chemical transforma-
tion, will lead to a rearrangement of the kinetic parameters
of the system as a whole.
The establishment of such a network connecting the
kinetic parameters under the influence of a change in the
external conditions does not, according to A. C. R. Dean and
C. N. Hinshelwood," take place instantaneously but requires
a certain time for reconstruction. In its establishment the
attainment of the best rate for the process is sometimes even
hindered for a period to allow the working of less effective
alternative processes which, however, are already in action.
All these processes can not only be worked out theoretically,
but can also be demonstrated experimentally, especially by
analogy with a hydrostatic model in which there are
several stationary systems having common original and final
reservoirs.
We may summarise all that has been said about the
thermodynamics and kinetics of open systems by stating the
THERMODYNAMICS AND KINETICS .S3'
following essential characteristics of these systems in a form
borrowed from the review of Pasynsk.ii/®
1. The stationary state of open systems is characterised by
a constant minimum rate of dissipation of free energy
and a constant minimum rate of development of entropy
within the system in contradiction to the state of thermo-
dynamic equilibrium in closed systems in which these
functions have a value of zero.
2. In open systems there can occur processes leading to a
decrease in entropy owing to their thermodynamic associa-
with processes leading to an increase in entropy in the
external medium.
3. In open systems there can exist an infinite number of
stationary states depending on the internal parameters
of the system (the original concentration of the com-
ponents, the diffusion constants, the rates of the reactions
and so forth), and on the external conditions (tempera-
ture, pressure and so forth). A change in any of the
conditions of a stationary state leads to a rearrangement
of the kinetic and diffusion parameters of the system and
to the establishment of a new stationary state.
4. In open systems where alternative routes are available
the directions of chemical changes are determined by the
principle of the maximal reaction velocity.
5. In an open system the presence of catalysts affects not
only the rate of the reaction, but also the stationary
concentrations of the reagents.
6. When the conditions are altered in the stationary state
in open systems, processes occur which tend to conserve
the properties of the system (the dynamic stabilisation
of the stationary state).
7. The transition from one stationary state to another in
an open system where the reaction velocities are not very
great does not proceed according to a smooth curve but
usually passes through an extreme state (through a maxi-
mtim or minimum).
It is very significant in connection with our problem that
the principle according to which protoplasm is organised
in time is similar to the principle of organisation of open
332 ORGANISATION IN SPACE AND TIME
systems. An organism or any one of its cells can only exist
so long as there passes through it a continual flow of fresh
particles of matter with their associated energy, from the
external medium and back into it.
When an organism receives from the external medium
compounds which are foreign to it, a whole series of co-
ordinated reactions transmute these compounds into the
substances of its own body. This is the ascending branch of
metabolism (assimilation). However, assimilation is intim-
ately connected in the organism with the converse process,
dissimilation, the decomposition of compounds which form
part of the body, the formation of the end products of this
decomposition and their discharge into the external medium.
From a purely chemical standpoint assimilation and
dissimilation, the whole of metabolism, is a complicated
association of an enormous number of extremely simple and
relatively uniform reactions. These are well known to chemists
and easily carried out outside the living organism under
laboratory conditions ; they include oxidation, reduction,
hydrolysis, phosphorolysis, aldol condensation, the transfer
of methyl groups, etc. There is nothing specific to life about
any one of these reactions. What is specific about the organ-
isation of biological metabolism seems to be that in proto-
plasm the reactions are strictly co-ordinated and harmonious,
that they follow one another in a definite regular order and
not at random, forming long series, branching chains and
closed cycles of chemical reactions, just as we have described
above with reference to the networks of reactions occurring
within open systems."
Thus the simplest abiogenic system which could have
served as the starting point for the evolutionary process which
led up to the appearance of life must already have had the
organisational features characteristic of open systems, in
which the separate reactions form a network of chemical
transformations which are co-ordinated in time.
How could such an original system have arisen? How
could there have arisen at definite points in the primaeval
ocean, out of the diverse interlacing reactions, some of that
order, that regularly functioning network of reactions which
is peculiar to open systems?
THERMODYNAMICS AND KINETICS 333
As we have shown above, at a particular stage in the history
of the Earth, diverse organic substances were formed and
reacted chemically with one another in many different ways.
The participation of free radicals, which were formed as a
result of the effects of ultraviolet radiations, electric discharges
and radioactive radiations, still further increased the number
of possible reactions. Over a long period it is probable that
almost all the possible chemical reactions between the sub-
stances present actually took place to a greater or less extent.
However, in the general disorderly association of all con-
ceivable chemical reactions of those times, a single chemical
reaction probably predominated at any particular place and
others in other places. This was essentially due to the fact
that the transformation of any substance entering into a
reaction preferentially followed the chemical course which
assured the greatest speed of reaction under the given circum-
stances.
According to the theory of chemical kinetics, if the differ-
ence in free energy, Af, is the same for all the reactions,
the transformation of the bulk of a given substance will
follow the course of reaction along which it can proceed most
quickly. The attainment of the greatest speed for a given
reaction depends, in its turn, both on the chemical nature
of the reacting substances and on the local conditions of the
medium, temperature, pressure, and particularly the pres-
ence of appropriate catalysts, especially when such a catalyst
specifically accelerates only one of all the possible reactions.
This may be illustrated by the following elementary
scheme. Let us suppose that we have any organic substance
A, which can be transformed into substances B, C, D, etc.
In our scheme the rates of these reactions are represented by
the vectors, the length of ^vhich indicates the rate of any
reaction.
C
D ^ A > B
In this diagram we see that the rate of the reaction A -> B is
seven times that of the reaction A -^ D which, in its turn.
334 ORGANISATION IN SPACE AND TIME
is only half that of the reaction A -> C. Naturally, after a
certain time, when all of substance A has disappeared, the
resulting mixture will be found to contain 70 per cent B,
20 per cent C and 10 per cent D. Thus, under the given
conditions the bulk of substance A will have been converted
to substance B, that is to say, it will have followed the path
along which the reaction proceeds fastest.
If we apply to such a system any influence which will
increase the rates of all possible reactions equally (e.g., raising
the temperature) then the ratio of the end products will
not be changed in any way. If, however, we add to the
original mixture a catalyst which specifically increases, by
perhaps a million times, the rate of the reaction A -> D alone
and does not alter the rates of the reactions A ^ B and
A -> C, the effect produced will be quite different. Under
these circumstances substance A will be converted almost
entirely to substance D while B and C will be present in
barely perceptible or imperceptible traces.
The substance D which is formed in this way, like sub-
stance A or any other organic compound, has many chemical
potentialities and also follows the fastest course in its chemical
transformations. The compound N which is formed from it
may similarly form the starting point for further chemical
transformations. In this way there arises a chain of successive
reactions, related to one another in time, the co-ordination
of which is based upon the relative reaction velocities.
--> etc.
Such chains of successive transformations form the basis of
biological metabolism, in particular the synthesis of the most
complicated components of protoplasm. For example, as we
saw in Chapter V, porphyrin is formed in living cells from
the relatively simple compounds glycine and succinic acid.
This, however, can only occur as a result of a long series
of strictly co-ordinated chemical transformations. First the
succinic acid forms succinyl coenzyme A, by means of which
it condenses with the a-carbon atom of glycine. This reaction
gives rise to a-amino-^-oxoadipic acid, which is converted to
\
\ T'
t
t
< —
--©--
-->©-
--->®--
-->©-
1
1
i/ \
^ \
INITIAL SYSTEMS 335
8-aminolaevulinic acid by decarboxylation. Two molecules of
the latter condense to form porphobilinogen and four mole-
cules of porphobilinogen give a porphyrin structure which
forms protoporphyrin by decarboxylation and dehydrogena-
tion of the side chains/*
Each link in this chain of chemical transformations
requires the participation of specific catalysts, enzymes. It is
only because of this that each product of a preceding reaction
enters into the proper succeeding reaction in the chain and
does not wander off into the many other reactions which are
thermodynamically possible for it.
The initial systems from which
living things arose.
Something similar to this series of chemical reactions must
have taken place in the hydrosphere leading up to the prim-
ary syntheses of porphyrins and other complicated organic
compounds. The nature of these chains of reactions of com-
plicated organic substances which preceded the appearance
of life is therefore very important in connection with our
problem.
It may now be taken as an established fact that in such
simple reactions occurring in the gaseous phase as the oxida-
tion of the louver hydrocarbons or other similar reactions
which took place in the primaeval atmosphere, an essential
part was played by the free radicals which were initially
brought into being by the action of radiations or electric
discharges and perpetuated in the course of chain reactions.
For example, the passage of an electric discharge through
water vapour leads to the formation of hydroxyl radicals
which can oxidise hydrocarbons according to the following
scheme^^:
H.o >OH + H the initiation of the chain
' Uhe continuation or the chain
R + Oo > M2 + OH etc. j
a particular example is:
CH4 + OH -> CH3 + HoO
CH3 -i-Oo -> HCHO + OH etc.
336 ORGANISATION IN SPACE AND TIME
Thus, it is a peculiarity of chain reactions that a large
number of short cycles of reactions can be carried out by
means of alternating active foci, free atoms or elements, when
the sequence of cycles is initiated by a reaction giving rise
to any of the active particles. At the end of each elementary
cycle there are just the same number of free radicals as there
were at the beginning, which constitutes the essential condi-
tions for the perpetuation of the chain. If a larger number
of radicals is formed at the end of the cycle than were present
at the beginning, there will be a branching of the chains,
the number of elementary cycles will increase with a co-
efficient of multiplication of Km and the rate of progress will
quickly increase. Conversely, if the number of radicals is
less at the end of the cycle than at the beginning, the chains
will be broken and the reaction will get slower or stop.
Unlike the chain reactions based on ions or radicals, the
biologically important elementary cycles based on catalysis
arise in another way. According to the most generally accepted
theory of contact catalysis the reaction occurs directly between
adsorbed molecules and either leads straight to the formation
of the final products or first to the formation of an inter-
mediate compound. This then breaks down to form the final
product of the reaction, leaving the original molecule of the
catalyst (e.g. the enzyme) free.
It is true that N. Semenov*" has recently suggested that
heterogeneous catalytic reactions are also based on an inter-
mediate ionic or radical mechanism, but, however this may
be, the elementary cycles of catalysis end with the formation
of thermodynamically stable molecules, and not with that
of free radicals like chain reactions. We must here lay special
stress on the fact that the chain reactions which form the
basis for biological metabolism are different in principle
from the chain reactions described above, which undoubtedly
played an important part in the early stages of the evolution
of organic substances. The separate links in biological chains
are not free radicals but stable molecules, the transformation
of which takes place, in the great majority of cases, without
the regeneration of one or more of the original components,
while the products arising as a result of one reaction enter
into a new chemical transformation, which is different from
INITIAL. SYSTEMS ?^37
the preceding one. Thus biological chains are formed of
different links succeeding one another in a definite sequence
of different reactions and do not consist of a continual repeti-
tion of one and the same chemical act, as do the chain
reactions of free radicals. This may be illustrated by the
example of the biosynthesis of porphyrin which we have
already adduced, or by alcoholic fermentation, in the course
of which a molecule of sugar successively enters into reactions
of phosphorylation, enolisation, the breakdown of the carbon
chain, oxido-reduction, decarboxylation, etc., giving rise to
new products each time, right up to the final products,
carbon dioxide and alcohol, which are discharged from the
cell into the external medium.
Biological chains of chemical transformations may branch,
but this phenomenon is fundamentally different from the
branching of chain reactions (of the radical or ionic type)
based on an increase in the number of radicals formed and
hence an increase in the number of identical cycles of
reactions. The branching of biological chains, on the other
hand, consists in the occurrence of reactions going in different
directions. For example, in a chain of transformations of
organic acids, fumaric acid may give rise to succinic acid but
it may also be converted to aspartic acid" : Pyruvic acid -^
^ aspartic acid
oxaloacetic acid -^ malic acid -> fumaric acid
"^ succinic acid.
After a long series of reactions biological chains may join up
to form cycles, (e.g. the tricarboxylic acid cycle of Krebs,
which we discuss in more detail below) but these cycles have
nothing in common with the elementary cycles of chain
reactions. They are always associated with irreversible
branchings and therefore biological metabolism as a whole
always proceeds in the same direction^^ and is a flowing
system such as those described during our discussion of open
systems.
This difference in principle between radical chain re-
actions and biological chains must be kept in mind because
there have recently appeared in the scientific literature
attempts to explain the origin of the organisation of proto-
22
338 ORGANISATION IN SPACE AND TIME
plasm in time on the basis of its derivation from the ordinary
chain mechanism.
As an example of this we may cite N. Akulov's book The
theory of chain processes/^ a quarter of which is devoted to
our problem. The theoretical merit of this part of the book
lies in the adoption of a kinetic approach to the problems of
the evolution of chemical forms of the movement of matter
rather than a simplified explanation of this evolution in
terms of increasing complexity of structure. Akulov's factual
working out of the problem cannot, however, be held to be
successful for, instead of the chains of chemical transforma-
tions of different molecules, each of which is thermodynami-
cally stable, such as are characteristic of metabolism, he refers
to the chain reactions of radicals which are different in prin-
ciple, in which there is a ' multiplication ' of identical cycles
such as is found in chain reactions in gases. Also, in Akulov's
scheme, the co-ordination of reactions in time and space is
supposed to be able to exist, in principle, even in a homo-
geneous solution, whereas the organisation of protoplasm
corresponds more nearly to the sequence of chemical reactions
which takes place in an open stationary system. This requires
heterogeneity and the presence of a structure which secures
a definite distribution of the components of the system and
demarcation of the system from the external medium.
A more reasonable outlook on the course of development
of * prebiological ' organic chemical processes has been sug-
gested by J. W. S. Pringle.^* Like Akulov, Pringle starts from
chain reactions of radicals. But as it is quite evident to him
that such chain reactions do not occur in contemporary
organisms, he assigns a part to them only in the early stages
of the evolutionary process. He considers that what character-
ises living things is a series of reactions in which the entropy
of the system is decreased at the expense of an increase of
entropy in the external medium.
According to Pringle such a localised decrease in entropy
depends on the carrying out of autocatalytic reactions in
living systems. However, he uses the term ' autocatalysis '
(only for lack of a better one) not in the usual sense (meaning
that each molecule of protein or nucleic acid gives rise
directly to another just like itself) but to refer to a dynamic
INITIAL SYSTEMS 339
continuity in the evolution of the whole living system. In
this connection it is easy to understand Hinshelwood's point
of view on our problem. He states that the processes of auto-
synthesis do not occur by the isolated self-reproduction of
cellular structures but arise as a result of the co-ordinated
interaction of all the cellular processes. Hinshelwood there-
fore refers very sceptically to the theory that the gene is
endowed with a * mystical ability to reproduce itself '.
Concentrating on the dynamic aspect of the problem,
Pringle devotes his paper essentially only to a study of the
possibility of the development of organisation in time in open
systems. Pringle discusses their organisation in space very
vaguely. He bases his ideas on the materialistic approach
of A. M. Turing^^ whose computations showed that some
kinds of dynamic systems which were originally homogene-
ous could undergo such progressive modification that they
became heterogeneous, the dissolved substances being con-
centrated locally without invoking adsorption on pre-existing
particles.
Hence, in a completely homogeneous system it is hard to
predict the site where local concentrations will occur, because
this is determined by random oscillations and the rates of
different reactions. Such a system would be unstable in
respect of these local concentrations and would tend to stabil-
ise itself, and this offers a mechanism for the formation of
structures where there were none before. If there is any
initial heterogeneity it may provide a focus for morpho-
genesis. However, according to Pringle such a morphogenetic
process demands the complete absence of turbulence in the
waters of the ocean and can therefore only take place at great
depths.
Thus, in Pringle's view, the open system as it first arose
had no real boundaries and merely consisted of local increases
in the concentration of reacting substances at some points in
the primaeval ocean.
M. Ycas^* goes even further in this direction in his observa-
tions on the origin of life. He gives a rather interesting
diagram of the interaction of catalytic cycles, according to
which a product of a reaction in cycle A increases the limit-
ing rate of a reaction in cycle B and, conversely, a product
340
ORGANISATION IN SPACE AND TIME
of a reaction in cycle B increases a particular rate of a
reaction in cycle A (Fig. 34).
As we see from the diagram, the boundaries of such an
open system are no less than the surface separating the ocean
from the atmosphere all over the world. And the author
does indeed consider that in the first stage of evolution there
were no discrete systems, there was only one living thing,
the ' metabolising ocean '. If the problem is formulated in
this way, however, one can hardly speak (as the author does)
of any ' natural selection ' of systems.
Fig. 34. Diagram of the interaction of cata-
lytic cycles (after Yeas). Explanation in text.
The Japanese scientist M. Sugita" takes an opposing view.
He bases his approach to the problem of the origin of life
on a study of thermodynamically irreversible reactions in
open systems and holds that it is on the basis of these very
processes that there must have occurred the formation of
molecular swarms and fluctuations leading to the develop-
ment of coacervate structures.
As we saw on p. 326, any open system must have definite
boundaries separating it from the external medium, which
are represented in the scheme given by dotted lines. This is
necessary because if any form of energy is to be made to do
useful work there must be a spatial separation of the com-
ponents of the system, and this is determined by its structural
BIBLIOGRAPHY 34 1
organisation. Without any such organisation, within a simple
homogeneous sohition, the free chemical energy which is
liberated by the reacting substances could only be distributed
in the form of heat and would be dissipated uselessly. There-
fore an open system which can do work can only exist when
the components are separated from one another in space
within the framework of a definite structure.
Any system which could serve as a starting point for the
evolution of matter on the way to the origin of life must have
been based on the principles of organisation in space and
time which characterise all living things without exception.
As we saw above, this condition is fulfilled by a drop of a
complex coacervate formed of polypeptides, polynucleotides
and other substances of high molecular weight and having
the properties of an open system with its characteristic net-
work of reactions which are interdependent in time.
We cannot, however, rightly regard a system of this kind
as being already alive. Only by a process of progressive
evolution could the simplest living bodies arise from it.
BIBLIOGRAPHY TO CHAPTER VII
1. A. KossEL. Hoppe-Seyl. Z., 22, 176 (1896).
F. W. TiEBACKX. Kolloidzschr., 8, 198 (1911).
2. W. OsTWALD and R. Kohler. Kolloidzschr., ^^, 131 (1927).
3. H. G. Bungenberg de Jong. Protoplasma, i^, 1 10 (1932).
4. G. Gavoret and J. Duclaux. /. Chim. phys., 42, 41 (1945).
H. R. Kruyt (ed.). Colloid Science, Vol. 2. Amsterdam,
1949-
Sadhan Basu and Gurucharan Bhattacharya. Science, 11^,
544 (1952).
5. H. G. Bungenberg de Jong and J. M. F. Landsmeer. Rec.
Trav. chim. Pays-Bas, 6^, 606 (1946) ; Proc. Acad.
Sci., Amst., 5/, 295 (1948).
6. H. Pirenne. Rev. univ. Min., 13, 227 (1937)- Through
Chem. Abstr., 57, 4872 (1937)-
7. H. G. Bungenberg de Jong and K. C. Winkler. Z. anorg.
Chem., 232, 119 (1937).
8. N. E. Prikhid'ko and V. S. Molchanov. Kolloid. Zhur., i^,
450 (1950-
342 ORGANISATION IN SPACE AND TIME
9. Z. A. RoGoviN and N. A. Tsaplina. Kolloid. Zhur., 6, 449
(1940).
10. H. G. BuNGENBERG DE JoNG. Proc. Acdd. Sct., Amst., 50, 707
(1947)-
n. (III. 58).
12. S. Papkov. Kolloid. Zhur., iS, 72 (1956).
13. H. G. BuNGENBERG DE JoNG. La coacervatioH, les coacervats
et leur importance en biologie. (Actualites sci.
industr., no. 398). Paris, 1936.
14. A. Tager. Rastvory vysokomolekulyarnykh soedinenii. Mos-
cow (Goskhimizdat), 1951.
15. G. Galeotti. H oppe-Sey I. Z.,^o, /^g^ (igo^).
16. H. Chick and C. J. Martin. /. Physiol., 40, 404 (1910) ; 4^,
1 (1911); ^5, 61, 261 (1912); Biochem. J., y, 380
(1913)-
17. S. Papkov^ Z. A. Rogovin and V. A. Kargin. Zhur. fiz.
Khim., 10, 156 (1937).
S. Papkov, V. A. Kargin and Z. A. Rogovin. Zhur. fit.
Khim., 10, 607 (1937).
Z. A. Rogovin, V. A. Kargin and S. Papkov. Zhur. fiz.
Khim., 10, 793 (1937).
V. A. Kargin, S. Papkov and Z. A. Rogovin. Zhur. fiz.
Khim., i^, 206 (1939).
A. Tager and V. A. Kargin. Zhur. fiz. Khim., i^, 1029
(1941)-
18. T. B. Osborne and E. Strauss in Handbuch der biologis-
chen Arbeitsmethoden (ed. E. Abderhalden). Abt. I,
Teil 8, p. 383. Berlin and Vienna, 1922.
19. W. Bladergroen. Physikalische Chemie in Medizin und
Biologie. Basel, 1945.
20. H. G. BuNGENBERG DE JoNG. Kolloidzschr., 80, 221 (1937).
21. H. L. Booij, C. J. Vogelsang and J. C. Lycklama. Proc.
Acad. Sci., Amst., 55^ 59 (1950).
H. L. Booij and D. Vreugdenhil. Proc. Acad. Sci., Amst.,
5^, 299 (1950).
H. L. Booij, J. C. Lycklama and C. J. Vogelsang. Proc.
Acad. Sci., Amst., 55^ 407 (1950).
H. L. Booij, C. J. Vogelsang and J. C. Lycklama. Proc.
Acad. Sci., Amst., 5^, 882 (1950).
H. L. Booij and E. S. van Calcar. Proc. Acad. Sci., Amst.,
55. 1169 (1950).
H. L. Booij, J. C. Lycklama and C. J. Vogelsang. Proc.
Acad. Sci., Amst., 5^, 1413 (1950).
BIBLIOGRAPHY 343
22. A. S. Troshin. Byull. eksp. Biol. Med., ^i, 180 (1951).
23. D. G. Dervichian. Research, Lond., 2, 210 (1949).
24. D. Dervichian and C. Magnant. Bull. Soc. Chim. bioL,
Paris, 2j, 101 (1945).
25. W. OsTWALD and R. H. Hertel. Kolloidzschr., ^y, 258, 357
(1929)-
W. OsTWALD. Kolloidzschr., ^g, 60 (1929).
26. P. KoETS. J.phys. Chem.,^0, 1191 (1936).
27. (VII. 23).
28. A. I. Oparin, T. N. Evreinova, T. A. Shubert and M. N.
Nestyuk. Doklady Akad. Nauk S.S.S.R., 10^, 581
(1955)-
T. N. Evreinova, T. A. Shubert and M. N. Nestyuk.
Doklady Akad. Nauk S.S.S.R., 10^, 137 (1955).
29. A. I. Oparin and T. N. Evreinova in Novye dannye po
probleme razvitiya kletochnykh i nekletochnykh form
zhivogo veshchestva. Trudy Konferentsii Akad. med.
Nauk S.S.S.R., p. 231. Moscow (Medgiz), 1954.
30. T. N. Evreinova and N. V. Korolev. Doklady Akad. Nauk
S.S.S.R.,87,ios(ig^2).
T. N. Evreinova. Biofizika, i, 167 (1956).
31. A. A. HoRVATH. Chem. & Ind., ig^y, 735.
32. H. G. Bungenberg de Jong and A. de Barker. Proc. Acad.
Sci., Amst., ^8B, 331 (1955).
33. A. I. Oparin, M. S. Bardinskaya, S. S. Melik-Sarkisyan and
K. B. Serebrovskaya. Doklady Akad. Nauk S.S.S.R.,
108, 1125 (1956)-
34. G. A. Deborin and L. B. Gorbacheva. Biokhirniya, 18, 618
(1953)-
35. T. N. Evreinova. Uspekhi sovremennoi Biol., 57^ 177 (1954).
36. H. L. Booij. Rec. Trav. hot. neerl., ^j, 1 (1940).
K. G. A. Pankhurst in Surface chemistry, p. 109. Special
supplement to i?e?5efl re /?. London, 1949.
37- (VII- 13)-
38. A. Frey-Wissling. Submicroscopic morphology of proto-
plasm and its derivatives (trans. J. J. Hermans and
M. Hollander). Amsterdam, 1948.
39. A. Frey-Wissling. Die submikroskopische Struktur des Cyto-
plasmas. Protoplasmatologia (ed. L. V. Heilbrunn
and F. Weber). Vol. II/A/2. Vienna, 1955.
40. L. V. Heilbrunn. Amer. Nat., 60, 143 (1926).
344 ORGANISATION IN SPACE AND TIME
41. D. Sabinin. Fiziologischeskie osnovy pitaniya rastenii. Mos-
cow (Izd. AN SSSR), 1955.
42. C. Nageli and C. Kramer. Pflanzenphysiologische Unter-
suchungen. Zurich, 1855.
43. W. KiJHNE. Untersuchungen iiber das Protoplasma und die
Contractilitdt. Leipzig, 1864.
44. W. Pfeffer. Osmotische Untersuchungen. Leipzig, 1877.
45. L. V. Heilbrunn. The colloid chemistry of protoplasm in
Protoplasma-Monographien, Vol. 1. Berlin, 1928.
46. W. W. Lepeschkin. Protoplasma, ^^, 1 (1939).
47. W. Seifriz. Advanc. EnzymoL, y, 35 (1947).
48. D. Sabinin. Mineral'noe pitariie rastenii. Moscow and Lenin-
grad (Izd. AN SSSR), 1940.
49. D. Nasonov and V. Aleksandrov. Reaktsiya zhivogo vesh-
chestva na vneshnie vozdeistviya. Moscow and Lenin-
grad (Izd. AN SSSR), 1940.
50. A. GuiLLiERMOND. The cytoplasm of the plant cell (trans.
L. R. Atkinson). Waltham, Mass., 1941.
P. Makarov. Preface to Tsitologiya rastenii i ohshchaya
tsitologiya by P. Danzhar (Pierre Dangeard). Moscow
(IL), 1950.
51. A. S. Troshin. Problema kletochnoi pronitsaemosti. Moscow
and Leningrad (Izd. AN SSSR), 1956.
52. P. Rebinder and K. Pospelova. Introductory paper in
Emulsii by V. Kleiton (W. Clayton). Moscow (IL),
1950-
53. H. G. Bungenberg de Jong and C. Mallee. Proc. Acad. Sci.,
Amst.,^6B,20^ (1953)-
H. G. Bungenberg de Jong, C. R. van Someren and F.
Klein. Proc. Acad. Sci., Amst., ^jB, 1 (1954).
54. M. A. Lauffer and W. M. Stanley. /. biol. Chem., 12^,
b^l (1938)-
55. H. G. Bungenberg de Jong. Proc. Acad. Sci., Amst., ^8,
426 (1935)-
56. H. G. Bungenberg de Jong and H. J. C. Sengers. Rec.
Trav. chim. Pays-Bas, 55^, 171 (1934).
57. H. G. Bungenberg de Jong and J. L. L. F. Hartkamp. Rec.
Trav. chim. Pays-Bas, 55^ 622 (1934)-
H. G. Bungenberg de Jong and O. Bank. Protoplasma, ^},
321,512 (1939); 34> 1 (1940)-
H. G. Bungenberg de Jong and A. de Haan. Biochem. Z.,
^63, 33 (1933)-
58. H. G. Bungenberg de Jong, O. Bank and E. G. Hoskam.
Protoplasma, 3^, 30 (1940).
BIBLIOGRAPHY
345
59. I. N. SvESHNiKOVA. Doklddy Akad. Nauk S.S.S.R., 84, 797
(1952)-
60. N. L. Fel'dman. Doklady Akad. Nauk S.S.S.R., ^4, 1139
(1950) ; 89, 343 (1953).
61. D. Sabinin. Tezisy dokladov soveshchaniya po fiziologii ras-
tenii. Moscow and Leningrad (Izd. AN SSSR), 1940.
62. D. Nasonov. Foreword to (VII. 51).
63. A. S. Troshin. (VII. 22).
64. A. Kriss. Personal communication.
65. Heraclitus of Ephesus. Fragments. See books cited in
(VI. 118).
66. R. Schoenheimer. The dynamic state of body constituents.
Cambridge, Mass., 1942.
67. I. MicHURiN. Sochineniya (2nd edn.). Moscow (Sel'khozgiz),
1948.
T. Lysenko. Agrobiologiya (5th edn.). Moscow (Sel'khozgiz),
1948.
68. (III. 75).
69. K. G. Denbigh. The thermodynamics of the steady state.
London and New York, 1951.
70. R. B. Parlin, R. J. Marcus and H. Eyring. Proc. nat. Acad.
Sci., Wash., 41,^00 (1955).
71. A. C. Burton. /. cell. comp. Physiol., 14, 327 (1939).
72. K. G. Denbigh, M. Hicks and F. M. Page. Trans. Farad.
Soc.,44,4'jg (1948)-
73. A. G. Pasynskii and V. P. Blokhina. Biokhimiya, 21, 826
(1956)-
74. (III. 74).
75. A. C. R. Dean and C. N. Hinshelwood. Progress in Bio-
physics, 5, 1 (1955).
76. A. G. Pasynskii. Uspekhi sovremennoi Biol. (In press.)
77. A. I. Oparin. Article ' Zhizn ' (Life) in Bol'shaya Sovetskaya
Entsiklopediya (2nd edn.). Vol. 16, p. 139.
78. D. Shemin. Conferences et Rapports, ^-eme Congres inter-
national de Biochimie, Bruxelles, 1-6 Aout ip$$, p.
197. Liege, 1956.
79. A. B. Nalbanyan and N. M. Emanuel (ed.). Kinetika tsep-
nykh reakstii okisleniya (Collection of papers). Mos-
cow and Leningrad (Izd. AN SSSR), 1950.
80. N. Semenov. O nekotorykh problemakh khitnicheskoi kine-
tiki i reaktsionnoi sposobnosti. Chapter 9. Moscow
(Izd. AN SSSR), 1954.
81. V. L. Kretovich. Osnovy biokhiynii rastenii. Moscow
(Sovetskaya Nauka), 1956.
346 ORGANISATION IN SPACE AND TIME
82. N. SisAKYAN. Biokhimiya obmena veshchestv. Moscow (Izd.
AN SSSR), 1954.
83. N. Akulov. Teoriya tsepnykh protsessov. Moscow (Gos. Izd.
tekhnoteoreticheskoi Literatury), 1951.
84. J. W. S. Pringle. Symp. Soc. exp. Biol., y, 1 (1953).
85. A. M. Turing. Phil. Trans., 2^'jB, 37 (1952).
86. M. YcAS. Proc. nat. Acad. Sci., Wash., 41, 714 (1955)-
87. M. SuGiTA. Kobayasi Institute of Physical Research : Bulle-
tin, ^, 171 (1955).
CHAPTER Vlll
THE ORIGIN OF THE
FIRST ORGANISMS
The evolution of the initial systems.
Anyone looking at nature around him will, almost un-
erringly, divide it into the world of the lifeless and inorganic,
and the world of living things. The world of living things
is made up of a tremendous variety of animals, plants and
microbes which are widely different from one another.
Nevertheless, among all this diversity, even a person without
scientific experience will notice something common to all
living things, something which relates them to one another
and distinguishes even the very simplest organism from
objects belonging to the inorganic world. This direct, and
sometimes even unconscious, assumption of the ordinary man
concerning the world around him itself contains the most
primitive as well as the most general definition of life.
The age-long philosophical quarrels and acrimonious
differences of opinion on this subject are fundamentally
simply concerned with the question as to what is the essence
of this ' something ' — the essence of life. The idealists see
it as something spiritual, the essential nature of which is
inaccessible to experimental study, while, according to the
materialists, life, like everything else in the world, is material
in nature and an explanation of it does not call for the
acknowledgement of anything supernatural.
Quite large numbers of scientists now take the view that
an understanding of life in general involves no more than a
very thorough knowledge of physics and chemistry and a
very thorough explanation of all vital phenomena in terms
of physical and chemical processes. According to this view
there are no specifically biological laws, and the rules which
prevail in the inorganic world also govern all the phenomena
347
348 THE FIRST ORGANISMS
taking place in living organisms. But this amounts to
denying all the essential differences between organisms and
the objects of the inorganic world, which is fundamentally
unsoimd. Certainly life is material in nature, but it is not
inherent in every sort of material. It is a manifestation of a
special form of motion which we only find in organisms and
which is absent from the objects of the inorganic world. This
form of the motion of matter, in addition to obeying the
general physical and chemical laws, also has its own specific
laws. If one is to understand life it is therefore important
to take into account these qualitative differences from other
forms of motion.
Outstanding scientists and thinkers of past centuries and
of the present time have formulated numerous definitions of
life which, to a greater or lesser extent, indicate what is
specific to it.
We cannot discuss all these definitions in any detail and
shall here confine ourselves to one which was given by F.
Engels as early as the end of the nineteenth century but
which still remains extremely pertinent. " Life is the mode
of existence of albuminous substances and this mode of
existence essentially consists in the constant self-renewal of
the chemical constituents of these substances."^
Thus Engels characterises albuminous substances as the
material bearers of life, and metabolism as their essential
function ; from this all the rest of the most general attributes
of life may be derived. In doing so we must not, as was
pointed out in Chapter VI, identify the ' albuminous sub-
stances ' referred to by Engels with the individual proteins
which can now be isolated from living organisms.
Nevertheless, such unjustifiable identification has formed
the basis of several attempts in the recent literature^ to
interpret as metabolism the reactions observed by a number
of authors,^ in which amino acids containing isotopically
labelled atoms are incorporated into isolated proteins, some-
times involving the substitution of amino acid radicals within
the protein molecule. Such an interpretation clearly derives
from a confusion between two completely different concepts :
(1) biological metabolism in the sense which was described
in the previous chapter, i.e. the orderly sequence of processes
THE PRINCIPLE OF SELECTION 349
which seems to be the prerequisite for the existence of any
hving thing, and (2) ' exchange reactions ' or substitution
reactions in the purely chemical sense, i.e. phenomena in the
course of which two molecules of organic substances or even
inorganic salts exchange their atomic groups, e.g. :
CH3COOC2H5 + HOC5H11 ^=^ CH3C00C5H11 + HOC2H5
Undoubtedly the molecules of any protein, with their exten-
sive chemical potentialities, can take part in such substitu-
tion reactions, but, unlike biological metabolism, these re-
actions are certainly not absolutely necessary to the existence
of the protein molecule. It is well known that individual
proteins isolated from living things can be kept under suit-
able conditions in the native state without any such reactions
taking place, while an increase in their ability to enter into
such reactions may be an indication of denaturation of the
protein.*
In contrast to this, metabolism is certainly a necessary
condition for the existence of protoplasm or ' albuminous
substances ' in the sense in which Engels understood the
term.
Engels wrote^ :
From the moment when this uninterrupted metamorphosis of
its constituents, this constant alternation of nutrition and excre-
tion, no longer takes place in an albuminous body, from that
moment the albuminous body itself comes to an end and de-
composes, that is, dies.
As we said in the preceding chapter, it follows from the
very theory of open systems® that the continuous renewal of
the component parts is a necessary condition for the existence
of such systems ; that as soon as the flow of water from the
tap, or, in the hydrodynamic model, the admission of water,
ceases then the system itself immediately ceases to exist as
such. Similar considerations apply to any chemical open
system.
The principle of selection.
However, living things differ fundamentally from all such
open systems in the orderly regulation of their metabolism
350 THE FIRST ORGANISMS
and the ' purposefulness ' of their internal structure. Not
only are the many tens and hundreds of thousands of chemi-
cal reactions which occur in protoplasm, and which together
constitute its metabolism, strictly co-ordinated with one
another in time, harmoniously composed into a single series
of processes which constantly repeat themselves, but the
whole series is directed towards a single goal, towards the
uninterrupted self-preservation and self-reproduction of the
living system as a whole in accordance with the conditions
of the surrounding medium.
Here the term ' purposefulness ' should, of course, not be
taken in an idealist sense as the ' fulfilment of some higher
design '. The word is used to denote the appropriateness of
the organisation of the whole system to its self-preservation
and self-reproduction, and also to denote adaptation of the
structure of its separate parts to the most efficient and
co-ordinated fulfilment of those functions necessary to life
which these parts subserve in the system as a whole.
The high degree of adaptation of the separate organs to
the carrying out of their functions and the general ' purpose-
fulness ' of the whole organisation are extremely evident
even from a superficial knowledge of higher living things.
They were noticed by mankind a very long time ago and
were expressed by the 'entelechy ' of Aristotle. The essential
nature of this purposefulness appeared to be mystical and
supernatural until Darwin gave a rational and materialistic
explanation of the way in which this ' purposefulness ' could
arise as a result of natural selection.
However, ' purposefulness ' of structure is not confined to
higher beings, it extends downwards through the whole
world of living things, right to the bottom, to the most ele-
mentary forms of life. It is essential for any living body but
is absent from the objects of the inorganic world. The only
exceptions are machines, but the purposefulness of their
structure, their adaptation to the performance of particular
tasks, is determined by the creative intention of those who
build them. Machines cannot arise of their own accord by
purely physical and chemical means. It is therefore pointless
to seek an explanation of them in purely physical and
chemical terms. The origin of the organisation of protoplasm
THE PRINCIPLE OF SELECTION 35I
which characterises living organisms, biological metabolism,
is understandable only on the basis of the same principles
which govern the origin of the ' purposefulness ' of the struc-
ture of higher organisms, that is to say, on the basis of the
interaction between the organism and the environment and
on the basis of the Darwinian principle of natural selection.
This new biological law arose during the actual process of
the establishment of life and later took a leading part in the
development of all living matter.
But can this law be applied to any system other than the
living organism? As we have already seen (cf. p. 261) the
attempt to apply the principle of natural selection to the
evolution of separate molecules cannot be held to be satis-
factory. However, we shall adopt a different approach if
we try to imagine the possibility of the evolution of those
systems which we postulated in the previous chapter as being
the starting point on the road to the development of living
systems, that is, to the evolution of the drops of complex
coacervates which have the properties of open systems and
the network of interdependent reactions characteristic of
such systems.
In the very origin of such individual multimolecular
formations there was already inherent the necessity for their
further progressive development. During the time when
organic material was completely merged with its environ-
ment, while it was dissolved in the waters of the primaeval
seas and oceans, its evolution could be considered as a whole.
However, as soon as it became concentrated at definite points,
in colloidal multimolecular systems, as soon as these forma-
tions became separated from the surrounding medium by a
more or less clearly defined boundary and attained a certain
individuality, new and more complicated conditions were at
once created. The later history of any individual coacervate
drop might differ substantially from that of another coexistent
system. The fate of such a drop depended not only on the
general conditions of the external medium, but also on the
specific internal organisation in space and time of the system
in question. The details of this organisation were peculiar
to the particular drop and may have been somewhat different
352 THE FIRST ORGANISMS
in other drops, each system having its own characteristic
pecuHarities.
What were the conditions which determined the existence
of any coacervate drop in the waters of the primaeval hydro-
sphere? Complex coacervates obtained artificially, by simply
mixing solutions of two differently charged colloids, are, as
we have seen, formations with a static stability. The greater
or less duration of their existence is determined by the condi-
tions of solubility or the presence of surface membranes and
is associated with the maintenance of the constancy of the
properties of the system in time.
Thus, in such a coacervate drop, the slower any particular
change takes place and the more constant the surrounding
medium remains, the greater will be the stability of the
system and the less its chance of disappearing as an individual
formation during the time it is under observation under the
conditions of a laboratory experiment.
This, however, was not the sort of stability manifested
by the systems which played the decisive part in the evolution
of matter on the way to the origin of life. This evolution
could only proceed on the basis of interaction between the
systems and the external medium in contact ^vith them, i.e.
on the basis of the formation of open systems. We must
remember that the coacervate drops, w^hich arose somehow
in the primaeval hydrosphere, were immersed, not simply in
water, but in a solution of various organic compoimds and
inorganic salts which were certainly capable of entering into
the coacervate drop and interacting chemically with the sub-
stances of which it was composed. If we do so it will be clear
to us that under these conditions the stability of the drop could
not retain its static nature. The drop would, to some extent,
assume the character of an open system.
This would occur specially readily when the actual
formation of the drop was based on a previous chemical
organisation in time like that postulated by M. Sugita.^
However, let us suppose that the drop arose under purely
colloidal conditions, that the whole process of its formation
resulted simply from the concentration of protein-like sub-
stances and others of high molecular weight at a definite place,
and from the formation of a surface membrane separating
THE PRINCIPLE OF SELECTION 353
the collection of these substances from the external medium.
Even so the molecules of the external medium must ha\e
passed selectively through the surface membrane of the drop
or been adsorbed selectively by the compounds contained in
it and reacted with them in one way or another, the products
of the reaction either being retained within the drop or
passing out of it back into the external medium. Although
these reactions took place very slowly and did not form an
interacting network of processes, and although the conditions
necessary for the prolonged existence and stability of the
coacervate drop were still not present, nevertheless, even at
this primitive stage of evolution of our original systems two
circumstances were manifest which ^vere of great importance
for the further development of matter.
On the one hand the individual peculiarities of the
physico-chemical organisation of each separate coacervate
drop imposed a definite pattern on the chemical reactions
which took place within that drop. The presence in a given
drop of this or that compound or radical, the presence or ab-
sence of simple inorganic catalysts such as salts of iron, copper,
calcium, etc., the degree of concentration of protein-like
substances and other substances of high molecular weight
forming the coacervate, its particular structure, all these
affected the rate and direction of the various chemical
reactions which occurred within the given drop, all these
imparted a specific character to the chemical processes which
took place within it. Thus there appeared a certain con-
nection between the individual structure and organisation
of a given drop and the character of the chemical trans-
formation carried out within it. In other drops these trans-
formations occurred and were co-ordinated in different ways,
depending on the peculiarities of each particular drop.
On the other hand, any chemical processes, even unco-
ordinated ones, occurring within a drop, and, even more,
any connected group of processes, could not be without effect
on its future. Some of them led to greater stability, to a
more prolonged existence of the coacervate system under the
conditions prevailing in the external medium.
From this point of view they were advantageous, they were
of positive significance. On the other hand, other processes
23
354 THE FIRST ORGANISMS
and groups of processes were of a negative character, they
were inimical to the particular individual formation, leading
to its dissolution, to the disappearance of the drop in which
they arose.
However, such coacervate systems cannot have played any
essential part in the further evolution of organic formations
as their individual history was short and quickly brought to
a close. The only systems which maintained themselves in
existence for a more or less prolonged period under the
conditions prevailing in the external medium were those
which had an individual organisation based on chemical
reactions which were favourable for their existence.
Thus, even at this stage of the evolution of matter there
appeared a certain * selection ' of organised colloidal systems
on the basis of the suitability of their organisation to the
function of preserving the uninterrupted interaction of the
system and the surrounding medium under given circum-
stances. This ' selection ' was, of course, of a very primitive
kind and not directly to be compared with fully developed
* natural selection ' in the strictly biological sense of the
term. Nevertheless the further evolution of organic systems
was controlled by ' selection ' of this sort and thus acquired
a definite direction.
Processes of self -renewal of the systems.
In the first place this directed evolution led to an essential
alteration in the character of the stability of the original
colloidal systems. The stability of the coacervate drops which
first arose in the waters of the hydrosphere may originally
have been governed by the same static principles which
govern the stability of coacervates of gelatin and gum arabic
produced artificially in the laboratory.
The coacervate state and the organisation of the processes
taking place within the drop may, to some extent, exist
independently of one another. However, for reasons which
have already been indicated, during the course of directed
evolution these two aspects of the organisation must after-
wards have become more and more unified within the single
system, because the existence of the system depended on a
SELF-RENEWAL OF THE SYSTEMS 355
network of reactions carried out within it while, conversely,
the network was determined by the organisation of the system
as a whole. If the system was not co-ordinated but, neverthe-
less, interacted with the external medium, it would very
quickly disintegrate and disappear as an individual forma-
tion. If the interaction between the system and the medium
stopped for any reason, then the system would become static
and, as such, cease to take part in the general process of
evolution.
For example, if the stability of the drop depended on the
formation of strong surface layers and if these disintegrated
spontaneously at a definite rate but could be built up again
in the course of chemical reactions within the drop, then the
stability of the drop would depend on the relative rates of
disintegration and reconstruction of the surface layers. If
the chemical reactions took place fast enough in the drop,
with a corresponding fast rate of formation of the firm surface
layers, then the dynamic stability of the drop might also be
very great. In this case an increase in the rate of the chemical
reactions within the drop wotild have favoured its stability.
The increased rate of reaction within a drop would increase
its stability, and prolong its survival under such conditions.
If the rate of formation of the surface layers became less than
the rate of their destruction such a drop would soon dis-
integrate. Finally, if the surface layers themselves were very
strong and stable but not associated with any cheinical
reactions within the drop, then such static colloidal systems
would be excluded from the course of the evolutionary
process.
Accordingly, as a result of the directed evolution of the
original systems, their stability took on a more and more
dynamic character. The coacervate drops were gradually
transformed into open systems the very existence of which,
under the given conditions of the external medium, depended
on the organisation of the processes taking place within them.
In other words, there arose systems in which there was a back-
ground of continuous processes of self-renewal and which
could preserve themselves and exist for a long period on the
basis of constant interaction with the external medium. The
origin of this capacity for self-preservation may be regarded
356 THE FIRST ORGANISMS
as the first result of the directed evolution of our original
systems.
The origin of the capacity of the systems
for self-preservation and growth.
The second step forward in the same direction was the
emergence of systems which could not merely preserve them-
selves, but could also grow, increasing their mass by drawing
substances from the external medium. As was pointed out
in the previous chapter, the stationary state of open systems
is maintained constant, not because the free energy of the
system is at a minimum as in thermodynamic equilibrium,
but because the system is continually receiving free energy
from the surrounding medium in an amount which compen-
sates for the expenditure of free energy within the system.
In such chemical open systems as the coacervate drops of the
primaeval ocean would seem to have been, the intake of free
energy was mainly due to the entry into the drop of organic
compounds which were relatively rich in energy and which
underwent some sort of chemical reaction within the drop.
When chemical reactions are taking place, however, closed
and open systems differ from one another in that in the
former equilibrium is characterised by the reaction occur-
ring at the same rate in both directions so that, in the nature
of things, there can be no increase in mass. In open systems
in the stationary state, on the other hand, the rate of the
reaction is considerably greater in one direction than in the
other, and it follows that there may exist in them a co-
ordination of processes leading to an increase in the mass of
the system. Such systems enjoyed an undoubted advantage
in the process of directed evolution and therefore, owing to
the action of ' selection ', they came to occupy a predominant
position in the general extension of organised formations.
In the absence of any appropriate experiments, even with
models, one cannot say anything definite about the nature
of such growth in our original systems. They might have
become larger in the form of uniform layers of coacervate,
but they might also have become divided into separate drops.
SELF-PRESERVATION AND GROWTH 357
Drops of liquid having a limited mutual solubility or artificial
static coacervates cannot divide themselves spontaneously.
The forces of surface tension are always tending to make them
coalesce and it is only the presence of surface membranes
which, to some extent, prevents this from happening. How-
ever, as we know, dispersion of this sort may be achieved,
even in such static systems, by means of external influences
such as simple shaking, which may lead to emulsification.
The dispersion of the primaeval gi^owing coacervate may
also have occurred in this way. However, as these were of
the nature of dynamic stationary systems the existence of
which was bound up with the occurrence of processes within
them, their dispersion may have been evoked by internal
factors. It may, for instance, have occurred when the osmotic
pressure, which was increasing rapidly owing to the hydro-
lysis of compounds of high molecular weight, became too
great for the strength of the surface layer of the drop.
Thus, owing to the constant interaction of our original
systems with their environment, there must have occurred
a gradual increase in the amount of material organised in
the systems. But as this increase always occurred under the
influence of ' selection ' the only systems which were pre-
served for further evolution were those which were most
highly developed, so that the quality of this organisation was
always changing in a particular direction. The systems did
not merely become more dynamically stable, they also
became more dynamic. We may regard this phenomenon as
the third important step in the directed evolution of our
original systems on the way to the development of life.
In the first stages of the evolution under consideration,
when one could study the fate of isolated coacervate drops
without taking into account their relation to other such
drops, the factors which Avere of paramount importance for
the prolonged existence of the drop in question as an open
system, for its self-preservation under conditions of constant
interchange with the surrounding medium, -were the relative
rates of the processes taking place within it and not the
absolute values of these rates.
358 THE FIRST ORGANISMS
The origin of the highly dynamic
state of the systems.
The position is radically altered if we include in the field
of our investigations not merely one, but several open
systems, existing simultaneously within a particular medium.
This may be shown even by working with relatively simple
models. For example, when there are several hydrodynamic
stationary systems with common initial and final reservoirs,®
the greater part of the water will proceed through the system
which enables it to pass through most quickly. In the case
of several parallel, chemical open systems with a common
external medium it is obvious that the main flow of sub-
stances will pass through the system which, by virtue of its
internal organisation (e.g. the presence of more efficient
catalysts, etc.), provides the greatest over-all rate of chemical
transformation. In this sense the chemical stationary system
in which chemical processes occur fastest will have an advan-
tage over other parallel chemical stationary systems so long
as the increased rate of occurrence of the processes does not
disturb the relationship of rates necessary for the self-
preservation of the system ; that is to say, if it is compatible
with the prolonged existence of the particular open system.
In this connection we must bear in mind what was pointed
out in the previous chapter, namely that, where there is a
complicated network of chemical reactions, the attainment
of the maximal rate by a process involves not merely the
acceleration of one of the stages of the transformation but
the establishment of a more effective relationship between
all the parameters of the process.^
From what has been said it is clear that a dynamically stable
coacervate drop capable of self-preservation and growth,
which had acquired the ability to transform substances more
quickly during its interaction with the external medium,
would have a significant advantage over other drops which
were immersed in the same solution of inorganic and organic
compounds but in which the characteristic chemical pro-
cesses proceeded considerably more slowly. In the general
mass of coacervates the relative proportion of such more
dynamic drops would become greater and greater. There
ORIGIN OF SELF-REPRODUCING SYSTEMS 359
arose a special kind of competition among the drops, based
on the speed with which reactions were accomplished within
them and the rate of their growth. For this reason the prin-
ciple of the greatest speed (which must, nevertheless, be
compatible with the existence of the stationary system as
such) was a very important factor in the directed evolution
of organised formations.
The origin of systems capable of
reproducing themselves.
It must, however, be pointed out that the capacity for
self-preservation, and even for rapid growth, of the whole
dynamic system did not imply the complete immutability
of the system. On the contrary, the stationary drop of a
coacervate, or any other open system, may be preserved as a
whole for a certain time while changing continually in regard
to both its composition and the network of processes taking
place within it, always assuming that these changes do not
disturb its dynamic stability.
Changes of this sort were, in fact, a necessary part of the
process of the emergence of life for they guaranteed the
evolution of the initial systems. Without these changes no
new material would have been provided for selection and the
further development of the systems would have been frozen
and brought to a standstill at some point.
Naturally, it was of the utmost importance that these
changes should not overstep the bounds of the dynamic sta-
bility of the systems. Otherwise any markedly unstable com-
pounds which arose w^ould be in constant danger of passing
out of equilibrium and disappearing. Therefore, when there
was rapid and massive growth of the original systems, selection
took place, the only ones ^vhich were preserved for further
evolution being those in which the network of reactions was
so co-ordinated that there arose stationary chains of reactions
which were constantly repeated or, even better, closed cycles
of reactions* in which the reactions always followed the same
* Of course these cycles must not, as we have already mentioned in Chapter
VII, be confused with the elementary cycles of chain reactions. — Author.
360 THE FIRST ORGANISMS
circle and branching only occurred at definite points on the
circle leading to the constantly repeated formation of this
or that metabolic product. This constant repetition of con-
nected reactions, co-ordinated in a single network, also led
to the emergence of a property characteristic of living things,
that of self-reproduction. This may be taken as the origin
of life. At this stage in the evolution of matter natural
selection assumed its full biological meaning and formed the
basis for the faster elaboration of higher and higher degrees
of adaptation of living organisms to the conditions under
which they existed, of the exact correspondence of all the
details of their internal structure to their vital functions. In
other words, there appeared that striking ' purposefulness '
of the structure of living bodies upon which we have already
remarked.
The opinion is fairly widely held in contemporary scien-
tific literature that the capacity for self-reproduction is to
be found even in the chemical form of the motion of matter,
that it can be a property of isolated molecules. Until com-
paratively recently many biologists regarded the constant
formation of particular substances within the organism as
being the result of the presence in the organism of ready-
made moulds for those particular substances. These moulds
were supposed to ' multiply ' in some way and thus be
responsible for the constancy of the composition and structure
of the organism and for its reproduction.
In particular this opinion was once very clearly expounded
by N. Kol'tsov.^" He believed that the formation, not only
of proteins, but also of other components of the living cell,
such as chlorophyll and the anthocyanins, occurred because
the protoplasm already contained corresponding molecules
which acted as templates for their formation. These mole-
cules * multiplied ' and thus exactly reproduced their own
structures.
The factual evidence of contemporary biochemistry was,
however, radically opposed to this opinion and revealed a
completely different mechanism of biosynthesis based on the
constancy of certain sequences of biochemical reactions. For
example, butyric acid is formed by some species of bacteria,
not because it was present in them beforehand, but because
ORIGIN OF SELF-REPRODUCING SYSTEMS 36 1
the sugar which is taken up from the surrounding medium
by the bacterial cells is broken down to acetic acid by means
of a series of strictly co-ordinated reactions. The acetic acid
then combines with coenzyme A and is thus enabled to con-
dense to form aceto-acetic acid which is then reduced to
butyric acid/^
If the sequence of these reactions were somewhat different,
the end products might be alcohol and carbon dioxide, as
in yeast, or lactic acid, as in some bacteria. The same principle
of the constancy of a definite sequence of reactions is also
responsible for the synthesis of the higher fatty acids, amino
acids^' and a whole series of other compounds. .
The chemical studies carried out 20 years ago by R.
Robinson^^ and the biological work of R. Scott-Moncrieff^*
showed that the anthocyanins mentioned above arise in the
same way in plants as a result of the occurrence in them
of a definite sequence of reactions of condensation, oxido-
reduction, methylation, acetylation, etc. According to the
order in which these reactions occur in the petals of different
flowers, various derivatives of flavones and anthocyanins are
formed, and the particular combinations in which these
substances are present give the petals their characteristic
colours.
A similar mechanism has also been discovered for the
formation of various terpenes in plants from which essential
oils are obtained.^^ The terpenes appear in them as a result
of sequences of reactions which are specifically determinate
for each plant and include polymerisation, hydration, oxida-
tion and ring formation. The same is true for the synthesis
of tannins,^® alkaloids,^'' vitamJns^* and various porphyrin
derivatives, chlorophyll in particular. ^^ Very detailed evi-
dence has also been obtained recently concerning the bio-
synthesis of such extremely complicated and specific sub-
stances as antibiotics.^" Here also a definite sequence of
chemical transformations is involved.
Thus lactic or butyric acids are formed in particular
species of bacteria, nicotine in tobacco plants, tannin in tea
leaves, vitamins in yeast cells and streptomycin in actino-
mycetes, not because pre-formed molecules of these substances
were already present in the objects in question, but because,
362 THE FIRST ORGANISMS
at a given stage in their life cycles, chemical transformations
are carried out within them in a definite, co-ordinated
sequence. The constancy of the formation of the substances
is simply a manifestation of the constancy of the sequences
of the reactions. Here there is no * self-reproduction ' of
molecules in the literal sense of the term, no multiplication
of them ; here new molecules of exactly the same kind are
repeatedly produced. The sequence of reactions on which
this phenomenon is based does not depend on any single
individual factor but is a manifestation of the whole organisa-
tion of the protoplasm in its relationship to its environment.
As we saw in Chapter VI, the biosynthesis of proteins
constitutes no exception in this respect. Attempts to treat it
as an autocatalytic process, in which one molecule of a given
substance arises as a result of the catalytic activity of another
of exactly the same sort which was already present, have
recently proved a complete fiasco. The experiments of A.
Gierer and G. Schramm^^ are particularly convincing in this
connection. They showed that a single nucleic acid of tobacco
mosaic virus completely freed from protein, when introduced
into the plant, will evoke the formation in it of a specific
protein which was not previously present in the plant. In
this case there could be no question of any autocatalysis in
the strictly chemical sense of the term. There was only
definite co-ordinated interaction of all the processes of the
cells of the tobacco leaf, which were somewhat altered in
character by the introduction of a new factor, the viral nucleic
acid. The nucleic acid as an individual substance, a com-
pound considered in isolation, could certainly not synthesise
a protein by itself. It is only effective against the general
background of the whole metabolism of the tobacco plant,
as is confirmed by all the evidence at present available. The
harmonious participation of a long series of catalytic systems
is required for the biosynthesis of proteins, some providing
the energy needed for the synthesis, some determining the
strictly regular and constant relationship between the rates
of the different reactions and, finally, some systems which
control the spatial organisation of the protein molecule in
the process of its synthesis. Among these systems which deter-
mine the specific structure of the protein, nucleic acid plays
ORIGIN OF ENZYMES 363
a very important part, but it does not seem to be the sole
determinant, it simply constitutes a part of the general
organisation of the living system.
As has been pointed out above, nucleic acid itself also
arises in the living organism in accordance with the same
rules as the other components of the protoplasm, that is to
say, on the basis of strictly co-ordinated, constantly repeated,
catalytically induced exchange reactions. ^^
It is clear that no substance which forms a major com-
ponent of protoplasm can be reproduced by a chance or
easily attained relationship between the rates of reactions. It
requires the absolutely constant, continually repeated chains
and cycles of reactions which together comprise the network
of the self-reproducing, living, open system. As we have seen
above, the origin of such a system may be regarded, theoreti-
cally, as a result of the directed evolution of our original,
dynamically stable, colloidal formations.
The living systems which were first formed already had
all the features needed for their selection to be of the nature
of purposeful ' natural selection ' in the biological sense of
the expression. Further improvements in their internal
organisation, rationalisation of their metabolism, therefore,
went forward at a faster pace. As a direct result of this, all
intermediate forms of organisation were destroyed, swept
from the face of the Earth by natural selection. This is why
we have now no possibility of studying these forms directly
and filling in, with factual material, the abyss which exists
between the organisation of the original systems and the
organisation of even the simplest of present-day organisms.
The evolution of metabolism : the origin
of enzymes.
Experiments with models which reproduce the phenomena
in dynamically stable colloidal formations may, perhaps, play
an important part in this connection. Studies of this sort
are, however, still only beginning to be made* and the
* In particular in the form of attempts to incorporate active preparations
of enzymes in the coacervate drops with a view to conferring some
dynamic character on the drops. — Author.
364 THE FIRST ORGANISMS
results obtained from them are still very modest. Therefore,
if we wish to formulate any sort of idea concerning the actual
forms which developed during the course of evolution from
the original systems to the first organisms, we must make as
much use as possible of the data of comparative biochemistry
(this is done more fully in the next chapter) and the results
obtained from a study of the metabolism, or separate aspects
of the metabolism, of isolated protoplasmic structures and
collections of enzymic systems. In this way we may be able
to reveal various features common to all living organisms
and may try to form a mental picture of how these features
could have arisen during the process of directed evolution
of our original systems or in the earliest stages of the develop-
ment of life.
As we have remarked again and again, the fundamental
organisation of living matter is its organisation in tim.e. The
phenomena which take place in it in a definite, regular order
together constitute its metabolism.
The individual reactions which occur in protoplasm are
rather simple and uniform. They are the reactions, familiar
to chemists, of oxidation, reduction, hydrolysis, phosphoro-
lysis, aldol condensation, the breaking of carbon-carbon
bonds, etc. Any of these may be brought about outside the
organism and there is nothing specifically vital about them.
What would seem to be specific to living bodies is the definite
organisation in time of these reactions in them, to form a
single complete system, an abundantly branching network
of reactions. In living bodies these reactions do not take
place chaotically but bear a strictly determined relationship
to one another. The colossal diversity of organic compounds
which is to be found in the world of living things does not
depend on diversity and complication of the separate indi-
vidual reactions but on the diversity of their combinations,
the variations in the order in which they occur in the
different cells of the organism at particular stages of develop-
ment. This sequence of chemical reactions forms the basis
of both the synthesis and the breakdown of the substances
of protoplasm. It forms the basis of such vital phenomena as
the synthesis of proteins, fermentation, respiration, photo-
synthesis, etc. In the respiratory and photosynthetic processes
ORIGIN OF ENZYMES 365
sugar and oxygen, carbon dioxide and water, are only the
first and last links ; between them there are long chains of
chemical transformations. In these chains the intermediate
product which is produced by one reaction immediately
enters into the next reaction, which is strictly determinate
for the vital process in question. If these sequences are
changed, if any single link in the chain of transformations is
removed or altered, then the whole process will become quite
different or even be thrown right out of action. As we have
seen, these organisational features, which are characteristic
of everything living, are exactly analogous, in principle, to
the network of chemical transformations which forms the
basis of any more or less complicated chemical open system.
As in these systems, so in living things, the characteristic
order of phenomena which has been described is based on
a close co-ordination of the rates of the chemical reactions
which form the individual links of the long and labyrinthine
chain of metabolism.
Organic substances, which are the essential components of
living systems, seem to be the only material which can form
the basis of such chains of reactions. It is characteristic of
these substances that they can react in the most diverse ways.
Although they have tremendous chemical potentialities, these
are only realised extremely slowly under ordinary conditions
and in isolation. This very slow rate of reaction depends
essentially on the gi'eat amount of energy of activation, i.e.
the high energy -barrier "^\^hich molecules of organic substances
must surmount before they can participate in any chemical
reaction. However, depending on all the combinations of
circumstances under which any given reaction takes place,
its velocity may vary within very wide limits.
If the conditions are such that only one of the reactions
possible for any particular organic substance occurs very fast
while all the rest of the possible reactions proceed compara-
tively slowly then, naturally, the practical significance of the
latter will be quite negligible in the over-all result. In other
words, there lie before each organic substance in protoplasm
many routes of chemical transformation which are thermo-
dynamically open to it. In fact, however, each compound
\vhich enters the protoplasm from the environment, and any
366 THE FIRST ORGANISMS
intermediate product which may be formed within the proto-
plasm, will be changed during metabolism only in the direc-
tion in which it can react most quickly. All the rest of the
reactions, which take place more slowly, will simply not have
time to occur to any significant extent. It is in this way that
there are formed those strictly determined chains and cycles
of successive quick reactions which together constitute the
more or less ramifying network of metabolism.
A simple homogeneous mixture of organic substances, or
even a newly formed coacervate drop which has not yet been
transformed into a well-organised open system, presents, from
this point of view, a very wide but completely untrammelled
field of chemical possibilities. The same great difficulties and
obstacles hinder movement in any direction in this field.
In contrast to this, selection has led to the presence in proto-
plasm of definite paths of biochemical processes, a whole
network of ' rationally built roads ' along which there pro-
ceeds at a great rate and in ' orderly columns ' the chemical
transformation of substances and the associated conversion
of energy.
This highly-developed order, which depends on the definite
relationships between the velocities of the reactions, is regu-
lated in the living body by many factors. The most important
of these is the catalytic activity of the enzymes.
Nowadays the study of enzymes, enzymology, has grown
into an extensive and independent field of knowledge in
which an immeasurable amount of work is being done.^*
Many enzymes have now been isolated from living organisms
in the form of highly purified crystalline preparations-^ which
have been studied in detail as regards both their chemical
nature and the mechanism of their catalytic activity.^®
These enzymes have been found, without exception, to be
simple or conjugated proteins. The prosthetic groups of the
latter consist, in most cases, of organometallic compounds or
various vitamins. There can now be no doubt that each cell
contains a whole collection of diverse enzymes and that the
majority of the proteins of the living body have enzymic
activity. Thus enzymes would seem to constitute the bulk
of the proteins of protoplasm. ^^
ORIGIN OF ENZYMES 367
The fact that enzymes seem to be chemically proteins,
having a definite sequence of amino acid residues in their
polypeptide chains and a definite internal structure of their
molecules, determines a number of the peculiarities which
distinguish enzymes from all other catalysts known to us. The
most important of these is their intense catalytic activity.
There are known to be a large number of inorganic and
organic substances which can hasten the same reactions as
those affected by enzymes, but there is no comparison between
the strengths of their catalytic activities. For example,
hydrogen ions can catalyse the hydrolytic reaction whereby
sucrose is hydrolysed to glucose and fructose, a reaction which
is also catalysed by the invertase of yeast, but the enzyme is at
least ten million times as effective. The very simple nitrogen-
containing organic compound, methylamine, increases the
rate of breakdown of pyruvic acid. So does the enzyme
carboxylase, but the catalytic activity of the enzyme is about
thirty million times as great as that of methylamine. The
ferric ion appreciably facilitates the breakdown of hydrogen
peroxide into water and oxygen. The enzyme catalase, which
is a combination of an iron-porphyrin complex with a specific
protein-* has the same effect but brings about the reaction
about 10^" times as fast as inorganic iron.
The complicated structure of the protein molecule is also
responsible for the second important peculiarity of enzymes,
the high specificity of their action. Inorganic catalysts are
rather indiscriminate in their action. For example sucrose,
maltose, starch, proteins and many other substances may all
be hydrolysed equally well by hydrogen ions. But enzymes
act in a highly specific way, only catalysing particular
reactions. They only break the bonds between certain definite
groups of atoms and leave others quite intact, although these
may be very similar to those of their substrates. If, there-
fore, we have any organic substance which is capable of a
number of chemical changes, then, in the presence of any
one enzyme it will react with remarkable speed, but only in
one particular direction. For example, pyruvic acid in the
yeast cell, where the enzyme carboxylase is present, is almost
entirely broken down to carbon dioxide and acetaldehvde
and it is only the acetaldehyde which is reduced to alcohol
368 THE FIRST ORGANISMS
by the action of a specific dehydrogenase. In the lactic acid
bacillus, on the other hand, where there is no carboxylase,
pyruvic acid is reduced directly to lactic acid and is not
decarboxylated to any considerable extent. Thus the highly
specific action of enzymes is a very important factor in the
organisation of protoplasm. Less specific catalysts would not
have this capacity to determine the direction in which any
particular organic substance in the protoplasm would under-
go chemical change.
The mechanism of enzymic reactions has now been studied
from various points of view by many authors but, so far, the
problem cannot be considered to have been solved. In its
most general form, the participation of enzymes in metabol-
ism may be presented as follows: The substance which is
undergoing the reaction in question (the substrate) first
forms a very short-lived intermediate compound with the
enzymic protein. This requires a certain correspondence of
structure between the enzyme and the substrate. If this is
absent no catalysis whatsoever can take place. When this
correspondence exists the reaction between the enzyme and
the substrate requires considerably less energy of activation
and therefore takes place very fast at ordinary temperatures.
However, owing to the specific properties of the enzyme
molecule, the intermediate, enzyme-substrate, compound is
very unstable. It very soon undergoes a further alteration, in
the course of which the substrate is changed in the appro-
priate way and the enzyme is regenerated and can once more
form an intermediate compound with a fresh portion of the
substrate.
Reactions whereby the substrate is transformed without
the help of an enzyme usually require a high energy of
activation and therefore take place so slowly that they cannot
play a decisive part in metabolism, which is rapid. When the
enzyme is present, the high energy barrier seems to be broken
down and the route via the intermediate compound seems
to be considerably easier and faster.
Thus, in order that any chemical ingredient may actually
take part in metabolism, it must first interact with a protein
to form a definite intermediate compound. If not, its chemi-
cal potentialities will be realised so slowly as to be of no
ORIGIN OF ENZYMES 369
significance in the rapidly flowing process of life. Thus the
direction in which any compound is altered in the course of
metabolism depends not only on the molecular structure of
the compound, but also on the enzymic activity of the proto-
plasmic proteins with which it becomes involved in the
course of metabolism.
Thus, in enzymes, living bodies not only have powerful
accelerators of chemical processes, but also an extremely
efficient chemical apparatus which can direct these processes
along strictly determined channels. This is, in fact, the essen-
tial function of enzymes in living bodies, and it must be said
that enzymes are extremely efficient ' instruments ' for the
performance of this function. Their structure is amazingly
precisely adapted to the carrying out of this function in the
organisms. One has but to make a slight change in the struc-
ture of the enzyme complex, to rearrange or block one or
other of the chemical groups of its prosthetic part or to
disturb the structure of its protein component, and the
catalytic activity and specificity of the enzyme are markedly
diminished. Thus, even in enzymes, we can already see the
suitability of structure to function, the internal ' purposeful-
ness ' which is so characteristic of living matter in general.
The study of the formation of enzymes in living bodies,
their biosynthesis, is, as yet, really only just beginning ; most
attention has so far been paid to the question of the ' adap-
tive ' origin of enzymes. "" We know very little about this
matter ; it is only clear that the biosynthesis of enzymes, like
that of proteins and the other components of protoplasm,
must occur by many stages. It is quite unnecessary that, in
the course of this biosynthesis, all the elements out of which
the enzyme complex is ' assembled ' should have been syn-
thesised by one and the same organism. They are very often
taken in ready-made from the environment in the form of
vitamins or parts of vitamins, essential amino acids, etc.
How could such a highly developed catalytic apparatus
have arisen in the first place in the process of the directed
evolution of our original systems?
In Chapter VI it was shown that the ability of enzymes to
carry out their functions in the organism, their great catalytic
activity and specificity, was primarily based on the strictly
24
370 THE FIRST ORGANISMS
ordered arrangement of atomic groups in their complicatedly
constructed molecules. As a result of this, the catalytic activity
of each of the groups and radicals is extremely ' advantage-
ously ' combined with activating groups which considerably
augment their catalytic effects or facilitate the combination
of the enzyme with the substrate. This takes place in
enzyme proteins, in which such a structure is associated with
a definite arrangement of amino acid residues in the poly-
peptide chain and a definite internal structure of the protein
particle as a whole. This is just what may be seen, for
example, in the structure of the prosthetic groups of the
conjugated-protein enzymes.
We have already mentioned the work of W. Langenbeck^^
on the construction of artificial models of the enzyme
carboxylase. In this work the author started from the
observation that such a simple compound as methylamine
can catalyse the reaction of decarboxylation of pyruvic acid,
this catalytic activity being a property of the amino group.
But methylamine itself catalyses this reaction very weakly.
The inclusion of a carboxyl group in the methylamine
molecule increases its catalytic activity 19-fold, although the
carboxyl group itself has no catalytic activity. The catalytic
activity of methylamine derivatives may again be increased
by the further addition of aromatic and heterocyclic rings.
Following this up, Langenbeck finally got a compound
(hydroxyaminonaphthoxindole) which had a carboxylase
activity 4,000 times as great as that of the original methyl-
amine.
Vitamin B, forms the prosthetic group of natural carboxy-
lase from yeast.^^ Its molecule, like Langenbeck's models,
contains a catalytically active amino group which is combined
with two complicated heterocyclic rings. The combination
seems to be more effective here than in the artificial model.
But it is only when vitamin Bj is combined with a specific
protein through a phosphoric group that it acquires the
extremely powerful catalytic activity characteristic of the
enzyme. Neither the vitamin itself, nor the carboxylase
protein, taken alone, have this power and it is only their
combination in a special way which gives the enzyme its great
activity and specificity.
ORIGIN OF ENZYMES 371
This sort of structure of carboxylase is a demonstrable
instance of one case of the internal organisation of proto-
plasm. So long as only the separate parts of the enzyme are
present or these parts are not combined with one another in
a special way, their catalytic activity is small and they carry
out their function in the living body badly. If the enzyme
is to have its characteristic efficiency in this respect its separ-
ate components must be combined together in a special way,
but this cannot occur by chance.
Catalase may serve as another analogous example. As we
have already pointed out, even ferric ions can catalyse the
breakdown of hydrogen peroxide to water and oxygen, but
this is only a weak effect. If the iron is combined with a
porphyrin nucleus to form haemin, the catalytic activity is
increased about a thousand fold. In the natural enzyme,
catalase, the haemin is combined with a specific protein and
this further increases its catalytic activity many million fold.
In the systems which we postulated as being the starting
point for the process of evolution on the Avay to the origin
of life, in coacervate drops having the properties of open
systems, the chemical reactions which formed the network
of the system must, at first, have occurred very slowly. A
certain speeding up of isolated reactions may have been
achieved, mainly by means of the catalytic effect of such
inorganic salts (e.g. those of calcium, iron, copper and vana-
dium) as may have been present in large enough quantities
in the waters of the primaeval ocean.
Certainly even such a very slight increase in rate must
have played a decisive part in the establishment of a definite
sequence of reactions, in the organisation of the network of
chemical processes in our open systems.
In particular, owing to the catalytic activity of inorganic
iron, the breakdown of hydrogen peroxide into water and
oxygen might thus have occupied a place in the network if
it somehow favoured the dynamic stability of the drop, its
preservation for a long time or even its gro^vth under the
conditions of its interaction with the external medium.
NoAV, let us suppose that some of these coacervate drops,
owing to their adsorptive powers or for other reasons, could
2'72 THE FIRST ORGANISMS
take in from the surrounding medium the porphyrins which
were formed there by purely abiogenic means, just as some
contemporary organisms extract from their environment
vitamins which they need for the synthesis of enzymes. On
combining with the iron, the porphyrin would markedly
increase its catalytic activity, and if such a speeding up of
the reaction under discussion was favourable to the dynamic
stability of the drops in which it occurred, then these drops
would enjoy a considerable advantage in the process of selec-
tion compared with other similar systems. Thus the drops
which were preserved for further evolution would be just
those which had a structure enabling them to adsorb por-
phyrins selectively.
Analogous considerations also apply to the formation of
other specific catalysts and enzymes. Even such compara-
tively simple substances as, for example, methylamine,
glycine, aldehydes, sugars, etc., have a weak catalytic activity
for some reactions. These compounds could enter into the
original systems or even, to some extent, be synthesised there.
In the various coacervate drops they could combine with one
another and with the inorganic catalysts present there in
hundreds and thousands of different ways. Among all these
combinations there must certainly have been some in which
the catalytic activity was greatly increased owing to a favour-
able disposition of active and activating gi'oups. A particular
case might be the successful combination of amino acid
residues in the polypeptide chains of the protein-like sub-
stances. This might give marked advantages to the systems
in which there were formed combinations which had a
powerful catalytic activity favourable to their dynamic stabil-
ity and general activity.
This internal chemical rationalisation of the systems was
reinforced by their selection. This destroyed those in which
there had arisen, by chance, ' unsticcessful ' combinations
which diminished the catalytic activity. It preserved for
further evolution only the more efficient catalysts which were
more capable of performing their functions.
ORIGIN OF ENZYMES 373
We have pointed out above that the very highly developed
structures of catalase, carboxylase or any other enzyme could
not have arisen by the action of selection on their separate
isolated molecules, because the reactions which they carry
out are of no significance to the catalase or carboxylase them-
selves. Their hastening or slowing of reactions cannot be
reflected in the length of the existence or an increase in the
amount of the enzymes as such. This activity may, however,
have a decisive effect on the existence of the system in which
any particular catalyst acts. Thus these systems must have
been selected for the characteristic in question, and thus
there could have arisen that extreme ' purposefulness ' of
structure, that correspondence between structure and func-
tion, by which enzymes may be recognised as biological
formations.
Indeed, although we are now very rapidly approaching a
full understanding of the chemical nature of enzymes, and
even the solution of the problem of their synthesis by arti-
ficial means, these catalysts still bear all the marks of their
biological origin. In nature they are only to be found in
organisms and can only be formed naturally there. Such a
' fortunate ' combination of atomic groups as we find in
enzymes, such an intimate association between their struc-
tures and their biological functions, could not have arisen
by chance or simply as a result of the action of the laws of
physics and chemistry. The formation of enzymes required
a definite orientation of the process of the evolution of
matter, it required selection, the destruction of all ' un-
successful ' combinations and the retention for further evolu-
tion of only those systems in which the catalytic apparatus
fulfilled its biological function most rationally.
This evolution of enzymes is still taking place to some
extent. It must, however, be pointed out that the basic forms
of construction of catalytic systems were already elaborated
at what, comparatively speaking, was a very early stage in
the establishment of life and its further development. No\va-
days, therefore, even in the most poorly organised of con-
temporary living things, the individual enzymes are present
as fairly highly-developed formations.
374 THE FIRST ORGANISMS
The origin of the co-ordinated networks
of reactions : the origin of the
first organisms.
Enzymes are, however, only the elementary and simplest
form of organisation of protoplasm, its separate working
mechanisms.
The extreme specificity of protein enzymes means that
each of them can only form intermediate compounds with a
definite very narrow group of substances and can only cata-
lyse strictly determinate individual reactions. However, the
separate reactions catalysed by the different enzymes cannot
of themselves, in isolation, serve as a basis for the process of
life. Their biological significance becomes manifest and well
defined only by virtue of their strict co-ordination with all
the other chemical processes of the living body ; their place
in the general network of reactions in open systems is only
maintained when they are included as essential links in a
long chain of metabolic processes.
Hundreds and thousands of enzyme proteins play their
parts in each vital process, let alone metabolism as a whole.
Each can catalyse only one or a very limited number of
reactions, and it is only when taken together, when their
actions are unified in a definite way, that they constitute
the orderly sequence of phenomena which forms the founda-
tion for the process of life.
By using chemically individual enzymes isolated from
living organisms one may produce, under laboratory condi-
tions and in isolation, separate biochemical reactions which
are links in the metabolic chain. This enables us to unravel
the complicated skein of chemical reactions which make up
metabolism, in which thousands of individual chemical
reactions are carried out ; to dismember metabolism into
its constituent stages ; to analyse not only the composition
of living bodies, but also the chemical processes which are
carried out in them and on which vital phenomena depend.
The great service of A. N. Bach (Bakh)^^ to biochemistry
was that, as early as the end of the nineteenth century, he
showed, in his study of the chemistry of respiration, for
example, that this phenomenon could not depend on the
ORIGIN OF THE FIRST ORGANISMS 375
effect of any single enzyme (e.g. laccase or some other oxidase)
but consisted of a chain of enzymic reactions which followed
one after the other and were co-ordinated in an orderly
fashion.
The same thing was established somewhat later for another
important vital phenomenon, that of fermentation.
L. Pasteur^^ in his day said that:
The chemical act of fermentation is essentially a phenomenon
associated with a vital activity, beginning and ending with that
activity ; there is no fermentation without simultaneous organ-
isation, development, multiplication of globules or the continua-
tion of life by globules which are already formed.
This supposition was refuted experimentally at the turn
of the century by E. Buchner.^^ By using a high pressure,
he expressed a juice fi'om yeast which did not contain any
living cells but which could nevertheless ferment sugar.
Buchner believed that his juice contained a specific enzyme,
' zymase ', which broke the sugar down to alcohol and
carbon dioxide by a single chemical act, just as, for example,
invertase breaks sucrose down into glucose and fructose.
However, the work which continued to be carried out for
many years afterwards by a whole constellation of the out-
standing biochemists of the first half of the present century,
in particular by S. Kostychev, A. Lebedev, C. Neuberg and
O. Meyerhof, showed that Buchner's juice contains, not one
single enzyme, but a whole complex of such catalysts.^® Each of
these accelerates its own specific reaction. All these reactions
are combined together to form a long chain of transformations
following one another successively in such a way that the end
product of the preceding reaction serves as the starting sub-
stance for a rigidly determinate succeeding reaction. Sugar,
on the one hand, and carbon dioxide and alcohol, on the
other, are merely the first and last links of this chain. The
reaction catalysed by each separate enzyme of the zymase
complex occupies its own essential place in the chain of trans-
formations, and forms an indispensable part of the chain as
a whole. By poisoning or blocking, one may inactivate selec-
tively any single enzyme of the zymase complex and thus
exclude the reaction which it catalyses from the general
376 THE FIRST ORGANISMS
sequence. The whole chain is then immediately disturbed
and fermentation ceases or is distorted.
By now most of the enzymes of the zymase complex have
been studied in great detail. Many of them have been isol-
ated and obtained in a pure state ; their chemical nature,
the character of their specific action and their dependence
on a number of physico-chemical conditions have been estab-
lished. Alongside this analytical work a number of extremely
interesting studies have been made, reproducing not merely
individual enzymic reactions, isolated links in the chain of
fermentation, but whole concatenations of these links, com-
binations of successive reactions catalysed by several enzymes
of the zymase complex. Thus it seems to be possible to
reproduce alcoholic fermentation artificially by the simul-
taneous action of all the enzymes and co-enzymes isolated
from Buchner's juice.
During the interaction of our original colloidal systems
with the medium surrounding them, and in the process of
their later development, there must have been formed within
them, not a single individual enzyme, but many specific
catalysts. Their simultaneous activity determined the occur-
rence of some particular chain of chemical reactions or a
whole network of reactions. On the nature of the organisa-
tion of this chain or network depended the greater or less
dynamic stability conferred by the network on the open
system. The selection of systems was based on this stability,
destroying those which had an ' unsuccessful ' combination
of reactions and preserving for further evolution only systems
with chains and networks which enabled them to survive for
a long while under conditions of constant interaction with the
external medium. It is obvious that it required a very pro-
longed and rigorous selection of a colossal variety of such
systems for there to arise, at last, a chain consisting of more
than 20 rationally concordant reactions such as take place in
alcoholic fermentation. In principle, however, the origin of
such a harmony between different catalytic reactions could
quite well have occurred during the process of directed
evolution and it seems that it must have come about at a
comparatively early stage in the origin and development of
life since the same basic collection of chains is common to,
ORIGIN OF THE FIRST ORGANISNfS 377
literally, all representatives of the living world which have
been studied in this respect.
However, the form of organisation of the chain of processes
on which extracellular fermentation is based is still relatively
primitive. It is only based on a certain qualitative composi-
tion of the mixtures of enzymes, i.e. the obligatory presence
in it of the whole collection of enzymes of the zymase com-
plex. The sequence of reactions in extracellular fermentation
simply depends on each intermediate product having its own
specific enzyme. Other transformations of the product are
excluded because, in the absence of the corresponding cata-
lyst, they would proceed incomparably more slowly than the
reaction which is accelerated by the enzyme. For this reason
the whole process of extracellular fermentation is of the
nature of a straight, unbranched chain. In the living cell
it is of great importance not only what enzymes are present
but also what are the quantitative relations between the
various catalysts acting there ; there must always be a certain
correspondence between their activities. This is specially
important when one and the same substrate can interact with
several of the enzymes present in the cell. As a result of this
the substrate is, in fact, altered in different directions. The
chain of reactions then becomes branched, and the relation-
ship between the rates at which reactions occur in the
different branches has sometimes been found to determine
whether or not some vital process can take place. A small
change in this relationship may cause not merely the cessation
of a process, but even the disruption of the whole system.
As an example of this we may cite the phenomenon of
respiration in the plant cell. It only takes place normally
when the process of oxidation of the chromogens into respira-
tory pigments by the oxygen of the air and the reverse process
of their reduction at the expense of the hydrogen of the
appropriate donors, correspond very closely with one another,
when their rates bear a precisely determined relationship to
each other. If, as happens on mechanical injury to the cell,
the rate of oxidation is increased disproportionately to that
of reduction, the respiratory pigment will not be able to be
reduced and will undergo further oxidation into a stable
378 THE FIRST ORGANISMS
brown pigment which cannot serve as a hydrogen acceptor.
In this way all the chromogen of the cell is very quickly
converted into an inactive state and the process of respiration
ceases as a result of the disturbance of the mechanism on
which it is based.^^
There is a great variety of substances in protoplasm by
means of which the accurate regulation of the catalytic activ-
ities of the enzyme complex is accomplished. In addition to
the new formation and irreversible destruction of the proto-
plasmic enzymes, there also occurs a widespread reverse
activation or inhibition of these catalysts. The protein nature
of enzymes not only determines their exceptional activity
and the specificity of their effects, it also determines their
great lability, their extreme sensitivity to different kinds of
physical and chemical factors. Any rough treatment will
cause the denaturation of proteins and their catalytic activity
will be irreversibly lost. But by treatment which does not
lead to denaturation the activities of enzymes may be altered
reversibly over a very wide range. In fact there is no physical
or chemical factor, no organic compound or inorganic salt,
which cannot affect the course of enzymic reactions in one
way or another. Any raising or lowering of the temperature,
any change in the acidity of the medium, its oxidation-
reduction potential, its salt content or its osmotic pressure,
interferes with the relationship between the rates of the
different enzymic reactions and thus changes their inter-
connections in the network of metabolism. Of great import-
ance in this connection is the development among the com-
ponents of protoplasm of various activators and inhibitors
with specific activities, which selectively speed up or slow
down any one or several enzymic reactions.^®
Owing to the action of all these supplementary chemical
mechanisms which are intimately associated with the physico-
chemical state prevailing at any given moment within the
protoplasm, very precise quantitative relationships are estab-
lished between the rates of the enzymic reactions. These
relationships may, however, vary greatly both as between
different organisms and even in a single cell at different
periods of its existence, and owing to the effects of different
external and internal conditions. This gives a form of organ-
ORIGIN OF THE FIRST ORGAiNISMS 379
isation which is very labile and adaptable, but at the same
time very efficient. The process of extracellular fermentation
is not associated with any protoplasmic structure ; the whole
process simply takes place in a solution of the enzymes of the
zymase complex. In the cells of contemporary organisms, on
the other hand, the spatial organisation of their protoplasm
exercises a great, and sometimes decisive, influence on the rate
and direction of the enzymic reactions on which its metabol-
ism is based. We now know that the enzymes of cells are
present, for the most part, in an associated state on proto-
plasmic surfaces and various cellular structures. ^^
The investigations carried out in the Institute of Bio-
chemistry of the Academy of Sciences of the U.S.S.R. (A.
Kursanov,^" N. Sisakyan, B. Rubin and A. I. Oparin*^) have
shown that the degi^ee of association of the enzymes with the
structures mentioned has a decisive effect not only in deter-
mining changes in the rates of the reactions catalysed by the
enzymes, but also in displacing the dynamic equilibrium of
the chemical processes towards a predominance of break-
down or synthesis. This, naturally, is of paramount import-
ance for the self-preservation and growth of the whole living
system. Phenomena of this sort cannot be explained on the
basis of the laws which have been established for closed
systems. As was shown in the previous chapter, however, in
open systems (as distinct from enclosed ones) a catalyst may
alter the stationary concentrations of the reacting substances,
i.e. it may displace the experimentally determined, dynamic
' equilibrium ' of the process.
This sort of influence of the protoplasmic structures on
the rate and direction of the enzymic reactions of the meta-
bolic network leads to a very intimate and critical connection
between the metabolism and the conditions of the external
medium. It very often happens that a factor which has a
very weak or hardly noticeable effect on the activity of isolated
enzymes will produce a radical displacement of the equi-
librium betw^een breakdown and synthesis, by altering the
associated power of the protein structures of protoplasm,
which are very sensitive in this respect.
According to contemporary cytological evidence^^ a very
considerable part of the cytoplasm, up to 50 per cent of its
380 THE FIRST ORGANISMS
weight, is composed of different formed structures, particles
of various sizes, for the most part mitochondria and micro-
somes. The mitochondria are rod-shaped formations visible
under the microscope. Their internal structure has been
fairly well studied both as to its morphology and its physical
chemistry. They have an envelope consisting of two pro-
tein layers with a lipid layer between them. The internal
core has a complicated structure and is also made up of
proteins and lipids. ^^ The microsomes are submicroscopic
and can only be discerned with the electron microscope.
Their structure has still only been very poorly studied.
According to J. D. Bernal** the arrangement of the molecules
of protein and nucleic acid in them is reminiscent of the
structure of globular virus particles.
Both the mitochondria and the microsomes are very rich
in lipids.*^ The mitochondria contain the iron-porphyrin
systems of the celP® while the bulk of the nucleic acid is
situated in the microsomes.*^ The mitochondria contain
large amounts of various enzymes. They seem to embody the
catalytic mechanism required by the cell for the processes
of oxidation and decomposition which lead to the liberation
of energy from the multifarious substrates entering the cell,
and also for the processes of transformation of this energy
into forms in which it can be used in synthetic processes and
for carrying out work in general. In particular, in the cells
of highly developed organisms capable of respiration, this
is carried out by means of the tricarboxylic cycle of Krebs
(a diagram of which is given in Fig. 40 on p. 466). This is
the most ^videspread system of oxidation of intermediate
products of the breakdown of various organic substrates.**
The Krebs cycle comprises a strictly ordered concatenation
of a large number of enzymic reactions, especially the hydra-
tion, dehydrogenation and decarboxylation of organic acids.
At particular points in the cycle there branch off side re-
actions leading to the formation of substances which can
serve as material for the synthetic processes of the cell. For
example, a-oxoglutaric acid is one of the links in the Krebs
cycle. It is formed from oxalosuccinic acid and later, in the
course of the transformations of the cycle, it is converted, by
oxidative decarboxylation, into succinic acid. This in its
ORIGIN OF THE FIRST ORGANISMS 381
turn is transformed into fumaric and then into malic acid,
etc. The a-oxoglutaric acid may, however, be transaminated
and part of it may leave the cycle by a side route and be
converted into glutamic acid which later serves as a ma-
terial for the synthesis of proteins. In this way part of the
a-oxoglutaric acid is always leaving the cycle irreversibly. In
just the same way other keto acids (pyruvic and oxaloacetic
acids) react with ammonia, i.e. are aminated directly,*® or
are transaminated^" to form alanine and aspartic acid respec-
tively. These are later transaminated to form other amino
acids.
The acetic acid arising in the cycle may later take part in
the formation of the citric acid of the cycle. ^^ Alternatively
it may leave the cycle to serve as the starting material for
the formation of fatty acids and other lipids. Oxaloacetic
acid and glycine are essential materials for the biosynthesis
of purine and pyrimidine bases, and glycine and succinic
acid for the construction of porphyrins. Thus, all these bio-
synthetic processes which form the basis for the synthesis of
living protoplasm are intimately associated with catabolism,
from which they obtain their structural starting materials.
At certain definite points on the cycle there is also libera-
tion of energy which is derived from high-energ\' bonds. ^^ The
energy of the substances in which these bonds were origin-
ally present is transferred to ATP in the mitochondrial
system. This, in its turn, activates substances taking a direct
part in synthetic reactions.
Owing to the extremely efficient spatial disposition of the
enzymes and coenzymes of the respiratory and energetic
complex, their orderly assembly in the mitochondria, the
cell achieves a maximal effect in the oxidation of substrates
and the transformation of energy. The energy made avail-
able in this way is intimately associated with the formation
of fragments of molecules which serve as materials for the
synthesis of the substances of which the cell is made.^^ The
intensity of the oxidative processes in the mitochondria is,
therefore, regulated by factors responsible for maintaining
the balance between the liberation of energy and the supply
of materials required for synthesis.
The direct synthesis of proteins from amino acids takes
382 THE FIRST ORGANISMS
place in the nucleic acid-rich microsomes, as has been shown
by experiments using labelled atoms/* The energy needed
for this reaction is made available in the mitochondria. It
has been supposed that it enters the microsomes in the form
of high-energy bonds of activated peptides containing the
y-glutamyl group. ^^ The microsomes themselves seem to be
f^uc/eus
f/uc/eo/us
60/gifiM
-Microsomes
,''0 •T°\ •
' • . - o °y • „
Af/toc/iondnot
ZLL
Mijfi- energy -ionds 'sc/ife'
precursors of pro terns, lipids
snd Mrdofigorifes
Fig. 35. Diagram of the formation of cytoplasmic
particles and their interaction with other elements
(after Lindberg and Ernster).
formed from proteins, ribonucleic acids synthesised under
the control of the nucleus and lipids which are formed in the
mitochondria and stored in the Golgi apparatus.^®
We give a diagram of these interactions of the formed
elements of the cell as it is given by Lindberg and Ernster'*^
(Fig. 35)-
The form of organisation of protoplasm which we have
described is extremely efficient. With an organisation of this
sort, owing to its definite spatial localisation, complete in-
dependent blocks of well ' assembled ' enzymes interact in
the performance of certain vital functions. Thus we have
here a well-organised ' division of labour ' between the
various structures of the cell operating to achieve the maxi-
mum effect in the transformation of energy and the synthesis
of living material.
Naturally this sort of organisation could only arise as a
result of the prolonged development of living matter and it
ORIGIN OF THE FIRST ORGANISMS 383
is, therefore, only to be found in organisms which have
already reached a comparatively high level on the evolution-
ary ladder. Even in the comparatively poorly organised
living things of the present time it is far more primitive.
It must be supposed that the organisation of the primaeval
organisms was even more primitive, although such a form
of spatial localisation of the various enzymes and the reactions
which they catalyse must have existed even at this stage of
evolution.
Even the reactions of alcoholic fermentation take place
far less harmoniously in Buchner's juice, where the spatial
localisation of the enzymes is largely destroyed, than in yeasts
or bacteria. But, most important of all, in Buchner's juice
the process of fermentation follows, as it were, a lone trail.
Here none of the energy liberated during the breakdoAvn of
sucrose to carbonic acid and alcohol is used rationally in
any way. In the living cell, on the other hand, owing to
the strict co-ordination of the chemical reactions, this energy
participates to a greater or lesser degree in the process of
synthesis of living material.
Of course, it is still very hard to answer the question as
to what was the spatial organisation of the earliest living
things. Considerable light might be shed on this problem
by a comparative study of this organisation among the more
primitive contemporary organisms. The study of multiple
coacervates might also give some indication of the possible
means whereby the simplest internal structure of the original
colloid systems could have arisen. In multiple coacervates
formed of several components there is an internal separation
of the individual components in space, in that small droplets
of one coacervate arise within the drops of another. For
example, on mixing solutions of gelatin, gum arabic and
sodium nucleate, drops are formed, composed of gelatin and
gum arabic. Within these drops there are formed small
droplets containing gelatin and nucleic acid." This can
easily be demonstrated by selective staining or by the use
of the ultraviolet microscope. ^^ Various substances and cata-
lysts may become localised on the internal surfaces which
are formed in this way.
In summarising what has been said one must emphasise
384 THE FIRST ORGANISMS
the extreme complexity and diversity of the factors which
determine the organisation of contemporary living bodies in
time, the causes on which the structure of the network of
chemical transformations of their metabolism depends. The
formation of this network was determined by the chemical
properties of the compounds of which living bodies were
composed. The great diversity of these compounds and their
extreme chemical reactivity carried with them the possibility
of numerous chemical transformations and unlimited com-
binations of the compounds. But, in this extremely wide
field of chemical possibilities the process of directed evolution,
by the gradually increasing organisation of living systems,
led to the emergence of ever more clearly defined pathways
of biochemical processes which formed a more and more
efficient network of metabolic reactions.
In contemporary organisms this network has reached a
very high efficiency. Its organisation is determined, as we
have seen, by a whole complex of concordant factors: the
presence of a particular collection of enzymes, their quantita-
tive relationships, the physico-chemical conditions prevailing
in the protoplasm, its colloidal properties and, finally, its
structure, the definite localisation of chemically and bio-
logically active compounds and the irreversible nature of the
biochemical processes. The original systems, and even the
earliest living things, did not have to the full such a compli-
cated and efficient form of organisation. However, both before
and after the emergence of life, there took place a directed
evolution, not of isolated factors or parts of the system, but
of the metabolic network as a whole, leading towards its
improvement. In the course of this evolution there con-
tinually arose new pathways, some of which became pre-
dominant in metabolism at the same time as old pathways
disappeared or merely remained in reserve. During all these
changes, however, there was always maintained a network
which, to some extent, provided for constant self-preservation
and self-reproduction of the system as a whole. The improve-
ment of the metabolic network only implied the more and
more rational performance of this task under more and more
diverse and varying environmental conditions.
As the metabolic network improved so there arose and
ORIGIN OF THE FIRST ORGANISMS 385
developed those properties of the system which may be
regarded as the characteristic features of life, which are
fundamental to the organisation of this form of the motion
of matter.
The interaction with the external medium of such systems
as coacervate droplets, which have no organised network of
chemical reactions, can only be based on the permeability
of surface membranes or the adsorptive properties of colloids.
In this case, however, the entry of substances into the system
by such means soon ceases and the system enters into equi-
librium. Only when the substances entering the system in
one ^vay or another can be changed and accumulated within
the system in the form of some particular compounds, or cast
out into the surrounding medium as breakdown products,
can the phenomenon of interaction between the system and
its environment continue for a long time. This must have
occurred when coacervate drops were transformed into open
systems at a comparatively early stage in the evolution of the
original colloidal formations. But, in this case, the entry
of substances into the system or their expulsion into the
external medium must already have ceased to depend on
the simple laws of permeability and adsorption and have
depended on the state of development of the organisation of
the network of reactions into which the substances derived
from the external medium entered, or in which the break-
down products which were expelled were formed.
It is precisely this sort of interaction with the external
medium, though in a considerably more highly developed
form, which is characteristic of all contemporary living
things. According to the evidence of contemporary cytology
and cellular physiology,^' the entry of substances from the
environment into the cell is not a passive process determined
by the greater or lesser mobility of these substances through
a hypothetical semi-permeable membrane, or by their selec-
tive adsorption on protoplasmic surfaces, as had earlier been
supposed. This entry is brought about by the active participa-
tion of the whole cellular metabolism. It occurs because
the substances which enter are drawn into the network of
metabolic reactions. For this reason any disturbance of meta-
bolism, such as a decrease in cellular respiration, has an
25
386 THE FIRST ORGANISMS
immediate and decisive effect on the entry of substances into
the cell.
In an analogous way the characteristic features of cellular
energetics depend on the high degree of organisation of the
metabolism of protoplasm.^" In the engines which are widely
used in industrial processes, the chemical energy which is
liberated by burning the fuel is usually first converted into
heat and only later transformed into other forms of energy.
In protoplasm the energy liberated by the decomposition of
organic substances (in the process of fermentation or by their
oxidation during respiration) is converted directly into the
forms of energy required for life. Owing to this an extremely
high coefficient of utilisation of energy is achieved in living
bodies such as is not approached by our technology. In the
engines of the present time this coefficient reaches, at best,
40 per cent, and this requires considerable temperature
differences, of the order of hundreds of degrees. If the trans-
formation took place in living bodies in the same way as in
heat engines, then, at the temperature differences which are
possible for organisms, the coefficient of energy utilisation
would only be a fraction of 1 per cent. Nevertheless it in fact
reaches 50 per cent or even more. This is explained by the
fact that the breakdown and oxidation of sugar or other
energy-yielding material does not take place as an isolated
process in the living cell, but through a series of separate
reactions which are strictly co-ordinated in time and which
form the chains and cycles which constitute metabolism. The
chain of alcoholic fermentation and the oxidative cycle of
Krebs may serve as examples.
It must be pointed out that if the oxidation of organic mole-
cules were to take place all at once in protoplasm, the living
body would not be able to make rational use of the energy
thus liberated. The oxidation of only one gram-molecule of
sugar to carbonic acid and water liberates about 700 kcal.
The instantaneous release of this amount of energy would
be associated with a sharp rise of temperature, the denatura-
tion of proteins and the destruction of protoplasm. The
energetic effect achieved by protoplasm at ordinary low tem-
peratures depends on the fact that, in the process of biological
ORIGIN OF THE FIRST ORGANISMS 387
oxidation or degradation of sugar, this substance is not con-
verted into its end products all at once, but by gradual stages.
This sort of organisation not only gives rise to the possi-
bility of overcoming the high barrier of the energy of activa-
tion of the reaction of the oxidation of sugar by atmospheric
oxygen at ordinary temperatures ; it also allows the living
cell to make rational use of the energy, which is not liberated
all at once but gradually in separate small portions. We have
already seen from the example of the Krebs cycle that this is
^vhat actually takes place. At definite points on this cycle
energy is liberated, whereupon it is immediately taken up
to form ATP, or some other compound with high-energy
bonds, which may be used for carrying out syntheses or for
performing work necessary for life."
The more highly organised the metabolism and the better
the co-ordination between the separate reactions of which it
is made up, the higher will be the coefficient of useful work.
Direct observations on various representatives of the living
world show that in poorly organised living things, standing
at the bottom of the evolutionary scale, the reactions of the
energetic network are not always strictly co-ordinated. A
considerable amount of the energy liberated in them is there-
fore dispersed aimlessly and cannot be used for vital processes,
in particular for the formation of new living material and
the growth of cells. *^ When, on the contrary, the rates of
the reactions are strictly co-ordinated, when they are, so to
speak, accurately adjusted to one another, this w^aste of energy
is cut down substantially. In such a case a relatively small
access of the organic materials serving as the source of
nourishment leads to considerable growth of the living thing.
This may be seen in moulds, for example, where the
metabolism is very highly organised. H. Tamiya" in par-
ticular obtained the following data for Aspergillus oryzae :
for the formation of i g. of mycelium the mould assimilated
1 467 g. of glucose. The efficiency of the utilisation of energy
was thus ^ :^, — z- x 100= 87 per cent. This effici-
1-467 X 3-76 kcal ' ^
ency is exceptionally high and other authors®* assign a loAver
percentage value to it, but even they obtain very high values
388 THE FIRST ORGANISMS
in moulds. In some bacteria, on the other hand, this efficiency
is incomparably less and this is associated with incomplete
co-ordination of the various links of their chains of energy
metabolism.
The energy metabolism of the primaeval organisms must
certainly have been at a still lower level of development. The
commencement of this metabolism must, however, have
taken place in the very early stages of the evolution of our
original systems as the only easily mobilised sources of energy
available to them were organic compounds which entered
the system from outside. However, if the energy contained
in these substances was to be released, they had to be broken
down in some way. At first this breaking down took many
forms and followed various paths and its efficiency must
therefore have been very low.
Later, however, selection led to the formation of several
standard paths which formed the basis of the energy exchange
of all living things without exception. The earliest reactions
in the process of glycolysis, in particular, seem to constitute
such paths. They have been found in all organisms where
they have been looked for.
As we saw above, the definite organisation of the network
of metabolic reactions also forms the basis for the synthesis
of all the substances formed in living matter. This may be
demonstrated above all by the origin of the property which
first Pasteur^^ and then Vernadskii®® considered to be one
of the most characteristic features of life, namely, the asym-
metry of protoplasm.
What is the cause of this asymmetry? Why is there only
formed in living protoplasm one particular optical configura-
tion of amino acids and other similar compounds?
In Chapter V we indicated that in the original solution of
organic substances the action of circularly polarised light or
selective synthesis on the surfaces of quartz crystals could
have led to the appearance of a certain dissymmetry, some
predominance of the dextro or laevo antipodes of particular
compounds. This original asymmetry may have formed the
basis for the asymmetry of all later organic formations.
It is generally supposed that one molecule with a particular
optical configuration gave rise to another exactly similar
ORIGIN OF THE FIRST ORGANISMS 389
molecule, ' multiplied ' so to speak more and more, so that
there was a steady increase on the surface of the Earth in
the amount of the compounds ^vhich belonged to the series
of optical isomers in question. A detailed examination of
the subject shows, however, that the matter is considerably
more complicated.
W. Kuhn^^ in his day undertook a detailed analysis of all
the evidence then available concerning asymmetric synthesis.
He showed, in the first place, that a racemic mixture is
thermodynamically more stable than its separate optically
active components because the free energy is less in the
racemic mixture. Any mixture of optically active substances
will, therefore, tend to racemise and lose its optical activity.
In any synthesis mediated by an asymmetric catalyst (e.g.
an enzyme) at first only one optical antipode will be formed
quickly. However, the other antipode is formed too, but
in an amount which is as many times smaller than that of
the first as the rate of the synthesis in the presence of the
catalyst is greater than the rate without the catalyst. This
will lead to the appearance of a certain asymmetry, a certain
inequality between the amounts of the dextro and laei^o anti-
podes. But as a true catalyst increases the rate of a reaction
and of the reverse reaction, after equilibrium has been
reached some of the product of the synthesis will be converted
into the starting substance giving rise, though very slowly,
to fresh amounts of the antipode which is synthesised without
the catalyst. Thus the whole system will tend towards the
racemic state and the optical activity which arose as a result
of the action of the asymmetric catalyst will gradually get
weaker as may, in fact, be demonstrated by experiment.®*
Thus the asymmetry which arose in an enclosed system
owing to the activity of any isolated reaction must have been
a temporary phenomenon and could not have served as a
basis for the formation of the very complete and constant
asvmmetry of protoplasm.
The continual formation of only one optical antipode can
only occur in open systems on the basis of a definitely
organised network of reactions, the rates of which are very
accurately related to one another. Under such conditions,
when there is a definite sequence of processes, racemisation
390 THE FIRST ORGANISMS
or the appearance of the opposite antipode may be avoided
altogether and the system may retain its asymmetry indefin-
itely.''
Thus the asymmetry of protoplasm is due to its definite
organisation in time, the co-ordination of the reactions occur-
ring in it. This co-ordination certainly did not arise by chance.
It was enabled to arise by selection of the original systems,
for, according to W. H. Mills, ^^ everything else being equal,
reactions proceed at a significantly slower rate in racemic
mixtures than in optically active mixtures. Systems made
up of asymmetric material must therefore have been more
effective in the struggle for existence than their competitors
made up of racemic mixtures.
Systems, in which a definite co-ordination of reactions had
led to the formation of asymmetry, carried out their syntheses
more quickly than otherwise identical systems based on
racemic mixtures. The growth of the former must therefore
have been significantly faster and their dynamic stability
must have been greater. As a result of all this the action of
selection must have tended to increase the asymmetry of
the substances entering into the composition of our original
colloidal systems from the first stages of their evolution. In
contemporary protoplasm this asymmetry has reached a very
high level ; there is an extremely high degree of optical purity
which can only be present as a result of a very close co-
ordination of the rates of the reactions contributing to the
synthesis of the substances in question.''^
In order to renew and preserve themselves continually in
a state of uninterrupted interaction with the external
medium, our original systems could extract the ingredients
which they needed ready-made from the medium, sometimes
in the form of very complicated organic molecules. However,
even at the earliest stages of the evolution of our original
systems, the substances entering them must have undergone
some sort of chemical transformation, otherwise the pro-
perties which characterise open systems could not have arisen.
As we saw above, this did not involve any direct ' multiplica-
tion ' of the individual molecules, they could not ' reproduce
themselves ' directly. What did occur was only a more or
less constantly repeated formation of new material based on
ORIGIN OF THE FIRST ORGANISMS 39 1
chemical reactions taking place in a certain sequence. Thus,
for the progressive evolution of our original systems the
important thing was not the chance entry or development
of any particular compound, but the appearance of a definite
co-ordination of the reactions which provide the constant
synthesis of this compound in the system in continuous inter-
action with the external medium.
The more closely the chemical substances entering it from
the external medium resembled ingredients of the system
itself, the less complicated were the chains of reactions leading
to its synthesis and the simpler was the metabolic organisa-
tion. However, the system Avas correspondingly more depen-
dent on the constancy of the external medium and on its
high content of complicated organic compounds.
Clearly the selection of our original systems and the emerg-
ence of the first organisms from among them must have been
directed towards a lessening of this dependence and the
formation of networks of synthetic reactions by which the
complicated ingredients of the system could be synthesised
unerringly from the somewhat diverse compounds ^vhich
entered it from the external medium. For this purpose the
compounds in question had to be ' standardised ', that is to
say, broken down to relatively simple and uniform fragments
from which any specific ingredients of the system could be
built up by standard methods, though using complicated
chains of transformations with many links.
We do, in fact, find such a form of organisation in the
constructive metabolism of contemporary organisms. In
them, as we have pointed out several times, very simple
compounds of low molecular weight such as oxalic acid,
glycine, succinic acid, keto acids, etc., serve as starting points
for the synthesis of proteins, nucleic acids, lipids, porphyrins
and the other complicated ingredients of protoplasm. These
simple compounds arise as fragments split off in the course
of the destructive metabolism of the sugars and other sub-
stances which enter the cell from its surrounding medium
and serve as its nutrients. In the course of this destructive
metabolism the energ\^ needed for synthesis is liberated and
stored in ATP and other compounds with high-energy bonds.
We have already explained this with reference to glycolysis
392 THE FIRST ORGANISMS
and the tricarboxylic acid cycle of Krebs. These examples
show that the biosynthetic processes, which form the basis
for the formation of the living material of organisms, are
intimately associated with destructive metabolism, from
which they obtain their original structural materials and the
energy needed for synthesis.
The route by which the fragments under discussion are
built up into proteins, nucleic acids or porphyrins is, of
course, very complicated and consists of a series of successive
reactions. Such syntheses can, therefore, only take place by
means of a very precise and absolutely constant co-ordination
of these successive reactions, by means of a very highly devel-
oped organisation of the metabolic network. This was also
essential for the appearance of the most characteristic feature
of life, the capacity for self-reproduction.
Thus, we can now already give an indication, though still
only a very rough and speculative one, of the actual course
of development leading from the initial systems to the
simplest organisms during the emergence of life on our
planet. This development involved successive improvements
in the networks of reactions within individual colloidal sys-
tems which were reacting with the external environment.
Owing to continual changes in these systems, within the limits
of their dynamic stability, they underwent the following
transformations. First there was the formation of individual
catalysts of great reactivity and specificity. Later the activity
of these catalysts was co-ordinated and there arose the whole
chains and cycles of enzymic reactions which form the basis
for the separate departments of metabolism. Still later came
the spatial organisation of the system and the localisation of
processes and the rationalisation of the interacting energic
and structural branches of metabolism. This guaranteed,
within limits, the continual self-preservation and self-
reproduction of living systems.
The nature of this organisation may, naturally, vary within
limits in different representatives of the living world, but
it is always an expression of the degree of integration attained
by the organism in the course of its evolutionary develop-
ment. A comparative study of contemporary living things
will enable us to form an opinion as to the course of the
BIBLIOGRAPHY 393
successive integration of this remarkable form of the motion
of matter which came into being at some time on the Earth.
BIBLIOGRAPHY TO CHAPTER VIII
1. (VI. 6).
2. A. S. KoNiKovA and M. G. Kritsman. Voprosy Filosofii, 1934,
no. 1, p. 210.
R. Brunish and J. M. Luck. /. hiol. Chem., igy, 86g (1952).
3. M. G. Kritsman, A. S. Konikova and Ts. D. Osipenko.
Biokhimiya, ly, 488 (1952).
4. T. E. Pavlovskaya, M. S. Volkova and A. G. Pasynskii.
Doklady Akad. Nauk S.S.S.R., loi, 723 (1955)-
5. (VI. 6).
6. (III. 75).
7. (VII. 87).
8. (VII. 71).
9. A. G. Pasynskii. Uspekhi sovremenjio). Biologii (in Press).
10. N. Kol'tsov. Organizatsiya kletki. Moscow and Leningrad
(Biomedgiz), 1936.
11. H. G. Wood, R. W. Brown and C. H. Werkman. Arch.
Biochem., 6, 243 (1945)-
12. G. Ehrensvard. Ajin. Rev. Biochem., 24, 275 (1955)-
13. R. Robinson. Nature, Lond., i^y, 172 (1936).
14. R. ScoTT-MoNCRiEFF. Ergebu. Enzymforsch., 8, 277 (1939).
15. V. I. NiLov. Izvest. Akad. Nauk S.S.S.R. {Ser. bioL), 6, 1709
(1937)-
K. Paech. Biochemie und Physiologic der sekunddren Pflan-
zejistofje. Berlin, 1950.
16. A. KuRSANOv. y-oe Bakhovskoe chtenie. Moscow (Izd. AN
SSSR), 1952.
17. K. MoTHES. Ann. Rev. Plant Physiol., 6, 393 (1955).
18. W. H. Sebrell and R. S. Harris (ed.). The Vitamins. New
York, 1954.
19. T. N. GoDNEV and A. A. Shlyk. Priroda, 19^^, no. 5, p. 48.
20. D. W. WooLLEY. A study of antimetabolites. New York,
1952-
21. (VI. 188).
Z2. (VI. 209).
23. A. I. Oparin, T. N. Evreinova, T. A. Shubert and M. N.
Nestyuk. Doklady Akad. Nauk S.S.S.R., J04, 581
(1955)-
394 THE FIRST ORGANISMS
24. K. Oppenheimer. Die Fermente und ihre Wirkungeji. Leip-
zig> 1925-1929-
F. F. NoRD and R. Weidenhagen (ed.). Hajidbuch der En-
zymologie. Leipzig, 1940.
25. J. H. Northrop, M. Kunitz and R. M. Herriott. Crystal-
lijie enzymes (2nd edn.). New York, 1948.
J. B. Sumner and G. F. Somers. Chemistry and methods of
enzymes (2nd edn.). New York, 1947.
26. E. A. MoELWYN-HuGHES in The Enzymes (ed. J. B. Sumner
and K. Myrbiick). Vol. 1, Part 1, p. 28. New York,
1950.
27. V. L. Kretovich, a. a. Bundel', S. S. Melik-Sarkisyan and
K. M. Stepanovich. Biokhimiya, ip, 208 (1954).
28. K. Zeile and H. Hellstrom. Hoppe-Seyl. Z., 1^2, 171 (1930).
K. Zeile. Hoppe-Seyl. Z., ip^, 39 (1931).
29. P. V. Afanas'ev. Biokhimiya, 14, 259 (1949).
B. Chance. Advanc. Enzymol., 12, 153 (1951).
30. S. Spiegelman. Co7ifere7ices et Rapports, ^-eme Congres
international de Biochimie, Bruxelles, 1-6 Aout 19^5,
p. 185. Liege, 1956.
31. W. Langenbeck. (VI. 66) ; Advanc. Enzymol., 14, 163 (1953).
32. K. Lohmann and P. Schuster. Biochem. Z., 294, 188 (1937).
33. A. N. Bakh. /. Kuss. phys.-chem. Soc. (Chem. section), 2p
(div. 1), 373 (1897 ) ; 44 (div. 2), 1 (1912).
34. L. Pasteur. C.R. Acad. Sci., Paris, 80, 452 (1875).
35. E. Buchner, H. Buchner and M. Hahn. Die Zymasegdrung.
Munich, 1903.
E. Buchner and R. Rapp. Ber. dtsch. chem. Ges., ^2, 127
(1899)-
36. S. Kostychev. Izbrannye trudy po fiziologii i biokhimii
mikroorganizmov. Moscow (Izd. AN SSSR), 1956.
A. Lebedev. Khimicheskie issledovaniya nad vnekletochnym
spirtovym brozheniem. Novocherkassk (Tip. Mamon-
tova), 1913.
F. F. NoRD in Handbuch der Enzymologie (ed. F. F. Nord
and R. Weidenhagen), p. 968. Leipzig, 1940.
37. A. Oparin. Biochem. Z., 182, 155 (1927).
38. T. Bersin in Handbuch der Etizymologie (ed. F. F. Nord
and R. Weidenhagen), p. 154. Leipzig, 1940.
(VL 65).
39. N. M. Sisakyan. Fermentativnaya aktivnost' protoplazmen-
nykh struktur. Moscow (Izd. AN SSSR), 1951.
BIBLIOGRAPHY 395
40. A. KuRSANOv. Obratimoe deistvie ferment ovv zhivol rastiteV-
1101 klelke. Moscow (Izd. AN SSSR), 1940.
41. A. I. Oparln. Uspekhi Khim., ^, 200 (1934) ; Ergehn. Enzym-
forsch., 3, 57 (1934) ; Bull. Soc. Chim. biol., Paris,
52,306 (1950); (VI. 153).
42. (VI. 158).
43. H. U. Zollinger. Amer. J. Path., 2^, 545 (1948).
F. SjosTRAND. Nature, Lorid., 168, 646 (1951).
K. W. Clelan'd. Nature, LoJid., ijo, 497 (1952).
44. J. D. Berxal. Lectures to Moscow State University, Sep-
tember 1956.
45. A.Claude. J. exp. Med., 84,^1 (1946).
46. ^V. C. Schneider and G. H. Hogeboom. Cancer Res., 11, 1
(1951)-
47. A. Claude. /. exp. Med., 80, 19 (1944).
48. D. E. Green. Symposium sur le cycle tricarboxylique. 2-eme
Congres international de Biochimie, p. 5. Paris, 1952.
49. V. L. Kreto\ich and A. A. Bundel'. Doklady Akad. Nauk
S.S.S.R.,^9, 1595 (1948).
V. L. Kretovich, a. a. Bundel' and K. B. Aseeva. Doklady
Akad. Nauk S.S.S.R., 80, 225 (1951)-
50. A. BR.\UNSHTEiN. Biokhimiya aminokislotnogo obmena. Mos-
cow (Izd. AMN SSSR), 1949 ; 12-oe Bakhovskoe
chtenie. Moscow (Izd. AN SSSR), 1956.
51. S. OcHOA. Symposium sur le cycle tricarboxylique. 2-eme
Congres international de Biochimie, p. 73. Paris,
1952-
52. B. Chance and L. Smith. Ann. Rev. Biochem., 21, 687 (1952).
53. F. Lipmann, M. E. Jones and S. Black. Symposium sur
le cycle tricarboxylique. 2-eme Congres international
de Biochimie, p. 55. Paris, 1952.
54. J. Brachet. £nz}'mo/ogm, 70, 87 (1941).
P. C. Zamecntk. Ann. Rev. Biochem., 21, 411 (1952).
P. SiEKEViTZ. 7. biol. Chem., 795, 549 (1952).
55. J. E. Snoke and F. Rothman. Fed. Proc, 10, 249 (1951)-
56. C. Vendrely. Arch. Anat., Strasbourg, 55, 113 (1950).
57- (VII. 35)-
58. T. N. EvREiNOVA. Biofizika, i, 167 (1956).
59. (VII. 41); (VII. 51).
60. (VII. 82).
61. H. A. Krebs. Symposium sur le cycle tricarboxylique. 2-eme
Congres international de Biochimie, p. 42. Paris,
1952-
396 THE FIRST ORGANISMS
62. (IV. 35).
63. H. Tamiya. Acta phytochim. Tokyo, 6, 265 (1932) ; '], 27
(1933)-
64. J.W.Foster. Chemical activities of fungi. New York, 1949.
65. (V. 151).
66. (II. 9).
67. (V. 159).
68. (V. 167).
69. P. D. Ritchie. Asymmetric synthesis and asymmetric induc-
tion. Oxford, 1933.
70. W.H.Mills. J. Soc. chem. Ind., ^i^'j^o (ig^z).
71. (V. 143).
CHAPTER IX
THE FURTHER EVOLUTION OF
THE FIRST ORGANISMS
The concept of comparative
biochemistry.
Strictly speaking, the origin of the first organisms should
conclude an exposition of the origin of life on the Earth.
When this had taken place matter entered into a new, bio-
logical stage of its development. There began the evolution
of living things from the most primitive original organisms
to the highly-developed plants and animals which now live
on our planet.
Careful study of this already purely biological evolution
may, however, be very helpful towards understanding the
actual origin of life, the way in which it came into being.
At the present time we cannot observe this process directly
in nature because all the intermediate links, the more primi-
tive and incomplete forms of organisation of living matter,
would appear to have been destroyed long ago, swept from
the face of the Earth by natural selection. However, a study
of the organisation of protoplasm in contemporary organisms
at different levels on the evolutionary scale provides us with
some objective evidence as to the nature of the earliest forms
in which life existed on the Earth.
Especially valuable in this respect is the study of metabol-
ism, that ordered series of biochemical processes which forms
the basis of the organisation of protoplasm in time and in
space. As we saw above, metabolism occurred even in the
very earliest organisms, but was altered and brought to a
higher degree of integration dining the process of their
evolutionary development. This involved the repeated appear-
ance of new conjunctions of biochemical reactions and new
chemical mechanisms within the protoplasm on which these
reactions depended. These enabled organisms to make better
397
398 FURTHER EVOLUTION
use of a wider variety of sources of energy and starting
materials required for life, for constant self-renewal and self-
reproduction. A comparative study of metabolism in primi-
tive and highly-developed organisms enables us to understand
the characteristic features of the organisation of chemical
processes which is the very foundation of life and which arose
by the same process which brought life into being.
As a comparative study of the structure of the organs of
individual animals enables an anatomist to piece together
a picture of their evolutionary development and allows us to
look into their remote past, so also a comparative study of
the metabolism of different organisms enables a biochemist
to approach the actual origin of life and to understand the
more primitive forms of its organisation.
Comparative biochemistry, in this sense, is still a very
young subject. It is only very recently that any significant
factual material has been collected to enable us to compare
the organisation of metabolism, its individual links, in
different representatives of the living world. Even now this
material is far from comprehensive and permits few general-
isations.
The great obstacle to the interpretation of the evidence of
comparative biochemistry is that the evolution of metabolism
is not a single process proceeding in a straight line. It follows
paths which are winding and confusing, very varied, often
intersecting and sometimes even reversing themselves.
However, a comparative study of the chemistry of pro-
tein synthesis, fermentation, respiration, chemo- and photo-
synthesis and other vital processes in different micro- and
macro-organisms shows that the new concatenations of bio-
chemical reactions which arise during evolution do not by
any means always supplant the old metabolic chains of meta-
bolism but merely supplement them, forming, as it were,
an auxiliary ' superstructure ' on the existing chemical
mechanisms of the protoplasm. In certain sections of meta-
bolism we may even sometimes see two parallel chains of
chemical transformations, of which the newer one is used
extensively in metabolism while the older one is, essentially,
only a reserve. It is, nevertheless, preserved intact, and when
FIRST HETEROTROPHS AND ANAEROBES 399
the conditions of existence are radically changed, the organ-
ism possessing such a chain can easily fall back on it.
This may, to some extent, serve as a guiding thread in the
complicated labyrinth of intersecting paths of metabolic
evolution. If we establish that a given system of biochemical
reactions is peculiar to the metabolism of a definite, more or
less well-defined gi'oup of organisms and is absent from all
other living things ; and if it only forms an accessory super-
structure in the metabolism of these organisms while the
chemical changes in which it participates are based on a more
generally-used catalytic mechanism ; and if, finally, under
certain conditions, this superstructure may be displaced or
superseded by the other mechanism ; then we are justified
in regarding such a set of reactions as a supplementary system
of metabolism which only arose at a later stage in the phylo-
genetic development of the organisms in question.
In contrast to this, in the study of the metabolism of
different sorts of organism we also meet with chemical systems
and catalytic mechanisms which seem to be extremely widely
distributed, to be present in all groups of living things
without exception, in protozoa, bacteria, algae, fungi, terres-
trial green plants and all the various categories of the animal
world. We are justified in considering such metabolic systems
as being of more ancient origin and as forming the very basis
of the organisation of living things.
The first living things — heterotrophs
and anaerobes.
Working in this way, trying to detect the points of similar-
ity among the tremendous variety of metabolic systems in
diff^erent organisms, the features of organisation which are
most w^idespread among all living things and which are there-
fore most ancient, we can put forward two cardinal theses.
In the first place, the metabolism of all living things is
based on the ability to use ready-made organic substances
as the starting materials for the construction of proteins,
nucleic acids and other components of protoplasm and also
as the immediate source of energy for these biosyntheses.
This ability is characteristic even of those organisms which
400 FURTHER EVOLUTION
have a chemical organisation enabling them to synthesise
organic compounds directly from carbon dioxide, water and
mineral salts and which can use such sources of energy as
sunlight and the oxidation of inorganic substances for the
purpose.
In the second place, the general method whereby all
organisms obtain energy from organic substances is by de-
composing them anaerobically. Many contemporary living
things have chemical mechanisms which enable them to
use the energy of organic substances far more fully and
efficiently by their complete oxidation by the oxygen of the
air in the process of respiration, but their metabolism is also
based on the same system of anaerobic decomposition which
is common to all organisms.
These generalisations have been established by means of a
comparative study of the metabolism of all sorts of contempo-
rary organisms. They provide a solid confirmation of the
hypothesis concerning the way in which the first living things
arose which we propounded in the previous chapters. The
taking in of organic substances dissolved in the surrounding
aqueous medium and their transformation into parts of its
own body is, obviously, the absolutely indispensable form of
metabolism in a living body which arises by the incorpora-
tion of polymeric organic compounds into multimolecular
systems. Even the coacervate drops which were first formed
in the waters of the primaeval ocean must have been able to
incorporate in themselves the organic substances of the sur-
rounding medium. All their subsequent evolution was based
on the natural selection of those systems which could assimi-
late these substances most quickly and efficiently.
The first organisms which arose in this way needed ready-
made organic substances primarily for keeping the balance
of their metabolism constantly positive and for the fastest
possible synthesis of the proteins, nucleic acids, enzymes and
other components of the living system. The more primitive
the organisation of such a system the greater the demands
it will make on the starting structural material and the more
similar this material must be to the components of the living
body which are to be synthesised from it. Many contempo-
rary organisms can synthesise quite complicated organic
FIRST HETEROTROPHS AND ANAEROBES 4OI
compounds from very small original molecules ; the carbon
skeletons of the various amino acids, including the aromatic
and heterocyclic ones, are built up by contemporary organ-
isms from acetic acid and other simple breakdown products of
monosaccharides. ^
Ammonia, oxaloacetic acid, glycine and formyl residues
serve as the material for the synthesis of purine and pyrimi-
dine bases, ^ while glycine and succinic acids serve for por-
phyrins,^ etc. However, as we have mentioned above, such
syntheses require the presence of a very highly developed
organisation of protoplasm. If the very simple starting ma-
terials are to be transformed into complicated organic com-
pounds the biosynthesis must occur by means of a long series
of intermediate stages. These must be very well co-ordinated
in time so that the intermediate product which is formed
as a result of one reaction will be completely transformed
by the next reaction into a new and more complicated
compound. The greater the number of links in a metabolic
chain the more its realisation will depend on specific enzymes
or even on whole complexes of enzymes, and the more accurate
must be the co-ordination of the velocities of the separate
reactions, both those whereby the small molecules are con-
verted into larger formations and those supplying the energy
required for these syntheses.
In 1945 N. H. Horowitz,* on the basis of studies of the
fungus Neurospora, gave a very interesting schematic accoimt
of the way in which the synthetic abilities of the primary
living things became more complicated during their evolu-
tion, though this scheme still requires some biochemical
particularisation. The gist of Horo^vitz' scheme is as follo^vs :
Let us assume that some very simple organism required the
rather complicated compound A for its vital processes. If
this compound were present, ready-made, in the surroimding
medium the organism could assimilate it directly without
possessing any chemical ability to synthesise the substance.
However, if there should arise a deficiency of the material
in the outside medium, or if it should vanish altogether, the
only organisms which could continue to exist would be
those in which there had somehow arisen a new chemical
mechanism enabling them to synthesise substance A from
26
402 FURTHER EVOLUTION
the simpler substances B, C or D which were present in
sufficient amounts in the surrounding medium. This would
then be repeated for substance B when it disappeared from
the external medium, and so forth.
Thus, the ability to synthesise any particular complicated
component of protoplasm must depend on each separate link
in the process having arisen successively in the course of the
prolonged evolution of organisms. According to Horowitz,
the first living things must have been completely hetero-
trophic in the sense that they needed ready-made, compli-
cated, organic compounds for the building up of their bodies.
Even for such building up, however, energy was needed
and the source of energy most readily available when the
organisation of the living bodies was still primitive was, once
again, organic substances. They contain large, hidden stores
of potential energy which can be mobilised comparatively
easily in the course of their degradation and used for bio-
synthesis either by means of linked reactions or by the forma-
tion of high-energy compounds. The exploitation of any of
the other kinds of sources of energy in the external medium
would have required the presence in the organism of acces-
sory systems which could only have arisen in the course of
very prolonged evolution.
It is quite clear that the mobilisation of energy by the first
organisms could only have been brought about by the
anaerobic degradation of organic substances, as there was no
molecular oxygen in the atmosphere of the Earth under the
reducing conditions which prevailed at the time when these
organisms existed. Only when free gaseous oxygen appeared
in the atmosphere did there arise the theoretical possibility
of oxidising organic substances completely, in order to use
the energy locked up in them. In order to realise this possi-
bility, however, the organisms must, in addition to their
primary, anaerobic, energy metabolism, have created in
the course of their evolution, under the new conditions of
the external medium, new oxidative enzymes and new
systems of reactions which certainly could not have arisen
at earlier periods in the history of life when the atmosphere
was of a reducing nature.
The gradual complication and integration of both the
FIRST HETEROTROPHS AND ANAEROBES 403
synthetic and energy-yielding reactions of metabolism could
not occur as a single process following a direct course.
It followed different and very divergent paths in different
representatives of the living world. As this went on, some
organisms were quicker to acquire the power to synthesise
complicated organic compounds, while others set up mechan-
isms which enabled them to use a greater variety of sources
of energy. Owing to this, the heterotrophic nature of con-
temporary organisms, their dependence on organic nutri-
ment, is very diverse. For example, some representatives of
the genus Hydrogenomonas do not require organic nutrients
for their energy metabolism and can use co, as the sole source
of carbon for the construction of their substance, though they
cannot synthesise the prosthetic groups of some of the
enzymes which they need. They have to obtain these ready-
made from the environment, as vitamins, otherwise they
cannot exist.^
Moulds, on the other hand, have a very highly developed
ability to synthesise various very complicated organic com-
pounds, vitamins, antibiotics, etc., but they are typical hetero-
trophs in the sense that they can only grow on organic sub-
strates (e.g. on sugar solutions) which act as non-specific
sources of energy and carbon for the construction of the
components of their protoplasm.*^
In view of this, the concept of heterotrophy itself is far
less simple than it might seem at first glance. The classifica-
tion of various organisms according to their nutrient require-
ments which are current in scientific literature at present
(e.g. those of R. HalF and A. Lwoff^) are very complicated
and often rather confusing as well. Attempts to form a
picture of the progress of the evolution of organisms in this
respect are even more contradictory'' ^° because, in some
cases, an obligatory requirement for some particular organic
substance may also arise secondarily owing to the dropping
out of some chemical, metabolic mechanisms which had been
elaborated at a preceding evolutionary stage.
It is, nevertheless, a self-evident and generally accepted
fact that the overwhelming majority of biological forms now
living on our planet can only exist in the presence of ready-
made organic substances.
404 FURTHER EVOLUTION
This includes all animals, both higher and lower, among
them most of the protozoa, the vast majority of bacteria and
all fungi. This fact by itself is very significant. It is, in fact,
hardly possible to imagine the evolution of all these multi-
farious living things, entirely in accordance with the simpli-
fied scheme suggested by Bateson, as the complete loss of that
ability to nourish themselves autotrophically which they once
possessed.* This is also contradicted by intensive biochemical
studies of the whole metabolic system of these organisms. In
the heterotrophs we do not find the specific enzymic com-
plexes and concatenations of reactions which are character-
istic of autotrophs. On the other hand, the metabolism of
autotrophs is based on the same internal chemical mechan-
isms as that of all other organisms which can only exist by
consuming organic substances. This is what allows autotrophs
under some conditions to revert so easily to heterotrophy.
This can be confirmed, not only by rather intricate bio-
chemical analyses of the metabolism of different organisms,
but even by comparatively simple physiological observations
on their nutrition.
The colossal amount of factual material at the disposal of
contemporary students of vitamins and essential amino acids
shows clearly how widely the requirements for specific, ready-
made, organic compounds are distributed among all the
inhabitants of the world. Of course, these requirements may
arise secondarily in a number of individual cases, as a result
of a certain regression, the dropping out of particular syn-
thetic mechanisms which had previously been built up in the
organism. For example, it is possible by certain procedures
to cause some particular bacteria, which were previously
able to synthesise all the essential amino acids which they
required, to lose this ability.^^ The relative ease with which
' mutants ' of this sort can be obtained indicates that the
synthetic mechanism in question is not fundamental to the
metabolism which enables the organisms to remain alive.
The mechanism can be destroyed or removed but the organ-
ism continues to exist so long as the surrounding medium
contains the amino acids or vitamins which it needs.
* An extended critique of hypotheses of this sort is given in V. Polyanskii's
interesting article. ^ — Author.
FIRST HETEROTROPHS AND ANAEROBES 4O5
This sort of requirement for ready-made, specific, organic
substances may be met with under natural conditions in
organisms at the most varied levels of the evolutionary scale,
not only among obligate heterotrophs, but even in organisms
which in all other respects can dispense with organic nut-
rients.
As we have already seen in the case of Hydrogenomonas,
even chemoautotrophs sometimes require specific organic
nutrients such as vitamins, although in general they may
serve as examples of organisms in which there have been set
up, during the course of evolution, extremely thoroughgoing
mechanisms for the carrying out of diverse syntheses.
This is true to an even greater extent among the photo-
autotrophs, many of which, either during the whole of their
life cycle, or at particular stages of it, require exogenous
organic substances such as vitamins, growth factors, essential
amino acids, etc. This concerns the lower chlorophyll-contain-
ing organisms in particular. Thus, for example, some species
of green flagellates like Euglena, even when grooving in light,
cannot do without amino acids or peptones for building up
their bodies, while other species, although they can use min-
eral nitrogen, can equally well use amino acids as nutrients. ^^
The requirement for vitamins, in particular for vitamin
Bi and various gi'owth factors, is very widespread among
most of the algae, among the blue-green algae and diatoms
as well as among the green forms. ^*
E. G. Pringsheim^^ has already pointed out that exogenous
organic substances must be addecl to pure cultures of algae,
and now various organic extracts are always added when
growing such cultures (except, of course, when special investi-
gations are being carried out).
The situation in regard to vitamin Bjo in various algae is
extremely interesting. Although algae contain a large amount
of this vitamin they cannot synthesise it but obtain it from
symbiotic bacteria.^®
Intensive investigations have shown that, in other cases
too, the extremely widespread occurrence of the parasitic
mode of life among many algae is associated with their
requirement for specific organic substances. This applies, in
particular, to the symbiosis established in lichens^'^ and the
406 FURTHER EVOLUTION
constant presence of algae within the bodies of some infusoria
and other kinds of animals. The scientific literature also
contains references to large numbers of cases of parasitism,
not only among green algae, but also among blue-green,
diatomaceous and brown and purple forms. ^*
In this, as in other forms of parasitism, regression undoubt-
edly takes place, the loss of the internal chemical abilities
which the original organism possessed and which enabled it
to build up the necessary organic substances autotrophically.
However, this return to the past could not occur so readily
unless there were already present some phylogenetically
earlier mechanism for heterotrophic nutrition.
The higher green plants which have a very highly devel-
oped apparatus for the synthesis of different substances have,
to a large extent, freed themselves from dependence on pre-
formed vitamins, if we consider the organism as a whole.
Nevertheless, separate parts of such plants grown in isolation
in tissue cultures are absolutely dependent on an exogenous
supply of vitamins and other organic substances."
Not only do many green photoautotrophs need specific
organic substances but, in general, they can all very easily
be induced to nourish themselves on ready-made exogenous
organic compounds, notwithstanding the fact that during the
process of evolution, they long ago acquired the ability to
synthesise these substances for themselves from mineral salts
at the expense of energy derived from sunlight. Such an easy
transition to ordinary heterotrophism demonstrates once
more that the metabolism of photoautotrophs is based on
chemical mechanisms which can derive energy from ready-
made organic substances.
It is understandable that the less highly organised photo-
autotrophs are specially liable to manifest their tendency to
heterotrophism and revert to it with particular readiness
under both laboratory and natural conditions.
As an example of complete transition from autotrophic to
heterotrophic nutrition we may mention the experiments of
C. Ternetz-" and a number of later authors on Euglena.
Starting from the green forms of this organism it is possible
to obtain completely colourless forms which can only nourish
themselves heterotrophically. This is done by cultivating
FIRST HETEROTROPHS AND ANAEROBES 407
the Euglena on organic substrates in the dark, or even in
the hght when the medium is very rich in organic substances.
The colourless cultures obtained in this way can live and
glow for many years because they can nourish themselves by
purely heterotrophic means.
As early as the beginning of the twentieth century it was
shown that if algae were supplied artificially with organic
substances it had a very favourable effect on their growth
and development.^^ The direct experiments of A. Artari-^
on the utilisation of organic substances by pure cultures of
algae showed that glucose, fructose, maltose, sucrose, pep-
tones, asparagine, lysine, glycerol, mannitol, inulin and
many salts of organic acids formed excellent nutrients for
many unicellular forms of green algae. When supplied with
these substances the algae develop equally well in the light
and in the dark.
Later experiments" established beyond doubt that when
organic substances are introduced into cultures of green algae
they are assimilated directly. This may occur alongside the
process of assimilation of CO2, but in some cases this process
may be put out of action and the algae turn over to an
entirely saprophytic way of life. Under these conditions
blue-green algae such as Nostoc/^ diatoms and such green
algae as Spirogyra flourish luxuriantly.
Working with soil algae (Scenedesmiis costulatus) B. M. B.
Roach^^ established that they could grow in the dark on
media to which glucose had been added as a carbon-contain-
ing nutrient. C. B. Skinner and C. G. Gardner^® showed
that, in pure cultures of green algae, casein, albumin and
glucose could serve as nutrients for the organisms. Nowadays
media composed of potatoes, meat peptones or wort are
successfully used for the culture of various algae. ^'^
It would appear that many blue-green and other algae can
use the organic materials found in mud under natural con-
ditions too. This is indicated by the very fact that they
develop specially luxuriantly in stagnant waters and in other
similar places which are rich in organic substances.
The view that heterotrophy is the primary mode of nutri-
tion is also supported by the results of investigations on
higher green plants (i.e. organisms which have long been
408 FURTHER EVOLUTION
adapted to the autotrophic way of life). Only those cells in
them which contain chlorophyll possess the chemical mechan-
ism for photosynthesis. It is in them alone that there occurs
that primary synthesis of organic substances which are used
as nutrients by all the rest of the colourless tissues of the
plant. These are nourished in a purely heterotrophic way
just as fungi are nourished by the addition of sugar to the
culture medium. The leaves, too, are nourished in this same
way in the absence of light.
Thus, the metabolism of the plant as a whole is based
on a heterotrophic mechanism using organic substances as
nutrients although, in its green tissues, this mechanism is
combined with an additional specific apparatus whose func-
tion is to supply the whole organism with ready-made organic
substances. If the plant is supplied in some way with such
substances from without, it can exist even without its photo-
synthetic apparatus. This takes place under normal natural
conditions, in particular during the germination of seeds. It
can be demonstrated experimentally by, for example, raising
a whole adult plant of the sugar beet in the dark from a
one-year-old root. Finally, it may also be observed in cases
where higher plants have lost their ability to synthesise owing
to having become parasitic, e.g. in broomrapes.^*
In all these cases the plant lives and nourishes itself on
exogenous organic substances while its photosynthetic auto-
trophic apparatus is completely inactive. But if even one link
of the enzymic chain of heterotrophic metabolism is dis-
rupted, all the vital activities of the plant cease and it is
destroyed. This may be observed, in particular, during the
specific poisoning of phosphoglyceraldehyde dehydrogenase
\s ith monoiodoacetic acid or of enolase with sodium fluoride. ^^
Hence it is quite clear that the vital processes of photo-
autotrophs, including the higher plants, are based on the
primary and ancient heterotrophic form of metabolism while
the ability to synthesise organic substances by using the
energy of light only arose in them as an accessory apparatus
on this basis.
The situation is less clear in regard to the chemoauto-
trophs, mainly because their metabolism is, as yet, very little
studied in comparison with that of other organisms. Even
FIRST HETEROTROPHS AND ANAEROBES 409
in the time of S. Vinogradskii^" it was suggested in regard
to these organisms (as well as to the more pronounced auto-
trophs which can develop in purely mineral media) that
organic substances not only were not assimilated by them but
actually hindered their gi'owth, i.e. were toxic to them.
This idea had its theoretical basis in the preconceived
conviction, which was referred to in Chapter IV, that the
first organisms must have been able to make organic materials
for themselves because none were present on the Earth before
the origin of life.
For this reason the chemoautotrophs were also regarded
as extremely primitive organisms, the organisation of which
lacked the chemical mechanisms which enabled all other
living things to use organic substances as sources of energy
and as immediate structural materials for the synthesis of the
components of their protoplasm.
This idea of the primitiveness of the metabolism of chemo-
autotrophs was due to the fact that our knowledge of it was,
and to some extent still is, very limited. But the further
the study of this field progresses the clearer it becomes that
the organisation of the metabolism of chemoautotrophs is
very complicated in comparison with that of many other
living things. ^^ Their ability to use energy derived from the
oxidation of inorganic substances for the synthesis of the
components of their protoplasm is not due to the simplicity
of their organisation. On the contrary, they manifest a high
degree of complexity and integration which could not, by
any means, be primary but must have arisen as a result of
prolongeci evolution. This is indicated by the fact that the
overwhelming majority of chemoautotrophs are markedly or,
so to speak, * essentially ' aerobic. The characteristic reactions
on which their autotrophy is based take the form of the
oxidation of reduced inorganic compounds by molecular
oxygen. The catalytic mechanisms underlying these reactions
could obviously not have arisen during the period when
reducing conditions prevailed on the Earth. They could only
have been elaborated secondarily, when the atmosphere of
our planet had been considerably enriched with free oxygen.
It is very characteristic of chemoautotrophs that a more
searching investigation of their complicated metabolism
410 FURTHER EVOLUTION
reveals the presence, alongside these oxidative mechanisms,
of the same enzymic complexes which form the basis of the
heterotrophic and anaerobic metabolism of all other living
things. This is what allows many chemoautotrophs to go over
readily to a heterotrophic way of life under certain circum-
stances.
Actually, facts have been assembled in the scientific litera-
ture for a comparatively long time indicating that many
organisms which can exist as pure chemoautotrophs can, at
the same time, assimilate organic substances very well. This
was established for hydrogen bacteria as early as 1910 by
A. Lebedev^^ and was later confirmed by W. Ruhland.''^ K.
Trautwein^* and R. L. Starkey^^ working with Thiobacillus
trautweinii, and P. A. Roelofsen^^ and M. S. Cataldi^^
working with other sulphur bacteria, showed that these can
grow heterotrophically in the absence of oxidisable inorganic
substrates and in the presence of the organic substances
which they require. The same was established for many iron
bacteria by the experiments of H. Molisch,^^ R. Lieske,^^
M. S. Cataldi,*° V. O. Kalinenko" and others.
In presenting an account of the extensive experimental
evidence which has now been collected, C. B. van Niel*^
reaches the conclusion that organic substances have a less
deleterious effect on most chemosynthetic bacteria than is
commonly supposed. Only Nitrosomonas, Nitrobacter, four
species of Thiobacillus (in particular T. thiooxidans and
T. thioparus) and forms related to these species can be con-
sidered as ' strict ' autotrophs (and this only in a somewhat
provisional sense). All the other chemoautotrophs, according
to van Niel, are not obligate autotrophs but can make
extensive use of the energy of organic compounds.
However, it has recently been established that even those
few species of chemoautotrophs {Thiobacillus thiooxidans
and the nitrifiers) which, for reasons which are still unknown,
cannot assimilate the organic substances contained in the
surrounding medium, can nevertheless carry out internal
respiration which proceeds by the oxidation of polysacchar-
ides which they have accumulated within their cells. These
transformations are brought about by the same glycolytic
mechanisms which operate in typical heterotrophs.*^- ^* This
FIRST HETEROTROPHS AND ANAEROBES 41I
was shown for T. thiooxidans in particular by the experi-
ments of K. G. Vogler, W. W. Umbreit and other authors
^vho have collaborated with them/^ According to Umbreit,
when sulphur is oxidised by this organism there occurs a
phosphorylation analogous to that which takes place during
the oxidation of organic compounds by heterotrophs. During
this process the energy derived from the oxidation is fixed in
high-energy organic compounds of phosphorus, such as ATP,
so that it can be used later ^vhen cOo is assimilated under
anaerobic conditions. Doubt has been cast on these conclu-
sions by a number of authors (K. Baalsrud and K. S.
Baalsrud,^® R. W. Newburgh*'^ and others). However,
Umbreit completely confirmed his ideas by further experi-
ments using more refined isotopic methods.** Studies of the
phosphorus compounds which accumulate in the cells of
T. thiooxidans during the oxidation of sulphur, carried out
by G. A. LePage and W. W. Umbreit"^ and later by H. A.
Barker and A. Kornberg,^" revealed the presence of labile
polyphosphates, ATP and such typical metabolites of glyco-
lysis as phosphohexoses and phosphotrioses. During a period
of intensive oxidation of sulphur and assimilation of cOo T.
thiooxidans synthesises a store of polysaccharides ; the endo-
genous destruction of this is carried out by means of a glyco-
lytic mechanism which is present in these bacteria.
Thus, even in regard to such typical ' strict chemoauto-
trophs ' as T. thiooxidans, the position is analogous to that
which we have discussed above in regard to green plants.
The metabolism of both groups of organisms is based on
the heterotrophic utilisation of organic materials while the
autotrophic mechanisms which are superimposed on this
basis enable the organism which possesses them to exist under
a greater diversity of external conditions. ^^
Umbreit's results have also been confirmed by work with
other chemoautotrophs. For example, it has been shown that
in hydrogen bacteria there is an accumulation of organic
phosphorus (mainly in the form of ATP) when hydrogen is
oxidised in the absence of CO2, while the amount of such
compounds present decreases rapidly during the process of
assimilation of CO2. Analogous results have been obtained
412 FURTHER EVOLUTION
by Yu. I. Sorokin" for one of the chemoautotrophs, Vibrio
desulfuricans.
According to H. Lees," who has recently done a lot of
work on the metabolism of Nitrosomonas, this organism, like
other chemoautotrophs, uses the energy derived from the
oxidation of inorganic substrates for the assimilation of CO2.
In satisfying the internal requirements of the cell, it may
use another source of energy, heterotrophic respiration based
on the carbohydrates which have been formed. However,
this suggestion still requires further experimental amplifica-
tion/^
It remains obscure why typical ' strict ' chemoautotrophs
which have the appropriate catalytic mechanisms cannot
work up the exogenous organic substances present in the
surrounding medium. Some authors ascribe this to peculiar-
ities of the permeability of the cell membranes of these
organisms^' but it must be pointed out that very little factual
material bearing on this has been collected. In particular,
experiments on the nutrition of chemoautotrophs on organic
substances have only been carried out for a very limited
number of such substances, chiefly glucose, other sugars,
amino acids and their polymers. However, this does not
show that the organisms tested are absolutely unable to
nourish themselves on organic matter.
In this connection we may note the following interesting
fact. We now know that there are organisms which are quite
unable to assimilate sugar and other analogous compounds,
but which can make good use of such sources of carbon for
their nutrition as toluene, phenol, salicylic acid and other
typical antiseptics which are very poisonous to all other living
things. The literature contains accounts of curious situations
in which attempts to sterilise soil with toluene, which is
commonly used for this purpose, did not bring about destruc-
tion of the microflora, but, instead, the greater proliferation
of some members of it.^® These so-called ' cyclists ' have been
studied in detail by V. O. Tauson in particular." He isolated
them from the soil of petroleum-bearing regions which con-
tained a considerable number of bacteria and other organisms
which could break down both petroleum and various fractions
of it, kerosene, fuel oil, paraffin, lubricating oil, etc. The
FIRST HETEROTROPHS AND ANAEROBES 413
organisms use the hydrocarbons obtained from these mixtures
as their sole sources of carbon and of energy. From a study
of these organisms Tauson^* came to the conclusion that their
inability to use glucose, fructose, mannitol, glycerol, tartaric
acid and other similar compounds, which serve as satisfactory
sources of carbon for most living things, was due to their
inability to transform the primary alcohol groups into methyl
groups. Thus the ' cyclists ' (like other hydrocarbon-using
organisms) cannot form acetaldehyde from carbohydrates and
this prevents them from being able to synthesise fatty acids
and the carbon skeletons of amino acids. They use another
means to this end, namely the breakdown of the benzene
nucleus of cyclic compounds, and thus obtain only partly
hydroxylated carbon chains which then serve as material for
the building of the proteins and lipids of protoplasm. This
suggestion of Tauson's certainly still requires further study
and biochemical confirmation.
However, even if we accept Tauson's views, it is still hard
to decide whether this metabolic peculiarity is, as Tauson
thought, an expression of the primitiveness of the ' cyclists ',
or whether it arose secondarily as an adaptation to circum-
stances in which hydrocarbons were the most readily avail-
able nutrients. The latter is the more probable. In the first
place this is suggested by the extensive material put forward
by C. E. Zobell,^^ which shows that among hydrocarbon-
using organisms there are living things belonging to very
diverse systematic groups including bacteria, yeasts and
moulds. Another fact which suggests that the ability of these
organisms to use hydrocarbons as nutrients is of secondary
origin is their pronounced aerobic habit, though some of
them can also exist without free oxygen. As an example we
may here cite Tauson's work on Microspira spp.®° Under
strictly anaerobic conditions (in the deep layers of the crust
of the Earth) these organisms can oxidise paraffins as well as
naphthalene, phenanthrene and other polycyclic compounds
while simultaneously reducing sulphates to hydrogen sul-
phide.
Although the metabolism of hydrocarbon-using organisms
has received very little study as yet, one can nevertheless find
in them the general methods of transformation of organic
414 FURTHER EVOLUTION
compounds, common to all living things. In particular, de-
hydrogenase systems®^ and enzymes catalysing the rupture of
carbon-carbon bonds (aldolases) have been shown to be
present. Another piece of evidence tending in the same
direction is the fact that we find, as intermediate products in
these organisms, the organic acids, aldehydes, alcohols, etc.,
which are common to all other organisms.®^
The relationship between the metabolism of the hydro-
carbon-using organisms and that of typical heterotrophs is
also confirmed by the ability of some living things, which can
oxidise hydrocarbons, also to thrive in glucose solutions.
Pseudomonas fluorescens may serve as an example ; it is well
able to oxidise hydrocarbons®'' but, at the same time, it is a
classical subject for the study of the glycolytic and oxidative
degradation of sugars.
Thus, whichever group of microbes, plants or animals we
consider in detail, we can establish that their metabolism is
based on an ability to use organic substances as sources of
energy and of structural materials for the formation of the
components of protoplasm. This ability is common to all
living things. This process is characteristic, not only of
clearly-defined heterotrophs, but also of autotrophs, in which
it may always be found alongside the specific mechanisms
which enable them to build up organic from inorganic sub-
stances. In contrast to this, heterotrophs show no traces of
autotrophic mechanisms though some odd vestiges of these
must surely have been retained if the heterotrophs had arisen
by regression from autotrophic ancestral forms.
In 1914, A. Lebedev's experiments with moulds®* indicated
that these typical heterotrophs could fix carbon dioxide, and
this was later established for other analogous microbes, in
particular for heterotrophic bacteria.®^ Some authors natur-
ally took this fixation to be a vestige of autotrophy in these
organisms. Such a view was only to be expected at that time,
when the assimilation of CO2 was held to be the exclusive
prerogative of autotrophs and the ability to assimilate it Avas
recognised as the criterion for distinguishing between them
and heterotrophs.
However, as studies of this subject developed further, so
the circle of living things which had been shown to be able
FIRST HETEROTROPHS AND ANAEROBES 415
to fix carbon dioxide became wider and wider/^ although
the biological significance of the phenomenon remained
obscure. The fact is that fixation of any kind needs energy.
Taking it over all, photosynthetic organisms use the energy
of light for this purpose while chemosynthetic organisms use
energy derived from the oxidation of hydrogen sulphide,
ammonia, ferrous oxide, etc. By these means the amount of
organic substances is increased at the expense of the carbon
of CO2 and the stored potential energy of the living cells.
When heterotrophs fix co,, on the other hand, they use the
energy which they obtain from the degradation or oxidation
of ready-made organic substances and thus the .process is not
accompanied by any increase in either their stored organic
carbon or their stored energy. Their over-all balance is
negative in both respects, as may easily be shown by direct
determinations.
In view of this, the widespread occurrence of heterotrophic
fixation of carbon seemed incomprehensible. Furthermore,
later studies, especially those involving the use of CO2 contain-
ing labelled carbon atoms, showed beyond doubt that the
ability to fix carbon heterotrophically was in fact possessed
by all known living cells," not only by microbes'^* but also
by animals*^^ and even by the colourless cells of higher plants
which can only live heterotrophically, e.g. the cells of roots. ^°
As we now know, the fundamental protoplasmic mechan-
ism taking part in the initial stage of the fixation of CO2 in
both autotrophs and heterotrophs is coenzyme A. This was
discovered by F. Lipmann^^ during a study of processes of
acetylation in living tissues and also studied simultaneously
in several other laboratories (D. Nachmansohn and M. Ber-
man,'^^ W. Feldberg and T. Mann" and others).
The significance of coenzvme A is, essentially, as follows.
Acetic acid plays a very important part in the metabolism of
every living organism. It seems to be a connecting link
between the metabolism of carbohydrates, fats and proteins.
By itself, however, it is chemically inert and before it can
enter into reactions of acetylation or condensation it must be
activated in some way. This is done by the formation of an
acetyl derivative of coenzyme A, which was first isolated in
the pure state from yeast by F. Lynen, E. Reichert and L.
4l6 FURTHER EVOLUTION
Rueff.^* This ' active acetate ' is a thioester of acetic acid
with coenzyme A :
,0\ N,
0 0
\
-P 0 P 0 — CHj — CH CH N C CH
0 ^« \h_/oh <
I
0PQ3H, I
OCH2. C (CHj)^. CHOH. CO. NHCHo. CHo. CO. NHCH.,. CH^S. CO. CH3
The thioester bond of coenzyme A is associated with a large
supply of energy and when it is broken by hydrolysis 8,200
cal/mole are liberated. ^^ Thus acetyl coenzyme A may be
described as a ' macroergic ' compound. It must arise during
metabolism at the expense of energy derived from the phos-
phate bonds of ATP or from a simultaneous oxidation
according to the equation^®
CH3CO.C00H + coenzyme A + ^Oa^
acetyl coenzyme A + CO2 + H2O
However, this oxidation does not require the presence of free
oxygen, it can also occur anaerobically with the transfer of
hydrogen to other organic substances through the mediation
of diphosphopyridine nucleotide. When it has been activated
in this way by coenzyme A, the acetyl residue can enter into
the most diverse condensation reactions leading to the forma-
tion of new carbon-carbon bonds and the lengthening of the
carbon chain.
It later appeared that coenzyme A can activate, not merely
acetic acid, but also other organic acids of both the aliphatic
and aromatic series which also form thioesters with coenzyme
A, e.g. succinyl coenzyme A" and ?50valeryl coenzyme A.^®
The tremendous biological importance of coenzyme A rests
on the fact that only through its mediation can small organic
molecules combine together by carbon-carbon bonds to form
complicated organic substances. That is to say, this is the
only way in which one of the most important processes in
the synthesis of the carbon skeletons of the components of
protoplasm can take place. It is quite clear that a process
FIRST HETEROTROPHS AND ANAEROBES 417
of this sort must have occurred in e\en the very earhest
hving things, it must have arisen concurrently with Hfe. It
is, therefore, to be found in all organisms without exception,
in particular in such typical heterotrophs as the bacteria
responsible for butyric acid fermentation, in which the actual
formation of butyric acid results from the reductive con-
densation of two acetyl residues.
What has been said accounts for the extremely widespread
occurrence, not to say uni\'ersality, of coenzyme A, which
has been found in all organisms in which it has been looked
for.
'Active acetyl ', however, is not used only for the condensa-
tion of two molecules of acetic or analogous acids, it can also
be used for bringing about the combination of these acids
with cOo. The very presence of acetyl derivatives of coenzyme
A therefore necessarily implies the possibility of the fixation
of CO,.
Studies in this field do indeed show that when CO2 is fixed
its labelled carbon atoms always appear in carboxyl gioups
combined with pre-formed organic molecules containing not
less than two carbon atoms. In particular we may indicate
the following types of reaction whereby co, is fixed by some
heterotrophs."
(c„ + Ci) Clost. butylicum
Acetate -f cOo -j- h. >pyruvate + h.o
(C3 4- Ci) M. lysodeikticus
Pyruvate -f cOo >oxaloacetate
(C4 + Ci) Esch. coli
Succinate -\- CO2 + h, >a-oxoglutarate 4- HoO
As a rule, heterotrophs cannot synthesise substances in
which two neighbouring carbon atoms are derived from cOo,
the ability to do this being peculiar to autotrophs, which
build the whole of the carbon skeletons of the components
of their protoplasm out of carbon dioxide which they have
fixed.
However, K. T. Wieringa,*" and later H. A. Barker and
his colleagues," have succeeded in isolating bacteria which
require organic nutrients for their growth and development
27
4l8 FURTHER EVOLUTION
but at the same time can synthesise acetic acid in such a way
that both carbon atoms are derived from cOj^ as may be
shown by studies using labelled carbon atoms. This relates
these bacteria to the typical autotrophs which have an analo-
gous method of fixing cOj.
It follows from all that has been said that the fixation of
CO, is a universal process and thus also very ancient, forming
the very foundation of the organisation of the metabolism of
all living things.
In heterotrophs it does not itself play a significant part,
but only accompanies more important synthetic reactions.
However, in the transition to autotrophy, the ability of the
primaeval organisms to carry out this reaction was of the
utmost importance. It was only on this basis that, in the
course of their further evolution, organisms were able to
free themselves from dependence on organic nutrients,
derived from the external medium.
Thus the heterotrophic fixation of co, would not appear
to be a vestigial form of autotrophy. On the contrary, it
constitutes an extremely ancient and universal mechanism,
present in even the most primitive organisms, a mechanism
which formed the basis for the later development of auto-
trophy in the course of progressive evolution.
Summing up all that we have discussed, it must be
admitted that the metabolism of all the multifarious organ-
isms now living on our planet is based on processes involving
the use of ready-made organic substances as starting materials
for building the components of protoplasm and as sources
of the energy required for life. This process is extremely
ancient, it is primary, whereas the chemical mechanisms used
by some living things to synthesise organic substances from
inorganic materials and supplies of energy arose alongside
of it during the course of the further evolution of organisms.
In full agreement with this, we find that the overwhelming
majority of organic forms can still only nourish themselves
heterotrophically, while those special groups of living organ-
isms which have acquired autotrophic mechanisms during
their evolution can comparatively easily revert to their earlier
nutritional habit.
ENERGY METABOLISM 419
Different forms of energy metabolism.
It would seem, at first glance, that the position is reversed
with the second cardinal thesis which we enunciated earlier,
that is, the primary nature of the anaerobic degradation of
organic substances. Only a veiy limited number of species
of bacteria and other lower organisms are obligate anaerobes,
living out the whole of their life cycles in the absence of
molecular oxygen. Other micro-organisms, such as yeasts,
are facultative anaerobes. But the overwhelming majority
of contemporary living things, especially all higher plants
and animals, cannot do without the free oxygen of the atmo-
sphere.
This state of affairs is highly significant because, under the
oxidising conditions of the present time, it is quite possible
to oxidise organic substances completely to carbon dioxide
and water, which mobilises a far greater amount of energy
than the simple anaerobic degradation of these substances.
It is therefore quite natural that contemporary living things
should, during the course of their prolonged evolution, have
become widely adapted to the most extensive use of the
conditions which prevailed on the surface of the Earth after
a considerable amount of free oxygen had been formed, i.e.
from about 700 million years ago.
It must, none the less, be admitted that anaerobiosis is the
primary way of life ; for a careful study of the energetics of
metabolism in the most diverse organisms, both lower and
higher, has shown convincingly that everywhere (even among
aerobes) this metabolism is based on strikingly similar and
completely universal anaerobic reactions of degiadation of
organic substances, while the very variegated mechanisms
which catalyse the combination of molecular oxygen with
the products of this degradation in different living things
are only superimposed on this basis.
This state of affairs was noticed as early as the end of last
century as a result of purely physiological investigations.
It was E. Pfliiger*^ who first discovered the so-called anaerobic
respiration of higher animals and put forward the view that
this process was not pathological and that it was not a minor
biological adaptation to enable organisms to survive a short
420 FURTHER EVOLUTION
period of lack of oxygen. In Pfliiger's opinion the ability to
degiade carbohydrates anaerobically formed the basis of the
whole of the normal respiratory process. Somewhat later a
similar state of affairs was shown by W. Pfeffer" to exist in
higher plants. He showed that, in the absence of atmospheric
oxygen, plants can carry out so-called intramolecular respira-
tion which is, chemically, completely analogous with alcoholic
fermentation. The much more recent studies of V. Palladin**
and, especially, S. Kostychev^^ showed that, in the great
majority of cases, the process of normal respiration also
begins with the anaerobic degradation of carbohydrates. If
air is available, however, the intermediate products of alco-
holic fermentation are oxidised to CO2 and water by means
of specific oxidative mechanisms. If free oxygen is artificially
excluded the process will usually lead to the formation of
small quantities of ethyl alcohol and carbon dioxide.
S. Kostychev*® gives the following diagram of the relation-
ship of the processes just referred to :
Sugar CgHioOe
intermediate products of fermentation
fermentation respiration
(2CO2 + 2C2H5OH) (6CO2 -t- 6hoO)
A very similar mechanism was described by Pfliiger in
animals and was later confirmed by the profound researches
of O. Meyerhof," G. Embden^* and J. K. Parnas*^ who showed
that the tissue respiration of animals was based on an anaero-
bic glycolytic process completely comparable with lactic
fermentation.
The primary nature of anaerobiosis is specially clearly
illuminated by a comparative study of the chemical nature
of the energy metabolism of the most diverse groups of con-
temporary living things. The essence of the biological concept
of energy metabolism is the mobilisation of the energy locked
up in organic compounds (of which carbohydrates are a
particular example) and its direction into the synthesis of the
components of protoplasm and into other processes necessary
for life. However, many obstacles lie in the way of this
ENERGY METABOLISM 421
transformation. In the first place the molecule of sugar,
or any other carbohydrate, does not break down spontane-
ously at ordinary, comparatively low temperatures and it is
therefore difficult to liberate the energy locked up in it. For
this to occur, a very high energy barrier must be surmounted.
In the second place, if the molecule of sugar were broken
down or oxidised completely and suddenly, there Avould be
something like an explosion, which Avould be associated with
such heating of the protoplasm at the point of the occurrence
that its existence would be rendered impossible. In the
course of their evolution, therefore, organisms have elabor-
ated chemical mechanisms of energy metabolism in which
sugar is broken do^vn gradually, by stages, rather than sud-
denly.
This gave the possibility, not only of surmounting the
barrier of the energy of activation of the separate reactions
at ordinary temperatures, but also of making rational use of
the energ}% which is then not liberated explosively, but step
by step in separate portions.
The energy of organic compounds liberated in this way
can usually be accumulated in high-energy compounds which
can then be used, by means of specific mechanisms, for the
synthesis of proteins, for muscular contraction, etc.
It must not, however, be supposed that energy exchange
takes place in the living cell as an isolated mechanism,
serving merely for the production of high-energy molecules.
In all processes of the biological destruction of organic sub-
stances (during fermentation, respiration, etc.) the straight-
forward task of storing energy is achieved, but the transfer
of electrons and hydrogen also takes place continually, as
well as the formation of those small fragments of the original
organic molecules which arise as intermediate breakdown
products and from which, in fact, the important components
of living material are directly synthesised. In this way organ-
isms are enabled to synthesise the tremendous variety of
extremely complicated substances which make up their
bodies, by the degiadation of a small number of non-specific
substrates.
By virtue of all this, the energy metabolism of any organ-
ism consists of a long chain (or even many chains) of well
422
FURTHER EVOLUTION
ETHYL
ALCOHOL
AND GASEOUS
CARBON DIOXIDE
LACTIC
ACID
WATER AND GASEOUS
CARBON DIOXIDE
2 ATP
jl ENOIPYRUVIC
2 COH ACID
I
COOH
2ADP ' ^2 CO®
pHOSPHO£NOLPyRUy/C COOH
ACID
CH,OH
2 CHO 0
2-PnOSPH06LYCERIC \
ACID COOH
CH,0®
5- PHOSPHOGLYCERIC
ACID
^ 2 CHOH
I ■
coori
2 ATP
'^'VERASt
2ADP
Fig. 36. Scheme of the reactioni
ENERGY METABOLISM
423
BLUCOSt
GLUCOSE- 6-PHOSPHATE
FRUCroSE-6-PHOSPHA TE
0OCH, /^ \^^ CHjOH
c
I
OH
REDUCTION OF
ACETALDEHYDE OR
PYRUVIC ACID
ATP
ADP
FRUCrOSE-l-6
DIPHOSPHATE
0OCH2// \,^^ CH,0@
► C
OH
DIHYDROXYACETONE
PHOSPHATE
CH.O^
I PHOSPHOTRIOSE
CO
f'°® rRlOSEPHOSPHATE_
C00@
/■3-D/PH0SPH06LYCERIC AC/O
involved in alcoholic fermentation.
c
I
H
GLYCERALDEHYDE
'3- PHOSPHATE
CHC; GLYCERALDEHYDE -I- 3- DIPHOSPHATE
424 FURTHER EVOLUTION
co-ordinated reactions, each of which is catalysed by its own
specific enzyme. Thus, this exchange of energy demands a
rather highly developed internal chemical mechanism, and,
the longer the chain of reactions, the more co-ordinated the
mechanism must be.
It would be theoretically possible to imagine an infinitely
large number of such chains of energy exchange, each
different in principle from the others both as regards the
individual reaction-links and as regards the general structure
of the whole chain. It is therefore very remarkable that
extensive biochemical researches have established the fact
that in all organisms which have yet been studied in this
respect, the energy metabolism is based on extremely similar,
almost identical, systems of reactions, catalysed by identical
enzymes. The system may vary from organism to organism,
but only in detail ; if one enzyme is absent another takes
its place, but, as a whole, it seems to be the same throughout
all the stages of evolutionary development of all the inhabi-
tants of the Earth, both anaerobes and aerobes. Among
aerobes new catalytic mechanisms have been added to the
original system, enabling them to use molecular oxygen.
To familiarise ourselves with the actual working of the
basic system we may consider the chemical mechanism of
alcoholic fermentation, which has now been thoroughly
studied. It takes place in a number of micro-organisms, of
which yeast would seem to be the most typical. The general
scheme of the reactions of fermentation as given by V. L.
Kretovich in his book,^° is shown in Fig. 36. The diagram
shows that glucose is transformed into ethyl alcohol and
carbon dioxide, without the participation of molecular
oxygen, by means of a series of strictly co-ordinated enzymic
reactions.
The process starts with the phosphorylation of glucose
with the help of the enzyme hexokinase. This involves the
transfer by hexokinase of a phosphate residue with a high-
energy bond (Af approx. 8,000 cal/mole) from ATP to a
glucose molecule. It leads to the formation of glucose-6-
phosphate and adenosine diphosphate (ADP). The glucose-6-
phosphate is then transformed into fructose-6-phosphate by
the enzyme oxoisomerase. The fructose-6-phosphate combines
ENERGY METABOLISM 425
with another high-energy phosphate residue from another
molecule of ATP, the reaction being catalysed by the enzyme
phosphohexokinase.
These preparatory reactions, involving the expenditure of
two high-energy bonds on each glucose molecule, lead to
the formation of fructose-i:6-diphosphate. This is followed
by a reaction catalysed by aldolase, the disruption of the
six-membered carbon chain into two trioses (glyceraldehyde-
3-phosphate and dihydroxyacetone phosphate) which can
undergo a mutual transformation, catalysed by the enzyme
phosphotriose isomerase.
In the process of fermentation glyceraldehyde-3-phosphate
undergoes a further transformation, being continually re-
placed at the expense of dihydroxyacetone phosphate. The
molecule of glyceraldehyde-3-phosphate undergoes dehydro-
genation while simultaneously combining with a phosphate
residue (derived from mineral phosphate) and a new high-
energy bond is thus formed in which is stored the energy
liberated by the removal of hydrogen from the glyceralde-
hyde-3-phosphate. The hydrogen thus liberated combines
with coenzyme I (DPN) Avhich constitutes the active group
of the enzyme triosephosphate dehydrogenase which catalyses
this reaction. This hydrogen can be used further for a
number of reducing transformations in the living cell ; in
particular, in alcoholic fermentation, it reduces acetaldehyde
to ethyl alcohol.
The i:3-diphosphoglyceric acid formed from the glycer-
aldehyde-3-phosphate gives its high-energy phosphate residue
to ADP. This reaction thus brings about the regeneration of
one of the two molecules of ATP which had earlier been
used for the phosphorylation of glucose. It is catalysed by
phosphopherase (phosphoglyceric phosphokinase).
The 3-phosphoglyceric acid formed from i:3-diphospho-
glyceric acid is converted, by the action of phosphoglycero-
mutase, into 2-phosphoglyceric acid which is transformed,
with the help of enolase, into phosphoenolpyruvic acid. In
this reaction 2-phosphoglyceric acid gives up water, which
leads to a rearrangement of the internal energy of the mole-
cule and the formation of a second high-energy bond at the
426 FURTHER EVOLUTION
expense of the alteration of the whole of that half of the
glucose molecule.
The high-energy phosphate residue thus formed is trans-
ferred to ADP and the second molecule of ATP is regener-
ated. The enolpyruvic acid then goes over to its more stable
form, pyruvic acid. The enzyme carboxylase splits off a
molecule of CO2 from the pyruvic acid and the acetaldehyde
so formed is reduced to ethyl alcohol by combining with the
hydrogen from coenzyme I.
How great is the amount of energy obtained by the
fermentation of a whole molecule of glucose?
As we have seen, the transformation of half a glucose
molecule (glyceraldehyde-3-phosphate) gives two high-energy
bonds which serve for the regeneration of the two molecules
of ATP which were used to phosphorylate the glucose. The
high-energy bonds derived from the second half of the glucose
molecule are a pure energy ' profit ' to the cell and can be
used for the synthesis of living matter or for other purposes.
Thus alcoholic fermentation is a process of anaerobic
breakdown of the glucose molecule, in which the energy
liberated by dehydrogenation accumulates in the form of
the high-energy bonds of phosphate residues and is carried
over in this form into the general metabolic system of the
cell through the agency of derivatives of adenylic acid, ADP
and ATP, with the help of the appropriate enzymes.
On considering the mechanism of alcoholic fermentation
one is struck by the large number of stages involved. The
reason for this is that it allows more effective use to be made
of the energy liberated by the breakdown of the sugar
molecule and also allows the formation of those fragments of
molecules from which the organism builds the carbon skele-
ton of its living material.
We find this ability to acquire energy by the anaerobic
degradation of organic substances by many stages in all the
different systematic groups of organisms, from the most
primitive bacteria to the highest mammals. Hence the
energy metabolism is based on anaerobic dissimilation of
carbohydrates similar to the process of alcoholic fermentation
which has just been expounded. Individual links in the
chain may vary and accessory superstructures may be elabor-
ENERGY METABOLISM 427
ated, but the basis always remains unchanged. In particular,
we find everywhere the same catalytic mechanisms and
methods of obtaining energy and accumulating it in high-
energy bonds. The differences, as we shall see belo^v, only
represent different ways of using the hydrogen liberated by
the process of dehydrogenation and different ways of further
transforming the breakdown products which are used for
btiilding the protoplasm of the living cells.
In the diagram of alcoholic fermentation given above, all
the hydrogen which is formed by the dehydrogenation of
glyceraldehyde-iig-diphosphate to the corresponding acid is
used, with the help of coenzyme I, for the reduction of
acetaldehyde to ethanol. In other cases the hydrogen may
be taken up by other intermediate products of metabolism
and used for reducing processes in the course of the bio-
synthesis of components of protoplasm, or oxidised to water
by the oxygen of the air in the course of respiration.
In all forms of anaerobic degradation of carbohydrates,
and in all organisms which have been studied in this respect,
pyruvic acid and its immediate derivatives occupy a key
position in the processes of biosynthesis of important com-
ponents of protoplasm, proteins, lipids, nucleic acids, etc.
The nature of the organisation of these synthetic processes
may, however, vary to some extent as between different
representatives of the living world. The processes of break-
down and synthesis may be co-ordinated to a greater or lesser
degree. During evolution this internal co-ordination there-
fore increases and at the same time there is an increase in
the coefficient of useful activity, the completeness wath which
the nutrient substances entering the living things from the
outside medium are used.
The anaerobic dissimilation of carbohydrates into alcohol
and CO2 is usually brought about by a number of different
sorts of bacteria in the way which has been described above
for yeasts. In some species of these micro-organisms, how-
ever, the individual links in the chain of fermentative
reactions may vary to a certain extent. We may cite, as an
example, Pseudomonas lindneri which, according to A. J.
Kltiyver and W. J. Hoppenbrouwers,®^ can form a larger
amotmt of alcohol. The general features of its metabolism
428 FURTHER EVOLUTION
agree with the scheme which has been given, but recently
M. Gibbs and R. D. DeMoss®^ have shown that the initial
stages of its metabolism deviate from the scheme in some
details. As soon as hexose-6-phosphate is formed it is de-
hydrogenated anaerobically to form 6-phosphogluconic acid.
This is then decarboxylated to give a pentose. The pentose
is broken down by the disruption of a carbon-carbon bond
to form alcohol and phosphoglyceraldehyde- 3 -phosphate
which is converted to alcohol in the same way as in ordinary
alcoholic fermentation by yeast.
In a group of typical obligately anaerobic bacteria, the
Clostridia, which can carry out butyric and acetone-butyl
alcohol fermentation, this takes place by essentially the same
method of glycolytic transformation of sugars as is found in
alcoholic fermentation. For example, the experiments of B.
Rosenfeld and E. Simon®^ showed that phosphoenol pyruvic
acid is formed during the process of acetone-butyl alcohol
fermentation. Pyruvic acid seems to be a necessary inter-
mediate product in other forms of butyric acid fermentation
but its further transformation in other bacteria of this group
gives rise to a whole range of different organic substances :
butyric acid, butyl alcohol, wopropyl alcohol, acetone, ethyl
alcohol, acetic acid, formic acid, hydrogen and carbon
dioxide.
For example, Clostridium acetobutylicum ferments glucose
with the formation of butyl alcohol, acetone, ethyl alcohol and
hydrogen. Another organism, CI. sac char obutyricum, forms
butyric and acetic acids, carbon dioxide and hydrogen.
Zymosarcina maxima forms butyric, acetic and lactic acids,
carbon dioxide and hydrogen.®*
The work of H. G. Wood and his colleagues,®^ and of
H. A. Barker,®® has established that the 4-carbon compounds
which are produced during various types of butyric acid
fermentation are formed by the condensation of active
residues of acetic acid, in the form of acetyl-coenzyme A,
with the formation of acetoacetic acid and its subsequent
reduction to butyric acid. Acetyl-coenzyme A is either
formed directly from acetic acid or from pyruvic acid by
anaerobic dehydrogenation and decarboxylation.
Acetone is formed by the decarboxylation of acetoacetic
ENERGY METABOLISM 409
acid. According to the results of H. J. Koepsell and his
colleagues," cell-free extracts of CI. hutylicum transform
pyruvic acid into acetyl phosphate, CO2 and hydrogen. Butyl
alcohol is produced by the reduction of butyryl-coenzyme A.
Thus we see that the anaerobic breakdown of sugar by
the various butyric acid bacteria is based on the same cata-
lytic mechanisms and the same sequence of reactions with
which we are familiar in alcoholic fermentation. The 4- and
3-carbon compounds characteristic of butyric acid fermenta-
tion are formed by the further anaerobic transformation of
pyruvic acid, that is to say, by the formation, transfer and
condensation of acetyl residues.
Another well-known example of anaerobic decomposition
of carbohydrates is provided by lactic acid fermentation
which is brought about by various species of facultative
anaerobes, e.g. Lactobacillus spp. and Streptococcus spp. The
main product of this fermentation is lactic acid, which is
formed by the dissimilation of sugar. In its initial stages this
process passes through the same intermediate reactions as
ordinary alcoholic fermentation, right up to the formation
of pyruvic acid. However, owing to the absence of carboxy-
lase, in lactic acid bacteria the pyruvic acid is not transformed
into acetaldehyde and cOo, but is reduced directly to lactic
acid.
In some lactic acid-producing bacteria such as Escherischia
coli or Strep, faecalis large amounts of acetic acid and
ethvl alcohol are formed as well as lactic acid. Here this
process can only take place anaerobically, by the anaerobic
dehydrogenation and decarboxylation of pyruvic acid. In the
course of this acetyl-coenzyme A is formed. At the same
time the hydrogen liberated by means of diphosphopyridine
nucleotide may be transferred to another molecule of pyruvic
acid, reducing it to lactic acid, or may react with one of the
two molecules of acetyl-coenzyme A which had been formed,
so that, in addition to acetic acid, ethyl alcohol is also formed.
Thus we see, here too, the same reactions and catalytic
mechanisms as are found in strictly anaerobic butyric acid
fermentation.'*' ®^ Unlike the bacteria which carry out this
fermentation, however, lactic acid bacteria are facultative
anaerobes and the organisation of their metabolism shows
430 FURTHER EVOLUTION
supplementary structural features which, to some extent,
enable us to understand the mechanism of the transition from
primary anaerobiosis to the aerobic way of life.
As we have shown, the reaction whereby acetyl-coenzyme
A is formed from pyruvic acid can take place, not only
anaerobically, but also with the participation of free oxygen.
The difference in this case is simply that the hydrogen set
free by dehydrogenation is not accepted by pyruvic acid or
acetaldehyde but is oxidised by oxygen.
This oxidative process does not occur spontaneously, it
requires special catalytic mechanisms which are completely
absent from obligate anaerobes because, in them, the reaction
can only follow the first path via the transformation of
pyruvic acid.
In facultative anaerobes, by contrast, there have been
found, alongside the ordinary glycolytic mechanisms, specific
catalysts promoting the oxidative decarboxylation of pyruvic
acid. Thus, according to the studies of I. C. Gunsalus and
his colleagues,^"" and L. J. Reed and colleagues,^"^ in Esch.
coli and L. delbrilckii and other bacteria this reaction is
catalysed by a complex compound of the amide of lipoic acid
and cocarboxylase which has been called lipothiamide pyro-
phosphate.
When facultative anaerobes are cultivated in the absence
of free oxygen these supplementary mechanisms are of no
significance. They can easily be excluded from metabolism ;
they remain ' unemployed ' but the bacterial cell continues
to exist satisfactorily on the basis of the old organisation. On
the other hand, in the presence of oxygen, the oxidative
.catalysts give a great advantage because they enable the
organisms in which they are present to make considerably
more rational use of the organic materials at their disposal.
It is obvious that, under the reducing conditions of the
primaeval atmosphere, only mechanisms subserving anaero-
bic metabolism could develop, while oxidative catalysts
were only formed as supplementary, and sometimes very
unimportant, accessories, after a considerable amount of free
oxygen had appeared on the surface of the Earth. This
is reflected in the organisation of present-day facultative
anaerobes.
ENERGY METABOLISM 43 1
The bacteria which carry out propionic fermentation may
serve as a furtlier example. Under anaerobic conditions their
metaboHsm is in complete accord with the scheme for alco-
holic fermentation ; sugar is broken dow^n to pyruvic acid
by means of the same enzymes and with the formation of
the same intermediate products as in yeast. The peculiarity
of these bacteria is that in them the pyruvic acid, which is
formed in the ordinary way, is not decarboxylated but, on
the contrary, combines with CO2 and is transformed into
oxaloacetic acid, which is first reduced to succinic acid and
then decarboxylated to propionic acid according to the
scheme :
2H2
CH3.CO.COOH + COo-^HOOC.CHo.CO.COOH ->
HOOC.CHo.CHo.COOH^ CH3.CH0.COOH + CO,.
All these reactions take place with the help of the mechan-
isms with which we have become familiar, in particular
coenzyme A and codehydrogenase. In the air, however,
these same bacteria can carry out the typical aerobic oxida-
tion of various organic acids, among them pyruvic acid.^"^
Accordingly they, unlike obligate anaerobes, are often found
to contain such oxidative mechanisms as cytochrome a^"^ and
the enzyme catalase.^"^
Like alcoholic fermentation, the anaerobic breakdown of
sugar is the basis not only of the energy metabolism of
facultative and obligate anaerobes ; the same glycolytic
mechanisms may also be found in typical aerobic bacteria
which, when living under natural conditions, absolutely
require molecular oxygen.
For example, in the strictly obligate aerobe Streptomyces
coelicolor, V. W. Cochrane"^ found the following enzymes :
phosphofructokinase. aldolase, triosephosphate isomerase,
triosephosphate dehydrogenase, phosphopherase, enolase and
ethanol dehydrogenase, i.e. the typical catalysts with which
we have become familiar in the scheme of alcoholic fermenta-
tion.
The acetic acid bacterium Acetohacter suhoxydans carries
out its energy metabolism by the aerobic oxidation of
hexoses. According to E. Simon'"'' it transforms hexose di-
432 FURTHER EVOLUTION
phosphate into trioses and then, via pyruvic acid and acet-
aldehyde, into acetic acid. If it is short of oxygen, however,
it begins to carry out ordinary alcoholic fermentation as it
has all the necessary enzymes.
When grown on a mineral medium with the addition of
glucose, Bacillus subtilis cannot carry out alcoholic fermenta-
tion and is obliged to exist aerobically. However, as N. D.
Gary and R. C. Bard^°^ showed, a culture of these bacteria,
grown on a medium containing glucose, tryptone and yeast
extract, grows under anaerobic conditions by carrying out
lactic acid fermentation. In such a culture one may find a
collection of the most important glycolytic enzymes.
Even in such well-defined aerobes as the obligate chemo-
autotrophs, in which the whole mechanism is directed
towards the oxidation of an inorganic substrate by oxygen,
there have been found, as we saw above, such typical glyco-
lytic mechanisms and intermediate products as diphospho-
pyridine nucleotide, ATP, phosphohexoses and phospho-
trioses.
Thus we see that among bacteria, which are the organisms
manifesting the greatest metabolic variety, we find every-
where that their metabolism is based on anaerobic degrada-
tion which follows the scheme for alcoholic fermentation.
This seems to be completely universal among these micro-
organisms. Only isolated groups of bacteria possess the
supplementary oxidative mechanisms, which must, obviously,
have arisen after the appearance of free oxygen in the atmo-
sphere of the Earth. The oxidative decarboxylation of pyruvic
acid by lactic acid bacteria may serve as an example of such
an original primitive mechanism. Later these mechanisms
became more complicated and were transformed into whole
cycles of orderly oxidative reactions which will be analysed
in more detail later, in connection with the problem of the
origin of respiration.
The glycolytic breakdown of carbohydrates also underlies
the energy metabolism of other primitive living things, in
particular protozoa. A. LwofF and his colleagues^"® found a
starch phosphorylase in Polytoma caeca. Adenosine mono-, di-
and triphosphates, glucose- 1 -phosphate, fructose-6-phosphate,
fructose- i:6-disphosphate and phosphogly eerie acid have all
ENERGY METABOLISM 433
been found in Euglena graciUs}^^ S. C. Harvey"" found a
series of glycolytic enzymes in cell-free extracts of Trypano-
soma equiperdum. The work of R. W. McKee"^ established
that Plasmodiii772 gallinaceum contains enzymic systems which
catalyse the phosphorylation of glucose by means of ATP,
the splitting of fructose diphosphate into triose phosphates
and the oxidation of glyceraldehyde-3-phosphate to pyruvic
acid. In these organisms, too, the oxidative degradation of
pyruvic acid was superimposed on the fundamental glycolytic
mechanism in the course of their evolution. Their metabol-
ism seems to be of an aerobic nature at present but, as we
have seen, it is based on glycolytic mechanisms.
Glycolytic mechanisms also form the basis of the metabol-
ism of another large group of heterotrophic organisms, the
fungi. It was, in fact, a representative of the lower unicellular
fungi (yeast) which served as the classical object for the study
of the chemical mechanism of alcoholic fermentation. In
other groups of fungi the energy metabolism is based on
glycolytic mechanisms, although many of these organisms
seem, at present, to be typical aerobes. The moulds, in par-
ticular, are of the greatest interest in this connection. They
are characterised by synthetic abilities peculiar among hetero-
trophs but they derive the energy needed for the synthesis
of various specific organic substances by heterotrophic means.
In them, as in bacteria and yeasts, the first stage in the
breakdown of organic substances is, as J. W. Foster rightly
remarked, a system of reactions similar to alcoholic fermenta-
tion, leading to the formation of pyruvic acid which later
undergoes oxidative transformation.
The researches of S. Kostychev and others and also the
more recent work of H. Tamiya and Y. Miwa"' have demon-
strated the occurrence of alcoholic fermentation in various
species of Aspergillus under aerobic conditions. Other Japan-
ese workers (T. Takahashi, T. Asai and K. Sakaguchi,"^' "*)
obtained active preparations of the zymase complex from
Rhizopiis and isolated carboxylase from them. J. C. Wirth
and F. F. Nord"^ sho\ved that a cell-free juice obtained from
the mycelium of a Fusarium contained active zymase.
According to the results of S. Kostychev and F. Black-
man,"® the systems whereby carbohydrates are broken down
28
434 FURTHER EVOLUTION
in green plants are no different in principle from those
found in bacteria and fungi. H. Gaffron and H. Michels^^^
both showed that the unicellular green alga Chlorella forms
lactic acid from glucose under anaerobic conditions. H.
Gaffron and J. Rubin^^^ showed that, under anaerobic condi-
tions, pure cultures of Scenedesmus give off CO2 and accumu-
late non-volatile organic acids, in particular lactic acid. In
connection with the extensive studies of photosynthesis
carried out by M. Calvin and his colleagues^ ^^ on the one
hand and by Gaffron and his group^^° on the other, it has
been shown that there are present in the cells of the green
algae Scenedesmus and Chlorella such important products
of the anaerobic breakdown of glucose as phosphoglyceric
acid, phosphopyruvic acid and hexose and triose phosphates.
In recent years an enormous amount of evidence has been
collected showing that the glycolytic system of Embden and
Meyerhof, which is found in higher plants, takes part in the
synthesis as well as in the degradation of carbohydrates. All
the enzymes concerned with alcoholic fermentation have
been found in higher plants and some have been isolated
in a purified state. ^^^ For example, coenzyme II (TPN)
(triphosphopyridine nucleotide) has been found in various
leaves and also in potato tubers. Hexokinase, an enzyme
mediating the use of high-energy bonds, has been found
in spinach leaves. Wheat grains and the seeds of other plants
have been shown to contain oxoisomerase, and so forth.
Intermediate products of glycolysis such as acetaldehyde,
ethyl alcohol and lactic acid were found long ago in the
tissues of higher plants when they are made to live under
anaerobic conditions. ^^^
The striking uniformity of the glycolytic mechanisms
which underlie energy metabolism is found by investigation
to prevail among animals from the simplest flagellates to the
higher mammals and man. On the basis of studies of various
zoological types, a number of scientists have expressed the
opinion that the process of respiration of oxygen, which plays
such an important part in the animal world, is of relatively
recent phylogenetic origin. It represents a specialised
mechanism which has arisen in the course of evolution on
the basis of the more ancient, universal mechanism for the
ENERGY METABOLISM 435
liberation of energy, namely the glycolytic breakdown of
carbohydrates with the formation of pyruvic and lactic acids.
This view w^as put forward by A. Piitter^-^ as early as 1905,
and, considerably later, by A. Szent-Gyorgyi^^* who held that
glycolysis represents a more ancient attempt by nature to
use energy. Indeed, in all the representatives of the animal
kingdom so far studied, the presence of the glycolytic cycle
of degradation of carbohydrates has been established. As we
sa'^v above, glycolysis occurs in protozoa and other primitive
animals. O. Harnisch^^^ found glycolysis in a number of
groups of insects {Periplaneta, Carausius, Bombus, Apis,
Eristalis). Glycolytic enzymes have been isolated from the
wing muscles of the grasshopper.^^'' Various representative
species of worms {Schistosoma mafisoni /^'' Neoaplectana
glaseri,^^^ and Hymenolepis diminuta^-^) possess glycolytic
systems, while molluscs can also decompose carbohydrates
anaerobicallv.^^"
At the conclusion of his extensive review of glycolysis P. K.
Stumpf"^ writes as follows :
Since a multitude of animals have been analyzed for the
presence of the cycle, it becomes impossible to itemize the activity
of each animal and organ. In general all tissues of higher animals
ranging from the internal organs to parts of the eye such as
the cornea, the crystalline lens, and the retina have been found
to contain the galaxy of glycolytic enzymes. Indeed, it would be
difficult to demonstrate its absence in cell tissue.
Nevertheless, in a brief listing of the tissues in which the
glycolytic system has been found unequivocally, hearts of the
eel, toad, turtle, and rat, cornea of the rabbit, retinas of the
guinea pig and lizard, chick embryos of different ages, leucocytes,
erythrocytes, frog embryos, semen from a variety of sources,
rabbit femoral and tibial bone marrow, human rib marrow,
mouse melanoma, Flexner-Jobling rat carcinoma (to mention a
few tumor tissues), gastric mucosa, brain and the various organ
tissues of the body have the glycolytic system as a functioning
unit.
A systematic survey of the evidence for the presence of
glycolysis in representatives of various groups of animals may
be found in a number of review works, in particular that of
J. P. Greenstein and A. Meister.^^^
436 FURTHER EVOLUTION
Consideration of the evolutionary aspect of all this material
leads one to concur with the opinion of E. S. Guzman
Barron^^^ that "... the complexity of the regulating mechan-
isms that link fermentation to respiration diminishes as the
cells go down the phylogenetic scale." Analysis of the onto-
genetic data leads to the same conclusion. ^^* In particular,
a study of the ontogenesis of carbohydrate metabolism in the
brain of birds and mammals shows that the metabolism of
the brain has evolved from being anaerobic to being aero-
bic. ^^^ This may be confirmed by the resistance of embryos
and new-born animals to anoxia, a resistance which dimin-
ishes considerably as the animal becomes mature. It has also
been shown that as the animal becomes older the oxidative
processes in the brain become more intense while anaerobic
glycolysis becomes less intense. N. Verkhbinskaya^^* made a
direct study of the intensity of the respiratory and glycolytic
processes in the isolated brains of cyclostomes, selachians,
sturgeons and bony fishes, amphibians, reptiles, birds and
mammals. In this way she was able to show that in the brains
of the lower, cold-blooded animals the intensity of anaerobic
glycolysis is great, while oxidative respiration only occurs to
a relatively slight extent. In warm-blooded animals the
relationship between the intensities of respiration and glyco-
lysis in the brain seems to be reversed. Respiration increases
significantly while glycolysis decreases. This led the author
to suggest that during the phylogenetic development of
animals there had been a change from the predominantly
anaerobic type of energy metabolism in the brain to the
oxidative type.
Thus, intensive comparative study of the metabolism of
contemporary organisms shows that, though the conditions
of existence on the Earth are different now from what they
were when life first arose, nevertheless we find, in any con-
temporary representative of the living world, the relics of a
primitive organisation which has been inherited from the
first organisms and which is, therefore, now common to all
the inhabitants of the Earth. These are: in the first place,
heterotrophy, the ability to use organic substances as sources
of the energy and of primary structural materials needed
for the synthesis of the components of protoplasm ; in the
ENERGY METABOLISM 437
second place, the anaerobic method of degrading these sub-
stances.
As the conditions of existence changed so, in the course
of evolution, metabolism became more highly developed. Its
primary mechanism became encrusted with more and more
new ' accessories ' which were different in different organ-
isms, but the basic organisation common to all living matter
remained as before. A study of this may therefore help us
to some extent to judge of the external conditions which
prevailed at the time when life first appeared, and of the
ways by which it arose.
The main, and perhaps the sole sources of organic nourish-
ment for the first living things would seem to have been
hydrocarbons and their various derivatives which had been
formed on the surface of the Earth. The reserves of these
substances, though they may have been supplemented to
some extent, were, in any case, very limited. In the mean-
while the growth and multiplication of organisms led to a
greater and greater consumption of organic materials. In
part they entered into the composition of living bodies, but
an even greater quantity was broken down, degraded, during
destructive metabolism.
Thus, the reserve of organic substances in the external
medium available for the nourishment of the first organisms
must, all the time, have been diminishing in quantity and
becoming qualitatively simpler. This disappearance intensi-
fied the struggle for existence and was a potent factor in the
later evolution of the original organisms, inducing further
integration and complexity in their internal chemical organ-
isation. But if the evolution of living things had always been
confined to heterotrophic means of nutrition, then, sooner
or later, the process must have attained its final conclusion
with the complete annihilation of all organic nutrient ma-
terial and the destruction of all living things.
This stimulated the organisms in their struggle for exist-
ence, in the process of selection and adaptation to the new
conditions of life with ^vhich they were faced, to elaborate
within themselves new forms of metabolism which would
enable them, not merely to assimilate exogenous organic
materials as rationally as possible, but also to use other means
438 FURTHER EVOLUTION
to obtain energy from the environment and to assimilate the
simplest forms of carbon compounds.
Photochemical reactions.
The most powerful and inexhaustible source of energy on
the surface of the Earth is solar radiation. As we showed
above, the chief photochemical activity on the primaeval
Earth must have been that of short-wave ultraviolet radia-
tions which decompose water, in particular, to hydrogen and
oxygen in the upper layers of the atmosphere. Although the
hydrogen was constantly escaping from the atmosphere into
space the amount of oxygen thus liberated by inorganic
means was very small ; in any case it was not great enough
to account for the transition of the atmosphere from its
original reducing state to an oxidising state. This was because
the development of even small amounts of oxygen must
immediately have led to the formation of an ozone screen
which prevented the access of short-wave ultraviolet radia-
tions to the lower layers of the atmosphere.
The radiations which fell in large amounts on the first
organisms must therefore have been of longer wavelength,
but these, as is well known, cannot by themselves bring
about such reactions as the photolysis of water. Nevertheless,
it was long ago established in a number of photochemical
studies^" that the energy of visible light can also be used
for carrying out oxidoreductive processes in the presence of
photosensitisers, especially organic pigments, capable of
absorbing such light. According to A. Terenin^^* the mole-
cule of pigment which absorbs the light dissociates into two
radicals and acquires a very high degree of chemical reactiv-
ity which enables it to receive or give up an electron or a
hydrogen atom and thus to bring about oxidoreductive pro-
cesses which could not come about spontaneously in the dark
without the addition of the supplementary energy of light.
If organisms possessed such sensitisers then, even without
the help of complicated supplementary chemical mechanisms,
they could rationalise their heterotrophic metabolism by a
more complete oxidation of the organic substances available
to them in the external medium.
PHOTOCHEMICAL REACTIONS 439
The pigments which assumed the role of such sensitisers
in the original organisms may have been porphyrins. As we
showed in Chapter V, these substances, and metallic deriva-
tives of them, arose in the waters of the hydrosphere as a
result of purely organic-chemical, abiogenic synthesis, even
before the origin of living things. The first organisms could
therefore obtain them ready made, directly from the sur-
rounding medium, and it was only during the course of the
further development of life that there arose the necessity
to synthesise them from such simple metabolic products as
succinic and oxalic acids and glycine, always supposing that
the presence of porphyrins was beneficial to the organisms
of that time, giving them an advantage in the struggle for
existence.
If what has been suggested is true, we must suppose that
porphyrins, or some similar compounds, represent one of
the earliest components of living matter, along with amino
acids, nucleotides, etc. This is suggested by their extremely
extensive distribution in living nature, their presence in all
contemporary organisms without exception.
The classical researches of M. Nencki^^^ on the chemical
nature of haemoglobin and chlorophyll revealed a striking
similarity between these important pigments of the animal
and vegetable kingdoms and showed that both these king-
doms w^ere derived from ancestors which already possessed
porphyrins as necessary components of their protoplasm. This
was later established for microbes with a more primitive
organisation.
Contemporary data on the finding of porphyrins in the
most diverse representatives of the living world are discussed
in great detail in the review of R. Lemberg and J. W.
Legge.^^° We reproduce here a summary of the occurrence of
haemoglobin in the animal kingdom borrowed from this work
(Table 4). Chlorophyll is equally widely distributed in the
plant world. All higher photosvnthetic organisms contain it,
while in the lower ones we find derivatives of porphyrin
similar to chlorophyll (bacteriochlorophyll) or compounds
derived from porphyrin which have a structure similar to
that of the bile pigments (phycocyanin and phycoerythrin).
In tunicates, which are very ancient and primitive organ-
440
FURTHER EVOLUTION
Table 4. Biological Distribution of Haemoglobins
Phylum
Pigment
Examples
Protozoans
Haemoglobin in
cytoplasm
Ciliate paramecia
Nematodes
Erythrocruorin
in body cavity
Myohaemoglobin
in body wall
Several species of Ascaris, intestinal
parasitic worm in mammals. Two
pigments different in character
Annelids
Erythrocruorin
in plasma
Erythrocruorin
Chlorocruorin
in plasma
Scattered throughout phylum, e.g.
Arenicola, the lug worm, or Lum-
bricus, the earth worm
Several species of order Polychaeta,
e.g. Glycera, the blood worm
Several species of order Polychaeta,
e.g. Spirographis, a marine worm
Arthropods
Crustaceans
Insects
Erythrocruorin
in plasma
Found in several species, e.g. Daphnia,
water flea, class Branchiopoda and,
e.g., Ernoecera, parasite in fish, class
Copepoda
Erythrocruorin
in plasma
Chironomus, midges (order Diptera)
Molluscs
Erythrocruorin
in plasma
Erythrocruorin
in corpuscles
Myohaemoglobin
Planorbis, fresh water snail (order
Gastropoda)
Area, a mussel (order Lamellibranchi-
ata)
Busycon, a whelk (order Gastropoda).
Pigment in heart and radula muscles
(haemocyanin in circulation)
Echinoderms
Erythrocruorin Thyone, sea slug (class Holothiiroidea)
Chordates
Protochordates
Vertebrates
So far, neither haemoglobin nor myo-
haemoglobin reported present in
members of this subphylum. Red-
field reports absence of haemoglobin
in Amphioxus
Haemoglobin
in corpuscles
Myohaemoglobin
Present throughout, including Lam-
petra (suborder Cyclostomata)
Probably present throughout, in lower
orders, e.g. Pisces, Amphibia, and
Reptilia, mostly in heart muscle
PHOTOCHEMICAL REACTIONS 44I
isms, there has been found vanadium-haemochromogen
which is also similar to bile pigments."^
Porphyrin derivatives are extremely widely, perhaps uni-
versally, distributed throughout the living world, especially
the iron-porphyrins which play a part in the structure of
living protoplasm as the prosthetic gioups of various enzymes.
It may be confidently asserted that there is no organism in
which such catalysts have been looked for and not found.
According to Lemberg the earliest of such enzymes must
have been hydrogenase, which catalyses the reaction of reduc-
tion by molecular hydrogen based on the following element-
ary process^ *^:
H. > 2H+ + 2e
This enzyme participates in the metabolism of such typical
heterotrophs and anaerobes as the bacteria which carry
out butyric acid fermentation (Clostridia)."^ In them this
enzyme can only manifest its activity in the complete absence
of free oxygen. Hydrogenase has also been found in Esch.
coli,^^'^ in methane bacteria, in Azotobacter, in purple sidphur
bacteria and in the organisms which reduce sulphur com-
pounds to hydrogen sulphide."^ H. Gaffron"** established
that it plays a part in the reduction of cOo by green algae
in the dark. According to E. A. Boichenko"' this enzyme is
also present in the cells of higher plants. Thus we have
evidence of the participation by hydrogenase in the metabol-
ism of the more primitive anaerobic heterotrophs as well
as in that of chemo- and photosynthetic organisms.
The other porphyrin-containing enzvmes are mostly cata-
lysts activating aerobic reactions in which free oxygen and
hydrogen peroxide take part. We are referring to catalase
and peroxidase and also to cytochromes and cytochrome
oxidase.
Naturally the role of these enzymes is especially great in
living creatures which did not arise and develop until the
atmosphere of our planet had been enriched with gaseous
oxygen, until the respirator)^ process came into being.
The finding of cytochrome a by M. Ishimoto and col-
leagues"* in the obligate anaerobe Desulfovibrio desulfiiri-
cans is of particular interest in this connection. It allows us
442 FURTHER EVOLUTION
to suppose that cytochromes arose in organisms which were
living under conditions in which the atmosphere was still
in its primary, reducing state. In these they might have taken
part in anaerobic oxidation-reduction reactions. Only after
the appearance of free oxygen did they assume the character
of typical aerobic mechanisms.
All the reactions listed, which are carried out by iron-
porphyrin enzymes, take place in the dark and therefore no
use is made in them of the important property of porphyrins
which is associated with their colours, with their ability to
absorb light.
We can now understand this quite well, for the iron-
porphyrins in organisms practically never have a photo-
sensitising effect. It is only in the case of cytochrome c that
there has recently been found a very weak activity which
helps to explain its oxido-reductive transformations.^*^
Unlike the iron-porphyrin complexes, porphyrins which
are not combined with metals and, especially, magnesium-
porphyrin complexes, do not have the properties of ordinary
catalysts acting in the dark but are able to carry out photo-
sensitising and photocatalytic activities. The mechanism
whereby iron-porphyrin complexes participate in biologically
important catalytic processes is based on a reversible oxido-
reduction of the central atom of iron, which takes place in
the dark. The researches of A. A. Krasnovskii and his col-
leagues have shown that magnesium-porphyrin complexes,
bacteriochlorophyll and the chlorophyll of higher plants, and
even porphyrins without metals (e.g. haematoporphyrin) can
be reversibly reduced (accepting an electron or hydrogen)
only when they absorb a corresponding quantum of light. ^•'°
When this happens the photocatalytic transfer of an electron
or of hydrogen, unlike ordinary catalytic processes occurring
in the dark, leads to a raising of the energy level of the
products of the photoreaction ; it, so to speak, ' puts into
store ' a part of the absorbed energy of the light in a very
easily mobilised form.^^^
Thus, the mere presence of these porphyrin pigments in
the primaeval organisms enabled them to use in their vital
processes not only the readily available energy of exogenous
PHOTOCHEMICAL REACTIONS 443
organic compounds, but also a supplementary source of
energy, namely light.
In the first period of the existence of life, while there were
plenty of organic compounds, which had arisen primarily,
in the external medium, light, as a source of energy, cannot
have been of decisive significance for the organisms. How-
ever, as the ready-made organic materials disappeared and
the deficiency of them in the external medium became more
marked, so a greater and greater advantage in the struggle
for existence accrued to those organisms which were in a
position to use the porphyrins present in them not only as
catalysts of reactions occurring in the dark, but also as photo-
sensitisers.
In this way they were able to use light as a supplementary
source of energy. The most important result of this was to
enable the first coloured organisms, without undertaking
any considerable reconstruction of their already existing
organisation, to rationalise their heterotrophic metabolism
fundamentally by using exogenous organic substances far
more economically.
Ordinary heterotrophs have to transform a considerable
proportion of the organic substances which they obtain from
the external medium into waste products which cannot be
used further. Only thus can they mobilise the energy bound
up in these substances ^vhich is indispensable for synthesising
the components of protoplasm. By contrast, the first coloured
organisms used the * extra ' energy of light for this purpose
and were thus freed from the need to waste exogenous organic
substances.
This may be understood more clearly by reference to a
study of the metabolism of the contemporary pigmented
bacteria which were discovered quite a long time ago by
T. W. Engelmann."- It has been shoAvn by numerous spectro-
scopic and chemical studies that these organisms contain
considerable amounts of magnesium-porphyrin derivatives,
similar in their chemical nature to chlorophyll a/^^ while
some of them have also been found to contain free por-
phyrins. By virtue of these the bacteria can absorb the
visible radiations of sunlight and use their energy for meta-
bolism. A particular example of such organisms is provided
444 FURTHER EVOLUTION
by the purple bacteria Athiorhodaceae.^^'^ Externally, from
the point of view of its over-all balance, their metabolism is
of the ordinary heterotrophic type. In light they can be
cultivated under anaerobic conditions but the solution in
which they grow must contain organic substances (e.g. butyric
acid or other analogous compounds). As the mass of the
bacteria increases so the quantity of exogenous organic sub-
stances in the surrounding medium decreases correspond-
ingly, but the bacteria also discharge a small amount of
gaseous CO2 into the atmosphere.
The whole difference between the Athiorhodaceae and
heterotrophs which can grow equally well in the dark or in
the light, is that in the light the Athiorhodaceae can use
almost all (90 per cent or more) of the exogenous substances
for increasing their mass. The only ' waste product ' is CO2
which forms only a few parts per hundred of the organic
substances used in the growth and development of the
bacteria. If we compare this with the outlay of organic
substances by ordinary heterotrophs (metabolising in the
dark), in which this dissipation consumes the lion's share of
the nutrients, we shall see how far more rational is the use
of exogenous organic materials by the Athiorhodaceae owing
to their having acquired the ability to use the energy of sim-
light.
As we have already said, on over-all balance, the Athiorho-
daceae may be regarded as heterotrophs requiring organic
substances from the external medium ; but from the point
of view of their internal biochemical mechanisms, these
bacteria already approach the photoautotrophs. Like all
other organisms, they can fix atmospheric co, but in doing
so they make use of the increased energy of the light-absorb-
ing pigments. Thus the Athiorhodaceae carry out a photo-
catalytic transfer of hydrogen, reducing co, and oxidising
the exogenous organic substances. J. W. Foster^" succeeded
in observing this in the case of the oxidation by these bacteria
of secondary alcohols into ketones. As these do not enter
into the general metabolism they accumulate in the external
medium and can therefore easily be estimated. In other cases
such waste products are not formed and the whole metabol-
ism is directed to the synthesis of bacterial protoplasm. ^°
156
PHOTOCHEMICAL REACTIONS 445
Other pigmented bacteria carry out their metabolism
along the same lines, but in them hydrogen sulphide, rather
than organic substances, acts as a hydrogen donor for the
reduction of CO2. These are the so-called purple and green
sulphur bacteria {Thiorhodaceae). They were discovered
long ago in small bays and lagoons of sea water, well exposed
to the sun, in places where the bacteria had access to hydro-
gen sulphide. It was later shown that they are widely
distributed in the soil and also in slimy pools of fresh and
salt water/^''
The very interesting researches of van NieP^* on Thio- .
rhodaceae showed that, in the light, these bacteria can
oxidise hydrogen sulphide in the complete absence of free
oxygen but with the simultaneous absorption of co, in
amounts corresponding stoichiometrically to an equation,
which, for purple sulphur bacteria, is as follows:
H2S -f 2HoO + 2C02-^2CH20 + H2SO4
That for green sulphur bacteria is :
CO2 + SHaS-^CHaO + H2O + 2S
for these latter bacteria can only oxidise UnS as far as sulphur.
According to van NieP^^ the process occurs as follows.
Owing to the presence of porphyrin pigments the Thio-
rhodaceae absorb sunlight and use its energy for the photo-
lysis of water according to the equation
H2O + hv->H + OH
The hydrogen of the water reduces CO2 and transforms it
into the carbon skeletons of the substances of which the
organism is composed (represented schematically in the equa-
tions by CHoO).
According to van Niel the process of photosynthesis in
green plants is analogous with that described for Thio-
rhodaceae. Here also the agent which directly reduces co, is
the hydrogen of water. The only difference is that the
hydroxyl radicals liberated by photolysis are not used up in
oxidising some hydrogen donor (HoS or some organic com-
pound) within the organism. Owing to the presence of
446 FURTHER EVOLUTION
specific supplementary mechanisms in green plants they are
transformed into hydrogen peroxide which is broken down
by catalase to liberate molecular oxygen, thus enriching
the surrounding atmosphere with this gas. Van Niel"" gives
the following scheme to clarify this difference between photo-
synthesis in bacteria and in green plants (Fig. 37).
Photochemical
Dark
reactions
\ ^^E"OH
General
Specific
H,0 '■'^^^ <
Pigment
Enzymes
-K^ "ml
"All ''''
->^ AH,
-*A^'A"+H,0
-K^ CH2O+H2O
-^ CO,
Fig. 37. Scheme of the reactions involved in photo-
synthesis by bacteria and green plants (after van Niel).
In this diagram the symbols e' and e" denote factors
preventing the recombination of the hydrogen and hydroxyl
radicals formed during photolysis. Factor e' directs the
hydrogen to the reduction of CO2 (to CHgO) to an equal extent
in both the bacteria and green plants.
In the bacteria factor e" transfers the hydroxyl radicals
to the appropriate hydrogen donor, indicated by the symbol
AH2;, which may be H2S, thereby splitting off water from it
and leading to the formation of the product of oxidation, a,
e.g. sulphur. In green plants the factor e" transfers the
hydroxyl radicals to a special mechanism which transforms
them to O2 and water via H2O2.
Certain doubts have been expressed by photochemists as
to whether water can be photolysed directly by visible light.
Nobody has succeeded in bringing about this photolysis in
model experiments although various pigments have been
used as photosensitisers.
However, even if we admit that, in van Niel's scheme, the
photolysis of water is a somewhat speculative explanation
of the reversible, photochemical transfer of hydrogen or an
electron by means of the energy of the light absorbed by the
PHOTOCHEMICAL REACTIONS 447
system, this scheme will still retain its significance. It demon-
strates very clearly ^vhat is the essentially new factor in the
development of photosynthesis in the form in which we know
it to-day in green plants. What is new is mainly concerned
with the giving off of molecular oxygen into the surrounding
atmosphere.
The more primitive pigmented organisms had chemical
mechanisms which allowed them to use, as the primary
hydrogen donors in photosynthetic reactions, only the most
readily available or ' active ' donors such as, for example,
organic compounds, or such inorganic substances as hydrogen
sulphide or molecular hydrogen. As examples of organisms
which have retained this relatively simple photosynthetic
organisation we may take the purple and green bacteria
which were mentioned above.
However, during the progressive evolution of the earliest
photosynthetic organisms their internal organisation became
both more closely knit and more elaborate, tending towards
the creation of mechanisms enabling them to use wider and
wider selections of substances as hydrogen donors. This
course of development inevitably led to the inclusion in the
photosynthetic reaction of the more ' difficult ', but also more
ubiquitous hydrogen donor, water. The oxygen of the water
was then liberated in molecular form.
Some contemporary organisms are interesting in that their
metabolism retains features of a more primitive organisation
of the photosynthetic processes, though the ability to give off
the molecular oxygen of water is already manifest in them.
They seem to be intermediate links in the chain between
the earliest photosynthetic organisms and the highly organised
photoautotrophs.
An example of an organism of this sort is the green alga
Scenedesmus, the metabolism of which has been studied in
detail from this point of view by H. Gaffron."^ Under
normal conditions this alga, like all other green plants,
carries out photosynthesis accompanied by the giving off of
oxygen. However, if it is kept for an hour or more under
anaerobic conditions and then placed under relatively weak
illumination in an atmosphere of hydrogen or nitrogen with
cOo, its metabolism will be substantially changed. Under
448 FURTHER EVOLUTION
these conditions it, as it were, reverts to a more primitive
form of photosynthesis, reducing CO2 by means of molecular
hydrogen or endogenous, organic hydrogen donors. Natur-
ally no oxygen is given off under these circumstances.
Thus, under these conditions Scenedesmus reverts to a
form of metabolism similar to that which we described above
as occurring in the heterotrophic Athiorhodaceae or in the
autotrophic hydrogen bacteria. In the latter case the over-all
result of the photosynthesis carried out by Scenedesmus may
be expressed by the equation
2H2 -I- C02->CH20 -f H2O
In this reaction, which involves the oxidation of molecular
hydrogen, the enzyme hydrogenase plays an important part,
being adaptively activated under reducing conditions. When
oxygen is present, or when the illumination is more intense,
the activity of the hydrogenase is destroyed and the alga
reverts to its normal metabolism, photoautotrophic absorp-
tion of CO2 and production of O2.
The formation of free oxygen.
The period when autotrophic photosynthesis was coming
into being and leading to the formation in the atmosphere
of ever greater and greater amounts of molecular oxygen,
liberated from water by means of the energy of the long-wave
components of sunlight, was one of the most remarkable
periods in the whole history of our planet. It was a critical
time, separating the two important epochs of the history of
the surface of the Earth, the reducing and the oxidising
epochs.
This period is of especial interest from the point of view
of the student of the evolution of metabolism because it was
just in this transitional epoch, when the external conditions
of life were radically altered, that there arose numerous and
diverse new forms of metabolism, there occurred what might
be described imaginatively as a tense search for new paths
for the process of life. Later on, when this revolutionary
period of ' Sturm und Drang ' had become a thing of the
past, when more or less constant oxidising conditions had
FORMATION OF FREE OXYGEN 449
been established in the atmosphere, some of these new paths
became the broad highways for the development of most of
the living things on our planet, while others degenerated
into narrow side alleys along which only a very few groups
of specialised organisms pursue their metabolic activities.
Let us try to imagine the circumstances which prevailed
on the surface of the Earth at the time which we have been
describing, about 700 or 800 million years ago. The exogen-
ous organic substances which had originally been formed,
and which could serve as nutrients for the heterotrophic,
anaerobic organisms which then inhabited the Earth, had
largely disappeared. The atmosphere contained an abun-
dance of carbon dioxide, hydrogen, methane and other
gaseous substances, which had been formed by various fer-
mentative processes. Dissolved in the water of the seas and
oceans there were ethyl alcohol, various organic acids and
the waste products of anaerobic metabolism which were of
no further use. Partly in solution and partly in the deposits
there were carbonates and a number of reduced inorganic
substances such as ferrous oxide; some of these had remained
in their original state and some, such as ammonia and hydro-
gen sulphide, had arisen biogenically.
All these substances were relatively inaccessible to the
living things of that period in the absence of free oxygen.
Only the earliest photosynthetic organisms, which had already
arisen by that time, were able to make extensive use of, and
almost monopolise, the diverse organic residues of fermenta-
tion and such substances as methane, h, and H2S as hydrogen
donors for reduction of the CO2 which they fixed, and for
building up their structural components. Thanks to this
they must have obtained a considerable advantage in the
struggle for existence at that particular time. Their rapid
development and evolution, which occurred as a result of
this advantage, provided a basis for the emergence of the
extremely complicated and efficient metabolic mechanisms
which are characteristic of present-day photoautotrophs.
However, in the very process of their development, these
organisms began to enrich the atmosphere with molecular
oxygen. This entailed a profound alteration in the course
of the evolution of life as a whole on our planet. The appear-
29
450 FURTHER EVOLUTION
ance of molecular oxygen provided a theoretical possibility
for even the colourless heterotrophs to rationalise their
metabolism and to make use of substances which could not
be used before by ordinary anaerobic heterotrophs. Under
these circumstances the practical realisation of this possibility
only required very small additions to the previously existing
metabolic mechanisms of the organisms. In particular, as
we pointed out on p. 430, the transition from obligate to
facultative anaerobiosis could be brought about simply by
an alteration in a single link in the long chain of glycolytic
degradation. This involved the replacement of anaerobic
decarboxylation of pyruvic acid by its oxidative decarboxyla-
tion and the reaction whereby acetyl-coenzyme A is formed
proceeded in accordance with the equation with which we
are already familiar :
CH3C0.C00H + CoA + |o2->acetyl-CoA -f CO2 + n^o.
Thus, such facultative anaerobes as Esch. coli and Strep,
faccalis can, under aerobic conditions, not only break sugar
down to lactic acid, but can also oxidise it to acetic acid,
which is considerably more advantageous from the point of
view of acquiring energy. In the absence of oxygen they
form, as well as acetic acid, reduced products such as ethyl
alcohol which are useless to these organisms under the postu-
lated conditions. On the other hand, the acetic acid bacteria,
advancing even further, became confirmed aerobes ; they
can oxidise not only sugar, but also ethyl alcohol to acetic
acid, thus putting it back into circulation in their energy
metabolism and mobilising the energy of this waste product
of fermentation which was previously of no use whatsoever
to heterotrophs.
The line of evolution which began in this way seems to
have been the outset of the development of various faculta-
tive anaerobes which effect many so-called oxidative fermenta-
tions."^
Chemosynthesis.
It is our opinion that it was in this transitional period
that metabolism became differentiated, and that such special-
CHEMOSYNTHESIS 45I
ised gi'oups of organisms as the chemoautotrophs made their
appearance. It was just at this intermediate period, between
the prevalence of reducing and oxidising conditions, that
there first arose the possibility, in principle, of oxidising the
reduced inorganic substances of the crust of the Earth on an
extensive scale by means of molecular oxygen. At the period
we are dealing with, when free oxygen was beginning to be
formed, these oxidative reactions must have been occurring
at, literally, every point on the surface of the Earth, for oxidis-
able substrates were present everywhere. However, when
these reactions took place inorganically they proceeded,
relatively speaking, very slowly and the energy which they
liberated was lost, being dissipated in the form of heat.
When there was an acute shortage of exogenous organic
compounds those organisms which, during their evolution,
had become able to include in their metabolism those re-
actions whereby inorganic materials are oxidised, and which
had formed in their bodies catalytic mechanisms which
hastened these processes and mobilised the energy derived
from them for biosynthesis, certainly had a great advantage
in the struggle for existence. Their position was therefore
secured by natural selection and they were later able to
develop extensively.
At present we usually find organisms capable of a chemo-
autotrophic way of life under natural conditions in just those
places where the reducing substances of the depths, emerging
into the daylight, encounter the molecular oxygen of the
atmosphere. For example, reduced compounds of sulphur
are easily formed in nature wherever anaerobic conditions
prevail. Tremendous amounts of hydrogen sulphide accumu-
late in the seas and oceans in places where the water is stag-
nant owing to differences in salinity between the surface and
deep layers. Considerable amounts of hydrogen sulphide are
also concentrated in the water of the petroleum-bearing
strata, and also on the surface of the Earth under conditions
which lead to the anaerobic decomposition of proteins.
Wherever hydrogen sulphide passes from a medium where
the conditions are reducing into one where they are oxidis-
ing, there we always find the development of thionic or
sulphur bacteria. ^^^ Similarly, the nitrifying bacteria carry
452 FURTHER EVOLUTION
out their activities at the boundary of a region where
ammonia is being formed anaerobically and one where it
comes into contact with the molecular oxygen of the air.
This may be observed in the soil, in sea water and in bogs."^
The iron bacteria, which oxidise ferrous to ferric salts,
develop especially luxuriantly where rich sources of iron
emerge on to the surface of the Earth. "^
At the present time very large amounts of hydrogen are
given off from the depths of the Earth and from wherever
the anaerobic decomposition of carbohydrates and proteins
is taking place. ^'^^ Bogs, especially, produce a considerable
amount of so-called marsh gas which contains hydrogen and
methane. In deeper waters the oxygen which penetrates into
them oxidises these gases as a result of the activities of hydro-
gen and methane bacteria and this often leads to the complete
disappearance of oxygen from the hypolimnion.^"
Nowadays the chemoautotrophs play a very important part
in the circulation of materials. Practically all the processes
occurring under natural conditions leading to the oxidation
of reduced compounds of nitrogen and sulphur (and also
of hydrogen, methane and, to some extent, iron) are associ-
ated with the vital activities of the appropriate micro-
organisms.
Table 5 is taken from S. Kuznetsov.^^^ It shows the
reactions carried out by the chemoautotrophs and the
organisms related to them. The equations given are, of
course, only those for the over-all reactions. The chemical
mechanism of these reactions has, as yet, only been very little
studied. At first it was believed that the metabolism of the
chemoautotrophs was very primitive."* However, as the
study of this field progresses, it becomes clearer and clearer
that it is far more complicated than the metabolism of ordin-
ary heterotrophs."^
A particular illustration of the great metabolic activity and
complexity of the chemoautotrophs is their ability to syn-
thesise various vitamins and growth factors. For example,
according to D. J. CKane,^''" T. thiooxidans can synthesise
thiamine, riboflavin, nicotinic and pantothenic acids, pyri-
doxine and biotin, i.e. almost all the members of the vitamin
B complex. This points, first of all, to a very great complexity
3
O
s
is
3 C
Q to
!- !-
CO
Bacillus hydrogenes
Bac. pycnotica
Process observed but little
studied
Cultural characteristics
resembling Bac. saussurei
Vibrio desulfuricans
Melhanobacterium omelianskii
Perfiliewia
Bac. methanicus
Methanomonas methanica
Proactinomyces oligocarbo-
philus
Nitrosomonas
Nitrobacter
Chromatium
Thiobacillus thiooxydans
Thiobacillus denitrijicans
Thiobacillus denitrijicans
Thiobacillus thioparus
Leptothrix ochracea
Spirophyllum ferrugineum
Gallionella ferruginea
<3
o --r^ o o o
o o o o o
q^ o ^^ c^ ^~^
o" 2, o" j>. 4^
1 ^^ ' ' 1
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o o
9, q
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CO I>-
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o o o o o o
ITS q irp q_ q^ q^
-H ei 00 O CO o'
Tfl -H rt O O ^
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q^
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f~l
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tot „ .£
+ ., + + + +
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ffi ?, ffi ffi ffi ffi
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u u
+
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o
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CD oo ^ «=
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i„0 K „t^ «5 + 7
2.^ +S "to t
+ + d" § 9. ^^. q.
^" ^ + CD Z Z
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Source of energy
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0
t«
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32o
0
454 FURTHER EVOLUTION
in the metabolism of these organisms, in that the synthesis
of these vitamins requires the participation of a large number
of strictly co-ordinated biochemical reactions. Secondly, it
points to a connection between this metabolism and the
glycolytic and oxidative transformations of carbohydrates, in
that vitamins of the B group catalyse these reactions through-
out the whole living world.
As we have already shown, the metabolism of the chemo-
autotrophs is, in fact, based on the same glycolytic mechan-
isms as that of the heterotrophs. In the chemoautotrophs,
however, there are superimposed on these mechanisms
supplementary chemical adaptations, enabling them to use
energy derived from the oxidation of inorganic substances
for synthetic processes. These inorganic oxidations them-
selves may be found in the metabolism of some ordinary
heterotrophs. For example, Esch. coli can oxidise hydrogen,
many mycobacteria can nitrify, typical heterotrophs oxidise
sulphur, thiosulphate, etc.^^^
In addition, as R. HilP^^ rightly pointed out, the mechan-
ism of fixation of CO2 is identical in chemoautotrophs and
in ordinary heterotrophs. The only difference is that the
heterotrophs cannot use the energy and the reducing sub-
stances formed during the oxidation of mineral substances
for the assimilation of cOo. They lack the necessary mechan-
isms for this. However, the appearance of these mechanisms
on top of the finished organisation of the rest of the meta-
bolism was not too complicated and was easily assured by
natural selection in the epoch which we are considering, as
they enabled the organisms to escape from the actual bitter
struggle for organic substances.
The great systematic diversity of the chemoautotrophic
groups and the similarity between some of their individual
representatives and various heterotrophs (with which many
of them are connected by transitional organisms) convinces
us that chemoautotrophy arose on more than one occasion,
and that its initial and exuberant development dates from
a time when there already existed a great diversity of organic
forms. This development was made possible by the special
conditions of the period under discussion and particularly
by the shortage of organic nutrients and the extensive avail-
PHOTOSYNTHESIS 455
ability of inorganic sources of energy. However, when condi-
tions on the surface of the Earth became oxidising these
sources were rather quickly exhausted and were only re-
plenished comparatively slowly from the deeper layers of the
crust of the Earth. On the other hand, the balance of organic
substances in the biosphere became more and more positive
owing to the appearance and quick development of photo-
autotrophs. Nowadays, although chemoautotrophs play an
important part in the circulation of sulphur, nitrogen, etc.,
they have long ago been relegated to a secondary position
as producers of organic substances by green plants, and only
constitute a fraction of one per cent, of the general mass of
living things.
Photosynthesis .
Undoubtedly the highway of autotrophic development was
photosynthesis as we see it now in gi^een plants/" The use
of water as a hydrogen donor in photosynthetic organisms
was a tremendous advance in the development of biochemical
systems which linked the light-induced stage of the process
with the cycles of reactions and which brought about the
gradual reduction of CO2 and the formation of molecular
oxygen.
However, the taking of this step required the prolonged
evolution of organisms which were already rather highly
developed and which possessed a large arsenal of diverse
metabolic mechanisms. Our knowledge of the photosynthetic
apparatus of contemporary plants convinces us that this must
be so. It is extremely complicated and, in spite of much
research, it is still far from being fully worked out.
In order to give a general picture of what happened, we
may make the following analogy although, of course, it must
not be pushed too far. We may take a motor-car engine
as our example of a complicated system which carries out a
particular job. The work of the engine does not depend
exclusively on its essential component, the cylinder block.
It also depends on a number of accessory mechanisms, some
of which are themselves complex, each with its own specific
task, e.g. the preparation and delivery of the combustible
456 FURTHER EVOLUTION
mixture, the production of a high-voltage spark to explode
the mixture, cooling, lubrication, transmission, the regula-
tion of speed, etc. If the engine is to run smoothly, not only
must each of these systems function well, they must also
be well co-ordinated in both time and space. The spark from
the plugs must occur when the piston is in a particular
position in the cylinder ; the mixture must enter the cylinder
at the appropriate moment, etc.
Similarly, in the photosynthetic apparatus of a plant, we
are not dealing with one single chain of chemical transforma-
tions but with a number of cycles of biochemical reactions,
whole aggregates of catalytic and photochemical systems.
Only when they are highly co-ordinated, when they are
continually interacting, can their proper effect be obtained.
This is achieved not only by a definite accurate co-ordination
of the separate reactions in time, but also by their spatial
localisation, the existence of a certain structure in the
photosynthetic apparatus. The photosynthetic enzymes are
' assembled ' on this structure and the products of the photo-
synthetic cycle move over it. Nobody has yet succeeded in
reproducing photosynthesis outside the living cell, in contrast
to alcoholic fermentation which may be observed in a solu-
tion if this contains all the necessary enzymes. This, in itself,
indicates the extreme complexity of the photosynthetic
system.
In the chloroplasts of plants the chlorophyll is concentrated
in minute granules which take the form of flattened cylinders
having a diameter of 05 /a and a thickness of 02 /x. The
granules consist of plates of protein combined with a chloro-
phyll-containing lipid layer, like a sandwich made of two
slices of bread with butter inside."* According to this view
the polar, magnesium-porphyrin nucleus of the chlorophyll
is associated with the protein, while its hydrophobic phytyl
tail is directed towards the lipid layer of the granule.
On such a protein-lipid aggregate there occurs, first of all,
the initial photochemical act which may be provisionally
designated as the ' photolysis of water '. However, in addi-
tion to this ' photolytic ' system, and in parallel to it, there
must be, as in the motor-car engine of which we spoke, other
systems or aggregates taking part in the process of photo-
PHOTOSYNTHESIS 457
synthesis. These may be characterised as follows: (i) The
formation of molecular oxygen ; (2) the dark fixation of
CO2 ; (3) the reduction of CO2 as far as carbohydrates ; (4) the
synthesis of sugars from phosphotrioses ; (5) the formation
of ' active hydrogen ' in the shape of reduced forms of di-
and triphosphopyridine nucleotides ; (6) the formation of
high-energy bonds (ATP) (Fig. 39).
We shall now give a very schematic exposition of the work
of all these aggregates, using, for the most part, the data
published by M. Calvin^" in his address to the Third Inter-
national Congress of Biochemistry held in Brussels.
According to M. Calvin, when light falls on the laminated,
chlorophyll-containing aggregate, it splits off electrons. The
electrons and the remaining positive holes are quickly shared
out over the structure.
According to A. Krasnovskii, V. Evstigneev and their col-
leagues, the photochemical transfer of electrons which
underlies the action of chlorophyll occurs by means of an
intermediate, reversible photoreduction of the pigment. This
supposition is substantially strengthened by the recent
observation in living, photosynthesising organisms, of rapid
spectral variations corresponding with those which occur
during the photoreduction of chlorophyll.^"^ The negative
charges (electrons) which are produced in one way or another
are used for the reduction of phosphopyridine nucleotides
(in system 5), while the positive charges act on water, leading
to its oxidation (in system 1).
The details of the working of system (1) have not yet been
fully elucidated but there can be no doubt whatever that
the molecular oxygen given off during photosynthesis is
derived from water, as was asserted by A. N. Bach (Bakh)^"'^
as early as 1893, and proved experimentally considerably
later by A. P. Vinogradov and R. V. Teis^" in their experi-
ments with isotopes of oxygen. The nearest thing to extra-
cellular photosynthesis is the reaction obtained by Hill, who
showed that, in the light, oxygen is split off from water in
the chloroplast, but only when the surrounding medium
contains such powerful hydrogen acceptors as quinones,
organic pigments and ferric salts. This is necessary in order
to prevent the reaction from occurring in the reverse direc-
458 FURTHER EVOLUTION
tion. It would seem that there is formed, as an intermediate
product during the process of photo-oxidation of water,
either hydrogen peroxide or else an organic peroxide which,
on breaking down, gives rise to molecular oxygen. The oxy-
gen which is formed in this way is mainly given off into the
atmosphere, but part of it is used in the process of photo-
synthesis, especially in system (6).
In green plants the dark fixation of CO2 (system 2) is mainly
carried out by the same mechanisms which operate in
ordinary heterotrophs, namely coenzyme A and phosphate
dehydrogenases. According to M. Calvin the primary accep-
tor of CO2 is ribulose disphosphate, which is obtained by the
phosphorylation of ribulose monophosphate at the expense
of ATP. The formation of ATP occurs in system (6) which
will be discussed below, while the initial ribulose mono-
phosphate is formed in system (4).
Ribulose disphosphate is carboxylated by CO2 with the
help of the enzyme carboxydismutase and the intermediate
product thus obtained, which now contains six carbon atoms,
is broken down to two molecules of phosphoglyceric acid.
This acid is the primary product of the fixation of CO2 by
green plants and is later transformed, in systems (3) and (4),
into various sugars.
In system (3) there takes place the reduction of phospho-
glyceric acid to triose phosphates (glyceraldehyde phosphate
and dihydroxyacetone phosphate). The carrying out of this
reaction requires, in the first place, ' active hydrogen ' which
is supplied in the form of reduced di- and triphosphopyridine
nucleotides which are elaborated in the special system (5).
In the second place it requires ATP which, as we shall see,
is obtained from system (6).
The later transformation of triose phosphates takes place
in system (4) and comprises, in part, their condensation to
hexose disphosphate by means of aldolase (Fig. 38) and partly
the formation of a number of phosphoric esters of various
sugars having four, five, six, seven and ten carbon atoms.
This leads, in particular, to the formation of ribulose mono-
phosphate. According to Calvin this process takes place in
the following order: The hexose (Cg), formed from triose-
phosphates, is broken down (c, and C4). The sugar with the
i
PHOTOSYNTHESIS
459
four carbon atoms (C4) combines with a C3 substance to give
sedoheptulose (c^). By combining with glyceraldehyde phos-
phate (Cg), sedoheptulose monophosphate gives rise to a phos-
phorylated Cio carbohydrate which is broken down by the
enzyme transketolase into two phosphopentoses, ribulose
monophosphate (Cj) and ribose monophosphate (C5).
02(905)
hi/ (quontum)
ITOOOA
polysaccharides
g (hexose)
Fig. 38. Proposed cycle for carbon in photosynthesis
(after Calvin).
Thus, in this process there takes place the transformation
of the various sugars characteristic of the vegetable kingdom
into one another. In the last analysis they are all derived
from phosphoglyceric acid. However, this cycle of reactions
can only run smoothly when there occurs the essential
reaction of the reduction of phosphoglyceric acid into glycer-
aldehyde phosphate. This requires a continuous supply of
reduced pyridine nucleotide and ATP, the former derived
from system (5) and the latter from system (6).
The participation of reduced pyridine nucleotides in the
dark fixation of CO2 in heterotrophs has been extensively
demonstrated in the researches of S. Ochoa."* The experi-
mental material now available shows that hydrogen, which
is mobilised photochemically, is transferred to pyridine
nucleotides by means of pigments which act as photo-
sensitisers.
460 FURTHER EVOLUTION
Thus it is probable that ' active hydrogen ' enters the cycle
of the assimilation of CO2 as reduced forms of pyridine nucleo-
tides which take part in the reaction whereby CO2 is reduced
as far as carbohydrate (system 3).
The elaboration in the chloroplasts (in system 5) of
reduced pyridine nucleotides, using the hydrogen which was
formed in the initial photochemical reaction, has also been
demonstrated in model experiments. In particular, as early
as 1949 A. A. Krasnovsk.il and his colleagues^^' succeeded
in this way in showing that chlorophyll sensitises the transfer
of hydrogen to pyridine nucleotides and to flavines, the
energy of light being accumulated in the products of the
reactions. These authors put forward the hypothesis that it
is just this reaction which links the light-induced stage with
the process of reduction of cOg.""
Somewhat later W. Vishniac and S. Ochoa^*^ shov/ed that,
in fact, isolated chloroplasts, together with homogenates, can
reduce photochemically the pyridine nucleotides which are
associated with the enzymic stages of the assimilation of
CO2. This is confirmed by the finding of various dehydrogen-
ases in chloroplasts.^*^
The methods of formation of high-energy phosphorus
compounds (system 6) in the process of photosynthesis have
still been only very poorly studied, as was rightly remarked
by R. Hill.^*^ It is evident that the cell of the green plant
has a number of mechanisms for carrying out this task, which
it borrows from the metabolic arsenal of enzymes of the
heterotrophs and the chemoautotrophs. Associated with these
mechanisms are the specific pathways of photochemical phos-
phorylation. According to Hill, the energy needed for the
esterification of inorganic phosphate is obtained, in green
plants, by the oxidation of whatever compounds have been
reduced under the influence of light. The energy obtained
by such oxidation is accumulated in high-energy phosphorus
compounds and in this form it enters into the photosynthetic
cycle of reduction of fixed CO2.
The recent work of D. I. Arnon and colleagues^** has
shown that when isolated chloroplasts are illuminated they
can form ATP from ADP and inorganic phosphate ; this
PHOTOSYNTHESIS 461
reaction requires the participation of a number of co-factors,
the most important of which is ascorbic acid.
It is most likely that in the formation of ATP by these
reactions, ' photochemical phosphorylation ' follows a similar
course to oxidative phosphorylation. The initial hydrogen
donor (reduced substance) is photochemically produced
' active hydrogen ' in, for example, the shape of reduced forms
of pyridine nucleotides, while the oxidising agent is oh
formed by the photolysis of water, hydrogen peroxide, or
even molecular oxygen. In this reaction of photochemical
oxidative phosphorylation there probably take part many
of the ordinary respiratory mechanisms (e.g. cytochromes and
flavines) and oxidative cycles (e.g. the tricarboxylic cycle of
Krebs) with which we shall become acquainted in more
detail in our exposition of the mechanism of respiration.
Calculations show that the fundamental reaction of
* raising ' CO2 to the level of carbohydrates requires the par-
ticipation of four electrons and three molecules of ATP, one
of which is expended on the phosphorylation of ribulose
monophosphate before its carboxylation by CO2.
As a synopsis we give here a gi'eatly simplified scheme of
the interactions of the separate aggregates in the general
process of photosynthesis (Fig. 39).
A detailed knowledge of the photosynthetic apparatus of
green plants shows that hardly any of their catalytic mechan-
isms or even of their whole aggregate of mechanisms show
anything which is new in principle. In most cases we find
the very same or analogous mechanisms in various colourless
organisms or in photosynthetic bacteria.
Thus, even before the appearance of green plants, before
the development of the present-day forms of photosynthesis,
these chemical mechanisms existed, but they were scattered
rather than being integrated into a single complex system.
This unification of previously existing mechanisms took
place during the development of the photosynthetic appara-
tus. It could only have been formed during the process of
evolution of organisms on the basis of pre-existing systems
and aggregates.
Continuing our analogy with the motor-car engine, we
may say that, as the history of technology shows, such an
462
FURTHER EVOLUTION
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PHOTOSYNTHESIS 463
engine could only appear on the basis of pre-existing
machines. Before the invention of the cylinder and the
dynamo, even the most ingenious constructor could not have
built such an engine.
The appearance of photosynthesis constituted an extremely
important stage in the process of evolution of life on our
planet. It radically changed all the relationships which had
previously existed. Alongside the formation of oxygen in
the atmosphere there began a rapid increase in the quantity
of organic substances in the biosphere which could once
more be put into metabolic circulation by the old hetero-
trophic methods. It allowed the main current of evolution
to revert to the old channel, with the further development
of organisms adapted to nourishing themselves on organic
materials. The period of acute scarcity of these substances
passed, and there only remained, as a souvenir of it, a small
group of autotrophic organisms capable of chemosynthesis,
which constituted a side branch of the main evolutionary
stream.
The main channels for this stream now became the green
plants (photoautotrophs) and colourless organisms, animals
in particular, w'hich were adapted to the earlier, more primi-
tive heterotrophic habit. However, after the emergence of
photosynthesis, the evolution of even those organisms which
used ready-made organic substances for their vital processes
took place under entirely different biochemical conditions
from those which prevailed before this emergence.
The decisive condition in this regard was the presence of
oxygen in the atmosphere. This allowed a considerable
rationalisation and intensification of the process of mobilisa-
tion of the energy of organic substances. Naturally, this
rationalisation took place on the basis of the same anaerobic
mechanisms on which the energy metabolism of the earlier
heterotrophs had been founded. ^^^ However, in the process
of evolution under the new aerobic conditions, natural
selection guaranteed the survival and further development
of those organisms in which there arose accessory enzymic
complexes and systems of reactions which allowed them to
obtain from the exogenous organic substances far greater
amounts of high-energy compounds than had earlier been
464 FURTHER EVOLUTION
possible. This was made possible by the complete oxidation
of the nutrients by means of atmospheric oxygen.
The origin of respiration.
The accomplishment of this task required the organisation
of two new systems. First, a system for the mobilisation of
the hydrogen which, under anaerobic conditions, had gone
to waste, being given off from the organism in the form of
reduced organic compounds which could not be used any
more (e.g. acids and alcohols), or even in the form of gaseous
products such as hydrogen. Secondly, a system for the activa-
tion of oxygen so that it might be possible to oxidise hydro-
gen to water, to carry out the reaction which occurs when a
mixture of hydrogen and oxygen gases is exploded.
The individual mechanisms of the first system are very
ancient. They were mostly present in the anaerobic organ-
isms. They are the pyridine nucleotides, coenzyme A, etc.,
with which we are already quite familiar. On the develop-
ment of aerobiosis their activity was merely extended to a
number of new products which were absent from the general
scheme of glycolysis. In its essence this scheme of the initial
transformation of carbohydrates was retained unchanged in
aerobes but, at particular places in this scheme, there were
embodied new chains and cycles of reactions the individual
components of which give up their hydrogen to a pyridine
nucleotide or some other analogous acceptor (e.g. a flavine
derivative).
Such places where new cycles have been embodied have
been located exactly in rather primitive facultative anaerobes.
In our earlier discussion of Strep, faecalis and other analogous
microbes, we saw how aerobiosis first arose. Here we were
concerned with the pyruvic acid which was formed in the
process of glycolysis and which, in the absence of oxygen,
underwent anaerobic dehydrogenation and decarboxylation
to form acetic acid, alcohol and lactic acid. In the presence
of oxygen, however, the pyruvic acid was decarboxylated
oxidatively so that the formation of acetic acid was not
necessarily accompanied by the appearance of reduced pro-
ducts (alcohol and lactic acid). In propionic acid bacteria,
RESPIRATION 465
on the other hand, pyruvic acid is not decarboxylated but
combines with CO2 to form oxaloacetic acid. This then under-
goes anaerobic or oxidative transformations.
In higher organisms, capable of respiration, the pyruvic
acid which arises in the ordinary ^vay, by glycolysis, undergoes
both oxidative decarboxylation and condensation with CO2
owing to the action of ^-carboxylase. As a result of this,
from every t^vo molecules of pyruvic acid there are formed
one of acetic acid (as in Strep, jaecalis) and one of oxaloacetic
acid (as in the propionic acid bacteria).
In higher aerobes, however, by contrast to these bacteria,
this is not the end of the matter, and it is just at this point
in their metabolism that there is embodied the new closed
chain of transformations which has been called the Krebs
cycle, or the tricarboxylic acid cycle. ^*®' ^^^ A diagram of this
cycle is given below (Fig. 40).
As we see from the diagram, the original sugar (glucose) is
first transformed into pyruvic acid (the route of this glycolytic
transformation, which is common to all organisms, is not
shown on the diagram). The pyruvic acid is then transformed
into acetic and oxaloacetic acids as was indicated above.
The oxaloacetic acid easily goes over to its enolic form
(hooc.ch:coh.cooh), which condenses with an activated
molecule of acetic acid to give citric acid. This acid is con-
verted first into m-aconitic acid and then into isocitx'ic acid,
which then undergoes dehydrogenation (in this reaction
^.yocitric dehydrogenase and triphosphopyridine nucleotide
take part, the latter taking up the hydrogen). The oxalo-
succinic acid thus formed is decarboxylated and converted
to a-oxoglutaric acid. This acid again undergoes oxidative
decarboxylation to give succinic acid which loses hydrogen
owing to the action of succinic dehydrogenase and becomes
fumaric acid. The fumaric acid combines with a molecule
of water under the influence of fumarase to give malic acid.
Malic dehydrogenase acts on this, bringing about its trans-
formation mto oxaloacetic acid. This brings the cycle back
to the beginning again, as the oxaloacetic acid thus formed
can once more condense with a new molecule of activated
acetic acid so that the whole reaction of oxidative dissimila-
tion of pyruvic acid can be repeated.
30
466
FURTHER EVOLUTION
GLUCOSE
OXALOACETIC
ACID
MALIC
ACID
CIS-ACONITIC
ACID
COOH
I
CH
FUMARIC \ II
ACID
SUCCINIC
ACID
•HjO ''"'' 6 / ^"-^ OXALOSUCCINIC
CO, f CO I ^(^10
COOH ^2 COOH
a-OXOGLUTARIC
ACID
Fig. 40. The tricarboxylic cycle (after Krebs).
RESPIRATION 407
In the course of this cycle all of the three carbon atoms of
the pyruvic acid are oxidised to cOg by means of the oxygen
of water while, at the same time, the hydrogen leaves the
cycle with the help of pyridine nucleotides and the corre-
sponding dehydrogenases. The splitting off of CO2 is brought
about directly by decarboxylases.
Thus we see that the same types of enzymic mechanisms
act here as act in anaerobic metabolism, but the sequence
of reactions is substantially different. An important difference
is that the hydrogen which is liberated is not wasted but is
used to obtain a considerable extra supply of energy by its
oxidation by the oxygen of the air. The intermediate products
arising in the cycle carry it over into other metabolic systems
so that there is established a direct connection and mutual
dependence between the metabolism of carbohydrates, fats,
organic acids and proteins. A particular example is the trans-
formation of keto acids which leave the cycle, by reacting with
ammonia (i.e. by direct amination^") or by transamination,^**
into alanine, aspartic and glutamic acids and the formation
from these of various other amino acids which take part in
the synthesis of proteins, hormones, enzymes, etc.
The incorporation of accessory respiratory transformations
in the chain of glycolytic reactions can take place not only
through the pyruvic acid at the end of the chain, but also
through its first links.
As we noticed on p. 427, even among anaerobic alcohol
producers, e.g. Pseudomonas Undneri, the metabolism may
diverge somewhat from the general scheme of alcoholic
fermentation. In this case hexose-6-phosphate is not further
phosphorylated but immediately enters the path of anaerobic
dehydrogenation, being thereby transformed into 6-phospho-
gluconic acid. This is decarboxylated to a phosphorus deriva-
tive of pentose, which then breaks do^vn to give alcohol and
glyceraldehyde-3-phosphate. This glyceraldehyde-3-phosphate
then enters into the general scheme of alcoholic fermenta-
tion. Among many facultative anaerobes this is used as an
oxidative path. In these there takes place, alongside the
ordinary glycolytic breakdown of glucose according to the
scheme for alcoholic fermentation, the oxidation of glucose-
468 FURTHER EVOLUTION
6-phosphate to 6-phosphogluconic acid with its subsequent
oxidative decarboxylation to pentose-5-phospliate.
As an example we may cite Microbacterium lacticum
which has such an oxidative mechanism. However, in this
organism the complex of glycolytic enzymes still predomin-
ates to such an extent that even in air the formation of
glyceraldehyde phosphate and pyruvic acid mainly follows
the scheme for anaerobic fermentation, while the contribu-
tion made by the direct oxidation of hexose is relatively
small/*^
According to V. A. Engelhardt and A. P. Barkhash""
yeasts, on the contrary, switch over definitely to the oxidation
of hexose monophosphate under aerobic conditions. Moulds
can also oxidise glucose directly and intensively."^ In par-
ticular, Aspergillus niger can, under appropriate conditions,
transform glucose almost quantitatively into gluconic acid
(the so-called ' gluconic acid fermentation '). In this case,
however, the oxidation of glucose occurs without its pre-
liminary phosphorylation, being mediated by the enzyme
glucose oxidase. According to the evidence of P. Kolesnikov"^
an analogous breakdown of hexose without preliminary
phosphorylation plays a predominant part in the respiration
of unicellular green algae (e.g. Chlorella).
From our point of view the obligate aerobe Pseudomonas
fluorescens is of great interest. Nobody has succeeded in
finding in it hexokinase, which brings about the phosphoryla-
tion of hexose before its breakdown to triose phosphates,
while in addition the aldolase, which catalyses this break-
down, is only very weak in these organisms. In Pseudomonas
fluorescens, therefore, the glycolytic breakdown of sugars
is relegated to the background although glyceraldehyde-3-
phosphate and pyruvic acid, which are products of this
process, figure in the metabolism of the organisms. They are
formed by somewhat different means from those of the classi-
cal scheme of glycolysis. W. Wood gives the following scheme
for the oxidative breakdown of glucose in this micro-organism
(Fig. 41).
As may be seen from this scheme, the main means of oxida-
tive transformation in Pseudomonas fluorescens lies through
the direct oxidative dehydrogenation of glucose with its
RESPIRATION
469
transformation first into gluconate and then into 2-oxoglucon-
ate. However, these products are later phosphorylated and
transformed with the formation of numerous compounds, in
particular 5- and 7-carbon sugars (ribose and sedoheptulose).
GLUCOSE —
I
I
i
GLUCOSE-6-PO4
-2H
^ GLUCONATE
+ ATP
-2H
-2H
6-po4-6luconate
-2h/h:o,
^ 2-KETOGLUCONATE
+ ATP
2-KET0-6-PQ,-
GLUCONATE
FRUCTOSE-6-P0,
SEDOHEPTULOSE -
, 7-PO4
?— ,
>' ^,
'4
♦ ATP
GLYCERALDEHYDE-
..< 3-PO4
->- PYRUVATE
^■
FRUCTOSE-1,6-
di-P04
Fig. 41. Pathways in glucose oxidation by
Pse udo m o nas flu o rescens
(after Wood).!^^
But the old metabolic pathway is retained in Pseudomonas
fluorescens and, under certain conditions, this organism can
transform sugar via glucose-6-phosphate, fructose-6-phosphate
and fructose diphosphate.
In his communication to the Third International Congress
of Biochemistry in Brussels, F. Dickens^^^ gave the following
scheme for the interaction of the glycolytic and oxidative
mechanisms in metabolism (Fig. 42).
This diagram shoAvs where the Krebs cycle is incorporated
in the glycolytic mechanism and also the connection between
this mechanism and the direct oxidative degradation of
glucose. This scheme was worked out for the most part with
the animal cell, but Dickens considers that it is also valid
for yeast. Furthermore, the fact that the appropriate sugars
and enzymes are also found in higher plants (Calvin) suggests
that the mechanism also operates in these organisms.
Thus, although the first system of reactions taking part
in respiration varies considerably among the more primitive
470
FURTHER EVOLUTION
organisms, in higher organisms it has become standardised
to some extent."* There is less reason to suppose that the
same is true of the second system, which is devoted to the
oxidation to water of the hydrogen which is obtained during
GLYCOLYTIC
Pructose-6 -phosphate
(ATP)
Fructose- 1, b-diphosphate
Dihydroxyacetone ■ phosphate
+
Clyceraldehyde -3 - phosphote
OXIDATIVE
Glucose - b-phosphote
(TPN)
6-Phosphoqluconate
A
(TPN)
f
Pentose -5-phosphate + CO
{s mo/es)
(ThPP)
^ Sedoheptulose-?- phosphate
^ GlycerQlclehyde-3-phosphaf e
(DPN)-
Y blocked by I Ac ^
^ or F" /
Phosphopyruvote
Acetate-f CO? or Lactate
yio Krebs
Cycle
CO2
Fig. 42. Glycolytic and oxidative pathways for the
breakdown of glucose (after Dickens).
dehydrogenation, by means of atmospheric oxygen with the
formation of high-energy compounds at the expense of the
energy liberated by this reaction.
As is well known, the combination of gaseous oxygen and
hydrogen has such a high energy of activation that, at ordin-
ary temperatures, it hardly occurs at all. Organisms overcome
this energy barrier, breaking it down into a number of steps
so that the hydrogen is transferred successively through a
system of mediators with the help of a series of specific
RESPIRATION 471
enzymes. As in the case of glycolytic degradation this allows
the organism, not only to surmount the energy barrier, but
also to obtain the energy in separate, easily-used portions
rather than all at once, in an explosive form. At one end
of this chain stand phosphopyridine nucleotides and the corre-
sponding enzymes, dehydrogenases, which transfer hydrogen
from the system which we have referred to as the first, to the
second or oxidative system. At the other end of the chain
are the specific respiratory enzymes, oxidases and peroxidases,
the role of which, according to A. N. Bach,^^^ is the activation
of molecular oxygen and peroxides. They complete the
process of oxidation to water of the hydrogen which has been
brought into the system, and are therefore sometimes called
the ' terminal ' or ' finishing ' enzymes."® There is a consider-
able diversity in different organisms as regards the inter-
mediate links in the oxidative chain, but flavoproteins occupy
a prominent position, sometimes transferring hydrogen from
pyridine nucleotides to the oxidative mechanisms, and some-
times completing its oxidation by the oxygen of the air with
the formation of hydrogen peroxide. This is then broken
down by catalase or used for oxidising reactions by means of
peroxidases.
Recently H. Mahler"'' has shown that there are to be found
among living things a large number of flavoproteins having,
in their prosthetic groups, such metals as iron, molybdenum
and copper.
Mahler gives the following scheme for the part played by
flavoprotein enzymes in the transfer of the hydrogen liberated
in the first system to the oxygen of the air (Fig. 43). Under
the letter A we have the case in which the substance giving
up hydrogen to the flavine enzyme is reduced pyridine
nucleotide which has obtained hydrogen from the substrate
(from a reaction in the first system). The hydrogen is trans-
ferred by the flavine enzyme, either to a component of the
cytochrome system, or to some other oxidase mechanism, but
not directly to molecular oxygen. In the case designated by
the letter B the flavine enzymes taking part obtain hydrogen
directly from the substrate and transfer it to the cytochrome
system. Finally, the letter C refers to the case in which the
472 FURTHER EVOLUTION
flavoproteins act as true oxidases, i.e. they transfer the hydro-
gen which they receive directly to molecular oxygen.
("other Qccepror)
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Substrate »► FLAVOPROTEIN — »-cytochromes->02
FLAVOPROTEIN
Fig. 43. Role of the flavoproteins in
electron transport (after Mahler).
A. DPNH-oxidase ; DPNH-cytochrome reductase ;
TPNH-cytochrome reductase ; xanthine oxidase ;
nitrate, nitrite, hydroxylamine reductases ; dia-
phorase ; old, new yellow enzymes ; quinone
reductases. B. Lactic oxidase ; aldehyde oxidase ;
xanthine oxidase ; butyryl-CoA dehydrogenase ;
hydrogenase ; succinic dehydrogenase ; sulphite
oxidase. C. Amino-acid oxidases ; glucose oxidase ;
amine oxidases (?).
During the transfer of hydrogen from one link of the
respiratory chain to another high-energy bonds are formed.
According to F. Lipmann^^^ this is brought about by phos-
phorylation which proceeds in accordance with the following
scheme :
XH2 + Y->X + YH2
YH2 -I- H3P04-^YH2 — H2PO3
YH2 — H0PO3 4- Z^Y — H2PO3 + ZH2
Y — H0PO3 -f ADP->Y -t- ATP
where XH2 and z are successive members of the chain of
respiratory reactions and y is a third substance which acts
as an intermediary in the transfer of hydrogen from xHj to
z (xHo -f z-^x + ZH2). As we can see, this leads to the forma-
tion of one high-energy bond by the formation of atp from
ADP.
On the basis of his work with isolated mitochondria E.
Slater^^' puts forward a somewhat different scheme of oxida-
tive phosphorylation
XH2 + Z + Y^=^X f^ Y + ZH2
X v*Y + H3PO4 + ADP^^^X + Y + ATP
RESPIRATION
473
The main difference between this system and that of
Lipmann is that the high-energy bond is formed before the
inchision of the phosphate. This considerably enlarges our
ideas concerning the mobilisation of energy in the respiratory
process.
succinate
S.D.
aKg
p-OH
(DPT)
(CoA)
cyt. 6
(dehydrogenase)
(factor)
L.A.
I
DPN ^
I
\ (factor)
^ cyt. c
i
cyt. a
cyt. 03
\
Scheme A
(aKg'= a-ketoglutarate ; CoA = coenzyme A ; DPN =diphos-
phopyridine nucleotide; fp= flavoprotein ; cyt. =cytochrome ;
S. D. = succinic dehydrogenase ; L. A. = a-Hpoic acid ; P-OH
= p-hydroxybutyrate ; DPT = diphosphothiamiue)
Fig. 44. Diagram of the oxidative transformation of
respiratory substrates (after Slater).
Slater has worked out the above scheme (Fig. 44) of the
links of the chain of oxidation of a-oxoglutarate, succinate
and /3-hydroxybutyrate in which he remarks on the possible
ways in which phosphorylation may take part. According
to this scheme phosphorylation takes place at the following
stages of the process: between reduced diphosphopyridine
nucleotide (dpnh) and cytochrome c (here there may be two
stages at which phosphorylation occurs) ; between succinate
and cytochrome c ; and between cytochrome c and oxygen.
The great variety of the sequences of reactions in the
oxidative chain in different members of the animal and
vegetable kingdoms itself indicates the relatively recent origin
of the system under discussion, suggesting that evolution
474 FURTHER EVOLUTION
followed parallel paths in different organisms even at that
stage of the development of the living world when there first
occurred a clear-cut differentiation into its main divisions.
One may arrive at a similar conclusion from a study of the
numerous enzymes which take part in the chain of oxidative
transformations in different organisms. This specially con-
cerns the ' terminal ' group of catalysts which directly activate
molecular oxygen. In organisms which are far removed from
one another systematically this task is often accomplished by
widely different catalytic mechanisms. The earliest of these
would seem to be the cytochrome complex.^"" This, clearly,
owes its origin to the iron-porphyrin compounds of the
primaeval living things. Thus, as we have seen, cytochromes
are to be found in rather primitive anaerobic organisms.
With the appearance of molecular oxygen in the atmo-
sphere the most diverse representatives of the living world
could easily make use of the cytochromes present in them
as oxidase mechanisms, adapting them to the activation of
oxygen in the process of respiration.
As a result of this the cytochromes and the corresponding
enzymes, the cytochrome oxidases, seem to be very widely
distributed respiratory mechanisms ; we find them in a wide
variety of systematic groups of organisms, but their import-
ance is especially great in the respiratory processes of a
number of micro-organisms as well as in animal cells. In
higher plants the most important part in this connection
falls to the phenol oxidase system in which the enzymes are
copper-proteins,^" and the transporters of hydrogen are the
* respiratory chromogens ' of Palladin, especially chlorogenic
acid.^°^ These mechanisms are highly specific to plants and
are completely absent from members of the animal kingdom.
It is evident that in the process of phylogenesis they were
elaborated after the separation of organisms into the animal
and vegetable kingdoms.
In the ontogenesis of a number of plants we may also
observe that the cytochrome oxidase mechanism only plays
a leading part during the embryonic stage of development
when the plant is still leading a heterotrophic life.^"^ How-
ever, with the emergence of autotrophy in the plant we can
RESPIRATION 475
no longer find cytochrome oxidase in it and its work is
carried out, for the most part, by phenol oxidases.^"*
In the respiration of plants peroxidase, which activates the
oxygen of hydrogen peroxide, is also very important, though
in the animal cell it plays a comparatively small part.
Apart from cytochrome oxidase, phenol oxidase, per-
oxidase and the flavine enzymes, the final stages of oxidation
by the oxygen of the air may be carried out by a number
of other catalysts such as ascorbic acid oxidase, lipoxidase
and many other mechanisms. In different living things, and
at different stages in their life cycles, the parts played by each
of these mechanisms may vary within ver^' wide limits. All
this indicates the relatively recent phylogenetic origin of the
process of respiration, that it was elaborated considerably
later than the anaerobic habit of metabolism.
We have intentionally limited ourselves to a survey of the
evolution of only a few aspects of metabolism, mainly associ-
ated with the transformation of carbon, and have only
touched slightly on the problems of nitrogen metabolism ;
but even the little which has been said about that subject
in this chapter is enough to allow certain conclusions to be
drawn as to the order of development of the organisation of
matter.
The simplest forms of this organisation could only exist
under conditions where there was a continual accession from
the surrounding medium of diverse organic substances which
could serve as material for the construction of the components
of protoplasm and as sources of the energy needed for bio-
synthesis. The only method for the mobilisation of this energy
seems to have been the anaerobic breakdown of exogenous
organic substances.
The progressive evolution of the earliest organisms seems
to have been directed towards gradually making them more
and more independent of these conditions. Natural selection
led to the consolidation and further evolution of those organ-
isms in which the essential chemical reactions had become
co-ordinated into integrated systems of chains and cycles
which brought about the synthesis of complicated and specific
components of protoplasm from comparatively simple organic
molecules and their still simpler fragments. In addition the
476 FURTHER EVOLUTION
organisms acquired the ability to use a greater variety of
sources of energy than previously. This laid the basis for the
origin of autotrophy, the culminating development of which
was the photosynthesis developed by green plants, which
involved in the process of life that inexhaustible source of
energy, sunlight.
Photosynthesis led to the creation of an abundance of
organic substances and of an oxygen-containing atmosphere
on the Earth. These formed the basis for the origin of the
world of animals with their extremely intensive respiratory
metabolism and their rapid, progiessive development of
organic forms which, in the long run, led to the appearance
on our planet of a thinking being, man.
The contemporary process of the evolution of living things
is, in principle, nothing but a series of further links in that
unending chain of transformations of matter which began
in the earliest stage of the existence of the Earth.
BIBLIOGRAPHY TO CHAPTER IX
1. G. Ehrensvard, L. Reio and E. Saluste. Acta chem. scand.,
3> 645 (1949)-
J. Baddiley, G. Ehrensvard, E. Klein^ L. Reio and E.
Saluste. /. hiol. Chem., 18^, ']']'] (1950).
G. Ehrensvard. Svensk kem. Tidskr., 66, 249 (1954) ; Ann.
Rev. Biochem., 24, 275 (1955).
2. (V. 200).
G. R. Greenberg. Fed. Proc, 8, 202 (1949) ; P^ 179 (1950)-
(V. 203).
3. (V. 192).
4. N. H. Horowitz. Proc. nat. Acad. Sci., Wash., ^i, 153
(1945)-
5. C. B. van Niel. Physiol. Rev., 2^, 338 (1943).
6. (VIII. 64).
7. R. P. Hall. Quart. Rev. Biol., 14, 1 (1939).
8. A. LwoFF (ed.). Biochemistry and physiology of Protozoa.
New York, 1951.
9. A. LwoFF. L'evolution physiologique. £tude des pertes de
fonctions chez les microorganismes. Actualites sci.
ind., no. 970 (1944) ; Recherches biochimiques sur la
nutrition des protozoaires. Monographic d I'Institut
Pasteur. Paris, 1932.
BIBLIOGRAPHY 477
10. K. R. BuTLiN and J. R. Postgate in Autotrophic micro-
orgayiisms (ed. B. A. Fry and J. L. Peel), p. 271. Cam-
bridge, 1954.
1 1. V. PoLYANSKii. Priroda, 194'], no. 2, p. 20.
12. (IV. 35).
13. H. Dusi. Ann. Inst. Pasteur, ^o, 550, 840 (1933) ; 64, 340
(1940); yo, 311 (1944); Arch. Protistenk., 8g, 94
(1937) ; C.R. Soc. Biol., Paris, loy, 1232 (1931).
14. K. Ondratschek. Arch. Mikrobiol., 11, 89, 219 (1940).
15. E. G. Pringsheim. Pure cultures of algae, their preparation
and maintenance. Cambridge, 1946.
16. V. BuKiN. Personal communication.
17. P. A. Genkel' [Henckel]. Byull. Moskov. Ohshchestva
Ispytatelei Prirody. Otdel bioL, ^y, 13 (1938).
18. S. V. GoRYUNOVA. Mikrobiologiya, 24, s'ji (ig^p,).
19. W. H. ScHOPFER. Plants and vitamins (trans. N. L. Noecker).
Waltham, Mass., 1943.
20. C. Ternetz. Jb. loiss. Bot., ^i, 435 (1912).
21.0. Richter. Ber. dtsch. bot. Ges., 21, 493 (1903).
22. A. Artari. K voprosu o vliyanii sredy na formu i razvitie
vodoroslei. Moscow (Tip. M. Borisenko), 1903.
23. A. Pascher. Ber. dtsch. bot. Ges., ^^, 427 (1915).
24. R. Harder. Z. Bot., p, 145 (1917).
25. B. M. B. Roach. Ann. Bot., 41, 509 (1927).
26. C. B. Skinner and C. G. Gardner. /. Bad., ig, 161 (1930).
27. S. V. GoRYUNOVA. Khimicheskii sostav i prizhiznennye
vydeleniya sinezelenykh vodoroslei. Moscow and
Leningrad (Izd. AN SSSR), 1950.
28. B. Rubin. Fiziologiya rastenii. Moscow (Izd. ' Sovyetskaya
Nauka '), 1954-6.
29. J. B. Sumner and G. F. Somers. (VIII. 25).
30. S. WiNOGRADSKY [VlNOGRADSKIl]. Zbl. Bakt. Abt. 2, ^J , 1
(1922).
31. J. Meiklejohn in Autotrophic micro-organisms (ed. B. A.
Fry and J. L. Peel), p. 68. Cambridge, 1954.
32. A. Lebedev. Issledovanie khemosinteza u Bacillus hydro-
genes. Odessa (Tip. Shtaba Okruga), 1910.
33. W. Ruhland. ]b. iviss. Bot., 6^, 321 (1924).
34. K. Trautwein. Zbl. Bakt. Abt. 2, ^^, 513 (1921).
35. R. L. Starkey. /. gen. physioL, iS, 325 (1935) ; Soil Sci.,
39, 197 (1935)-
36. P. A. RoELOFSEN. On photosynthesis of the Thiorhodaceae.
Dissertation, Univ. Utrecht, 1935.
478 FURTHER EVOLUTION
37. M. S. Cataldi. Rev. Inst. bad. Dep. nac. Hig., B. Aires,
9> 393 (1940).
38. H. MoLiscH. Die Eisenbakterien. Jena, 1910.
39. R. LiESKE. Zbl. Bakt. Aht. 2, 4p, 41$ (iQiQ).
40. M. S. Cataldi. Estudio fisiologico y sistematica de algunas
Chlamydobacteriales. Doctoral thesis, Univ. Buenos
Aires, 1939. See Rev. Inst. bact. Dep. nac. Hig., B.
Aires, 9, 1 (1939).
41. V. O. Kalinenko. Mikrobiologiya, 10,401 (1941).
42. C. B. VAN NiEL. Ayin. Rev. Microbiol., 8, 105 (1954).
43. H. BoMEKE. Arch. MikrobioL, 10, 385 (1939).
44. K. G. VoGLER. /. gen. Physiol., 25, 617 (1942).
45. K. G. VoGLER and W. W. Umbreit. /. gen. Physiol, 26, 157
(i94«)-
46. K. Baalsrud and K. S. Baalsrud in Phosphorus metabol-
ism: a symposium on the role of phosphorus in the
metabolism of plants and animals (ed. W. D. McElroy
and B. Glass). Vol. 2, p. 544. Baltimore, Md., 1953.
47. R. W. Newburgh. /. Bact., 68, 93 (1954).
48. W. W. Umbreit. /. Bact., 6'], 387 (1954).
49. G. A. LePage and W. W. Umbreit. /. biol. Chem., i^y,
263 (1943)-
50. H. A. Barker and A. Kornberg. /. Bact., 68, 655 (1954).
51. Yu. I. SoROKiN. Doklady Akad. Nauk S.S.S.R., p^, 661
(1954)-
52. Yu. I. SoROKiN. Trudy Inst. MikrobioL, Akad. Nauk
S.S.S.R.,^,21 (1954)-
53. H. Lees in Autotrophic micro-organisms (ed. B. A. Fry and
J. L. Peel), p. 84. Cambridge, 1954.
54. E. L. RuBAN. Mikrobiologiya, 2^, 103 (1956).
55. (IX. 44).
56. E. J. Russell and H. B. Hutchinson. /. agric. Set., 5^ 111
(1909)-
57. V. O. Tauson. Priroda, 19^4, no. 6, p. 43.
58. V. O. Tauson. Energetika sinteticheskikh protsessov v
kletke. Communication to General Assembly of Acad-
emy of Sciences U.S.S.R., 1940; Osnovnye polozheniya
rastiteVnoi bioenergetiki. Moscow and Leningrad
(Izd. AN SSSR), 1950.
59. C. E. ZoBELL. Advanc. Enzymol., 10, 443 (1950).
60. V. O. Tauson and V. I. Aleshina. Mikrobiologiya, i, 229
(1932); 5.523(1934)-
61. W. O. Rosenfeld. /. Bad., ^4, 664 (1947).
BIBLIOGRAPHY 479
62. A. C. Thaysen. Congr. int. Microbiol., 3, 729 (1940).
63. H. F. Haas. Thesis, Kansas State College, 1942. Cf. /. Bact.,
48,219 (1944)-
F. H. Johnson, W. T. Goodale and J. Turkevich. /. cell.
comp. Physiol., ip, 163 (1942).
64. A, Lebedev. Izvestiya Donskogo Gosudarstvennogo Uni-
versiteta, /^ 25 (1921).
65. G. L. Seliber. Priroda, 1^42, no. 5-6, p. 85.
66. I. L. Rabotnova, M. V. Ulubekova and L. V. Magnitskaya.
Mikrobiologiya, 79,401 (1950).
67. V. E. PoNTOViCH. Izvest. Akad. Nauk S.S.S.R., Ser. Biol.
ip^i. No. 5, p. 120.
M. F. Utter and H. G. Wood. Advanc. Enzymol., 12, 41
(1950-
68. C. H. Werkman in Bacterial Physiology (ed. C. H. Werkman
and P. W. Wilson), p. 404. New York, 1951.
69. H. G. Wood and C. H. Werkman. Biochem. ]., ^2, 1262
(1938).
70. A. L. KuRSANOv. Izvest. Akad. Nauk S.S.S.R.j Ser. Biol.
ip^4. No. 1, p. 8.
71. F. LiPMANN. /. biol. Chem., 160, 173 (1945); Bact. Rev.,
n> 1 (1953)-
G. D. Novelli. Fed. Proc, 12, 675 (1953).
72. D. Nachmansohn and M. Berman. /. biol. Chem., 16^, 551
(1946).
73. W. Feldberg and T. Mann. /. Physiol., 104, 411 (1946).
74. F. Lynen, E. Reichert and L. Rueff. Liebigs Ann., ^J4,
1 (1951)-
75. K. Burton. Biochem. J., 59, 44 (1955).
76. H. Beinert, D. E. Green, P. Hele, H. Hift, R. W. von
KoRFF and C. V. Ramakrishnan. /. biol. Chem., 20^,
35 (1953)-
77. E. J. Simon and D. Shemin. /. Amer. chem. Soc, 75, 2520
(1953)-
78. B. K. Bachhawat, W. G. Robinson and M. J. Coon. /.
biol. Chem., 2ip, 539 (1956).
79. D. D. Woods and J. Lascelles in Autotrophic micro-
organisms (ed. B. A. Fry and J. L. Peel), p. 1. Cam-
bridge, 1954.
80. K. T. WiERiNGA. Leeuwenhoek Jied. Tijdschr., ^, 263 (1936) ;
6, 251 (1940).
8i. H. A. Barker, S. Ruben and J. V. Beck. Proc. nat. Acad.
Sci., Wash., 26, 477 (1940).
480 FURTHER EVOLUTION
82. E. Pfluger. Pfli'ig. Arch. ges. Physiol., 10, 251 (1875).
83. W. Pfeffer. Landw. ]h., y, 805 (1878).
84. V. Palladin and S. Kostychev. Trav. Soc. Nat. St. Petersb.,
38, 9 (1907).
85. S. Kostychev. Issledovaniya nad anaerobnym dykhaniem
rastenii. St. Petersburg (Tip. Shredera), 1907.
86. S. Kostychev. Fiziologiya rastenii. Part 1. Moscow and
Leningrad (Sel'khozgiz), 1933.
87. O. Meyerhof. Chemical dynamics of life phaenomena.
Philadelphia and London, 1924.
88. G. Embden and F. Kraus. Biochem.Z.,4^,\ (1912).
89. Ya. O. [J. K.] Parnas. Uspekhi sovremennoi Biol., 12, 393
(1940).
90. (VIL81).
91. A. J. Kluyver and W. J. Hoppenbrouwers. Arch. Mikro-
biol.,2,24r, (1931).
92. M. GiBBS and R. D. DeMoss. /. biol. Chem., zcy, 689
(1954)-
93. B. RosENFELD and E. Simon. /. biol. Chem., 186, 395 (1950).
94. V. Shaposhnikov. Tekhnicheskaya mikrobiologiya. Moscow
(Izd. ' Sovetskaya Nauka '), 1948.
J. B. van der Lek. Onderzoekingen over de Butylalkohol-
gisting. Delft, 1930. Quoted by K. V. Thiraann
(in. 1).
H. J. L. Donker. Quoted by K. V. Thimann (III. 1).
95. H. G. Wood, R. W. Brown and C. H. Werkman. Arch.
Biochem.,6, 243 (1945)-
96. H. A. Barker. Leeuwenhoek ned. Tijdschr., 12, 167 (1947)-
97. H. J. KoEPSELL, M. J. Johnson and J. S. Meek. /. biol.
Chem., 1^4, 535 (1944).
98. S. KoRKES^ A. DEL Campillo, I. C. GuNSALUs and S. Ochoa.
/. biol. Chem., ig^, 721 (1951).
99. I. C. GuNSALUs and M. Gibbs. /. biol. Chem., 1^4, 871
(1952).
loo. I. C. GuNSALUS, L. Struglia and D. J. O'Kane. /. biol.
Chem., 194, 859 (1952).
loi. L. J. Reed. Physiol. Rev., 55^ 544 (1953).
102. E. A. Delwiche and S. F. Carson. /. Bact., 6^, 318 (1953).
103. P. Chaix and C. Fromageot. Trav. Membres Soc. Chim.
biol., 24, 1125, 1128 (1942).
104. A. I. Virtanen. Acta chem. Fenn., B6, 14 (1931).
105. V. W. Cochrane. /. Bact., 69, 256 (1955).
106. E. Simon. Biochem. Z., 224, 253 (1930).
BIBLIOGRAPHY 481
107. N. D. Gary and R. C. Bard. /. Bad., 64, 501 (1952).
108. A. LwoFF, H. loNESco and A. Gutmann. C.R. Acad. Sci.,
Paris, 228, 342 (1949)-
109. H. G. Albaum, a. Schatz, S. H. Hutner and A. Hirshfeld,
Arch. Biochem., 2^, 210 (1950).
110. S. C. Harvey. /. hiol. Chem., lyp, 435 (1949).
111. R. W. McKee in (IX. 8), Vol. I, p. 251.
112. S. KosTYTscHEW [KosTYCHEv]. BcT. dtsch. bot. Ges., 2^, 44
(1907)-
H. Tamiya and Y. Miwa. Z. Bot., 21, 417 (1928).
113. T, Takahashi, K. Sakaguchi and T. Asai. Bull, agric.
chem. Soc. Japan, ^, 87 (1927).
114. T. Takahashi and T. Asai. Bull, agric. chem. Soc. Japan,
4, 15 (1928).
115. J. C. VV^iRTH and F. F. Nord. Science, g2, 15 (1940).
116. S. KosTYTSCHEW [KosTYCHEv]. Pflanzeuatmung. Berlin,
1924.
F. F. Blackman. Analytic studies in plant respiration
(assembled by J. Barker). Cambridge, 1954.
117. H. Gaffron. Biol. Zbl., ^p, 288 (1939).
H. MicHELS. Z. Bot., 55^ 241 (1940).
118. H. Gaffron and J. Rubin. /. gen. physioL, 26, 219 (1942).
119. M. Calvin, J. A. Bassham and A. A. Benson. Fed. Proc,
9> 524 (1950)-
120. E. W. Fager, J. L. Rosenberg and H. Gaffron, Fed. Proc,
9> 535 (1950)-
121. P. K. Stumpf in Phosphorus metabolism: a symposium on
the role of phosphorus in the metabolism of plants
and animals (ed. W. D. McElroy and B. Glass), Vol. 2,
p. 29. Baltimore, Md., 1952.
122. S. KosTYTSCHEW [KosTYCHEv]. Pflauzeuatmung. Berlin,
1924.
123. A. Putter. Z. allg. Physiol., 5, 566 (1905).
124. A. VON Szent-Gyorgyi in Perspectives in biochemistry (ed.
J. Needham and D. E. Green), p. 165. Cambridge,
1937-
125. O. Harnisch. Biol, gen., 18, 30 (1944).
126. G. F. Humphrey and L. Siggins. Austr. J. exp. Biol. med.
Sci., 2'], 353 (1949).
127. E. BuEDiNG. /. gen. Physiol., 55, 475 (1950).
128. W. P. Rogers and M. Lazarus. Parasitology, ^p, 302 (1949).
129. C. P. Read. Proc. Soc. exp. Biol., N.Y., 'j6, 861 (1951).
31
482 FURTHER EVOLUTION
30. G. F. Humphrey. Austr. J. exp. Biol. med. Sci., 28, 151
(1950)-
31. P. K. Stumpf in Chemical pathways of metabolism (ed.
D. M. Greenberg), Vol. 1, p. 67. New York, 1954.
32. J. P. Greenstein and A. Meister in The enzymes (ed. J. B.
Sumner and K. M)Tback), Vol. 2 (part 2), p. 1131.
New York, 1952.
33. E. S. Guzman Barron. Advanc. Enzym,ol., ^, 149 (1943).
34. H. E. HiMWiCH. Brain metabolism and cerebral disorders.
Baltimore, Md., 1951.
35. Z. D. PisAREVA and D. A. Chetverikov. Doklady Akad.
Nauk S.S.S.R., yS, 393 (1951).
36. N. Verkhbinskaya in Materialy po evolutsionnoi fiziologii
(ed. L. A. Orbeli). Vol. 1, p. 59. Moscow and Lenin-
grad (Izd. AN SSSR), 1956.
37. F. Weigert. Z. phys. Chem., 106, 313 (1923).
38. A. Terenin. Fotokhimiya krasitelei. Moscow and Lenin-
grad (Izd. AN SSSR), 1947.
39. M. Nentskii [Nencki]. Arch. Sci. bioL, St. Petersb., ^, 254
(1897)-
M. Nentskii and L. Markhlevskii [Marchlewski]. Ibid.,
9> 387 (1902).
40. R. Lemberg and J. W. Legge. Hematin compounds and
bile pigments. New York, 1949.
41. D. A. Webb. /. exp. Biol., 16, 499 (1939).
42. D. E. Green and L. H. Stickland. Biochem. J., 28, 898
(1934)-
43. (VL 65).
44. M. Stephenson and L. H. Stickland. Biochem. J., 2^, 205,
215 (1930-
45. S. B. Lee, J. B. Wilson and P. W. Wilson. /. biol. Chem.,
i44> 273 (1942)-
46. H. Gaffron and J. Rubin. /. gen. Physiol., 26, 219 (1942).
H. Gaffron. Biol. Rev., 19, 1 (1944).
47. E. A. BoicHENKO. Biokhimiya, i^, 21^ {\^4^).
48. M. IsHiMOTO, J. KoYAMA and Y. Nagai. /. Biochem., Japan,
4^> 763 (1954)-
M. IsHiMOTo and J. Koyama. Bull. chem. Soc, Japan, 28,
231 (1955)-
BIBLIOGRAPHY 483
149. A. A. Krasnovskii. Doklady Akad. Nauk S.S.S.R., 60, 421
(1948); 705,283(1955).
A. A. Krasnovskii and K. K. Voinovskaya. Biofizika, i,
120 (1956).
150. A. A. Krasnovskii. Zhur. fiz. Khim., ^o, 968 (1956).
151. A. A. Krasnovskii in Voprosy khimicheskoi kinetiki, kata-
liza i reaktsionnoi sposobnosti (ed. V. N. Kondrat'ev
and N. M. Emanuel), p. 92. Moscow (Izd. AN SSSR),
1955 ; Izvest. Akad. Nauk S.S.S.R., Ser. biol., 7955,
No. 2, p. 122.
152. T. W. Engelmann. Pflilg. Arch. ges. Physiol., ^o, 95 (1883).
153. H. Fischer and J. Hasenkamp. Liebigs Ann., ^ip, 4.2 (iQ^^).
154. F. M. MuLLER. Arch. Mikrobiol.,4, 131 (1933).
155- J- W. Foster. /. Bact., 4-], 355 (1944).
156. J. W. Foster in Bacterial physiology (ed. C. H. Werkman
and P. W. Wilson), p. 361. New York, 1951.
157. C. B. VAN NiEL. Arch. Mikrobiol., 5, 1 (1931).
158. C. B. VAN NiEL. Arch. Mikrobiol., y, 323 (1936).
159. C. B. VAN NiEL in Photosynthesis in plants (ed. J. Franck
and W. E. Loomis), p. 437. Ames, Iowa, 1949.
160. C. B. VAN NiEL. Amer. Scientist, ^y, 2,"] I (1949)-
161. H. Gaffron. Amer. J. Bot., 2y, 2*]^ (ig^o).
162. K. Bernhauer. Ergebn. Enzyt7iforsch., ^, i8Pf (iQ^^).
163. M. MiYOSHi. /. Coll. Sci. Tokyo, 10, 143 (1896).
B. L. Isachenko and A. G. Salimovskaya. Izvest. gos.
gidrolog. Inst., 21, 1 (1928).
164. A. G. Salimovskaya. Izvest. gos. gidrolog. Inst., ^6, 43
(1930-
B. L. Isachenko. Mikrobiologiya, 6, 964 (1937).
C. L. Corey. /. mar. Res., i, 291 (1938).
165. N. Cholodny [Kholodnyi]. Die Eisenbakterien : Beitrdge
zu einer Monographic. In series Pflanzenforschung
(ed. R. Kolkwitz), Heft 4. Jena, 1926.
R. L. Starkly. Science, 102, 532 (1945).
166. C. E. ZoBELL. Bull. Amer. Ass. Petrol. GeoL, ^i, 1709 (1947).
167. S. I. KuzNETSOV. Mikrobiologiya, ^, 486 (1934) ; 16, 429
(1947); ^7.307(1948).
168. O. Jensen. Zbl. Bakt. Abt. 2, 22, 305 (1909).
169. C. B. van Niel. Physiol. Rev., 2^, 338 (1943).
B. A. Fry and J. L. Peel (ed). Autotrophic micro-organisms.
Cambridge, 1954.
170. D.J. O'Kane. /. 5ac^., ^7,441 (1941).
171. Yu. Sorokin. Dissertation. Moscow, 1954.
484 FURTHER EVOLUTION
172. R. Hill and C. P. Whittingham. Photosynthesis. London
1955-
173. E. I. Rabinowitch. Photosynthesis and related processes
Vols. 1 and 2 (Parts 1 and 2). New York, 1944, 1951
1955-
174. E. I. Rabinowitch. Sci. Amer., i8g, November, p. 80 (1953)
175. M. Calvin. Conferences et Rapports, ^-eme Congres inter-
national de Biochimie, Bruxelles, 1-6 Aout 19^5, p
211. Liege, 1956.
175a. A. A. Krasnovskii and L. M. Kosobutskaya. Doklady
Akad. Nauk S.S.S.R., 10^, 440 (1955).
L. M. Vorob'eva and A. A. Krasnovskii. Biokhimiya, 21,
126 (1956).
L. Bell. Doklady Akad. Nauk S.S.S.R.j icj, 329 (1956).
B. L. Strehler and V. H. Linch. Science, 12^, 462 (1956).
176. A. Bach. C.R. Acad. Sci., Paris, 116, 1145 (1893) ; Arch. Sci.
phys. nat., i8p8. Vol. 5, pp. 287, 401 ; [A. N. Bakh].
Sbornik isbrannykh trudov.. No. 1. Moscow (ONTI),
1937.
177. A. P. Vinogradov and R. V. Teis. C.R. Acad. Sci., U.S.S.R.,
55.490(1941); 5^.59(1947)-
178. S. OcHOA in Currents in biochemical research (ed. D. E.
Green), p. 165. New York, 1946.
179. A. A. Krasnovskii and G. P. Brin. Doklady Akad. Nauk
S.S.S.R.,67,S25 (1949)-
A. A. Krasnovskii and K. K. Voinovskaya. Doklady Akad.
Nauk S.S.S.R.,8'j, 109 (1952).
180. A. A. Krasnovskii. Uspekhi biologicheskoi Khimii, i, 473
(1950)-
181. W. ViSHNiAC and S. Ochoa in Phosphorus metabolism: a
symposium on the role of phosphorus in the metabol-
ism of plants and animals (ed. W. D. McElroy and
B. Glass), Vol. 2, p. 467. Baltimore, Md., 1952.
182. (Vin.39).
183. R. Hill. Conferences et Rapports, ^-eme Congres inter-
national de Biochimie, Bruxelles, j-6 Aout 19^^, p.
225. Liege, 1956.
184. D. I. Arnon, M. B. Allen, F. R. Whatley^ J. B. Capindale
and L. L. Rosenberg. Ibid., p. 227.
D. I. Arnon. Science, 122, 9 (1955).
185. Y. Oda. Kagaku, 2^, 455. {cf. Chem. Abstr., ^o, 14825
(1956)).
BIBLIOGRAPHY 485
186. H. A. Krebs. 2-eme Congr. intern, biochim. Symposium
sur le cycle tricarboxylique, p. 42. Paris, 1952.
S. OcHOA. Ibid., p. 73.
187. (VIII. 49).
188. (VIII. 50).
189. W. A. Wood. Conferences et Rapports, ^-eme Congres inter-
national de Biochimie, Bruxelles, 1-6 Aoiit 19^^, p.
179. Liege, 1956.
190. V. A. Engel'gardt [Engelhardt] and A. P. Barkhash.
Biokhimiya, ^, 500 (1938).
191. H. R. V. Arnstein and R. Bentley. Biochem. ]., ^4, 493
(1953)-
192. P. KoLESNiKov in Sbortiik nauchnykh rabot komsomol'tsev-
biologov. (ed. I. I. Shmal'gauzen), p. 75. Moscow and
Leningrad (Izd. AN SSSR), 1940.
193. F. Dickens. Conferences et Rapports, yeme Congres inter-
national de Biochimie, Bruxelles, j-6 Aout 19^^, p.
170. Liege, 1956.
194. H. A. Krebs in Chemical pathways of metabolism (ed.
D. M. Greenberg). VoL 1, p. 109. New York, 1954.
195. A. N. Bakh [Bach]. /. Russ. phys.-chem. Soc. (Chem. Sec-
tion), ./^^ div. 2, 1 (1912).
196. D. M. MiKHLiN. Uspekhi sovremennoi Biol., 55, 1 (1952) ;
Biologischeskoe okislenie. Moscow (Izd. AN SSSR),
1956-
197. H. R. Mahler. Conferences et Rapports, yeme Congres
international de Biochimie, Bruxelles, 1-6 Aout ip^$,
p. 252. Liege, 1956.
198. F. LiPMANN. Advanc. Enzymol., 6, 2^1 (1946).
199. E. C. Slater. Conferences et Rapports, yeme Congres
internatio7ial de Biochimie, Bruxelles, 1-6 Aout 19^^,
p. 264. Liege, 1956.
200. D. Keilin. Ergebn. Enzymforsch., 2, 239 (1933).
201. F. KuBOWiTZ. Biochem. Z., 292, 221 (1937) ; '299, 32 (1938).
202. A. Oparin. Biochem. Z., 182, 155 (1927).
203. D. M. Mikhlin and K. V. Pshenova. Biokhimiya, 16, 5
(1951)-
204. A. I. Oparin and T. A. Shubert. Biokhimiya chainogo
Proizvodstva. Sbornik no. 6 (ed. V. V. Potemkin, M. I.
Leont'eva, A. V. Blagoveshchenskii and A. I. Oparin),
p. 82 (1950). Cf. Chem. Abstr., 46, 2631 (1952).
CONCLUSION
IN coNCLUSiOxN I sliould like to spend a little time on a
question which is very often put to me concerning the
origin of life, the question as to the possibility of life
originating now, in our own time. In the scientific literature,
and especially in the literature of popular science, there is
rather a lot of confusion on this subject. This seems to be
due to the fact that the problem itself is commonly construed
in the most diverse ways. It would therefore be worth while
to consider all its possible variants.
Does life arise now, at the present time? Yes, it undoubtedly
does. Life, as one of the forms of the motion of matter, must
arise every time suitable conditions for it occur at any place
in the Universe. Contemporary astronomical evidence shows
convincingly that even now, in various parts of our galaxy,
there are being formed new stars and new planetary systems.
No doubt on many of these planets the process of develop-
ment of matter is following a course analogous to that which it
followed on the Earth, and thus the development of life must
be proceeding on them.
However, the people who put the question are usually
concerned with a more limited aspect of the matter, being
interested in whether life is coming into being now on the
Earth, and not in the Universe in general. This is another
aspect of our problem, but even when the question is under-
stood in this way we must still give a positive answer. Every
day we observe the birth of living things. Living things
arise now, but only through the agency of other living things.
The origin of living things by these means can only take
place at a very high stage in the development of matter.
With the origin of life, i.e. metabolism, there arose synthetic
paths and new and extremely effective methods of building
up living material. Obviously this could not take place
before the origin of life and therefore the development of
matter from the lifeless to the living stage took place at
that time by very slow and involved means as we have shown
487
488 FURTHER EVOLUTION
above. At first organic materials developed over the course
of many hundreds of millions of years. Then they were trans-
formed into polymers of high molecular weight which formed
individual open systems, and only as a result of the directed
evolution of these systems did there arise the first, primitive
organisms, the simplest forms of life.
However, when this happened the origin of living from
lifeless material began to take place on a gigantic scale with
extraordinary thoroughness, as we can see every day and
everywhere at the present time.
The people who put the question are not, however, usually
interested in the origin of living material through the agency
of living things (this seems to them very trivial), but in
whether living material can now arise on our Earth primarily,
directly in a lifeless natural medium. This is yet a third
aspect of our question.
Many people give a purely theoretical answer to this, being
convinced that when once any form of the motion of matter
has arisen, then it must still go on arising now. This assump-
tion, however, is only valid for the Universe as a whole and
not for some particular limited system such as the Earth.
In this case such a presentation of the problem can lead to
a completely unwarrantable inference.
To clarify this I shall give the following simple example.
The origin of man was undoubtedly one of the most import-
ant stages in the development of matter. This stage is wholly
comparable with the origin of life. If the origin of life
involved the appearance of a new, biological form of the
motion of matter, so man is the culmination of this biological
development and his origin involved the transition to a still
higher, social form of the motion of matter. We do not doubt
that man arose on the Earth during the process of the develop-
ment of life but there can hardly be anyone who would main-
tain that he arises nowadays on our planet without being
born from another like himself, but in some other way.
Let us imagine some sterile tank of water, free from living
things, with various organic substances dissolved in the water.
If it were left to itself, the processes of transformation of sub-
stances which we described above would come about slowly
in it. Finally, during many millions of years, this would lead
CONCLUSION 489
to the origin of life. However, if we were to introduce into
our tank ready-made organisms, e.g. bacteria, the course of
events would be quite different ; in that case the more
highly developed form of the motion of matter would come
to the fore and take the lead. At once the transformation of
lifeless to living material would cease to follow the old slow
paths and would proceed in the new way, based on metabol-
ism, converting the organic substances in the solution into
the ingredients of living protoplasm with colossal rapidity.
The origin of life from lifeless material simply could not
occur under these conditions. It would, in fact, be completely
ruled out, as Darwin pointed out long ago and as, indeed, we
can see everywhere in nature.
Of course, in some out of the way parts of our planet where,
for some reason, there are no organisms, but where the
circumstances are suitable, it might be that the process of
the primary formation of life is, even now, taking place.
However, if we are to accept this possibility as a fact, the
process must first actually be found taking place under
natural conditions, but nobody has yet succeeded in doing
this. A far more rational approach to a solution of the
problem of the origin of life would seem to be the study of
the ways in which lifeless material is transformed into
living material as manifested in metabolism. A detailed
study of the processes of metabolism is the very thing which
can lead towards a solution of the problem of reproducing
it artificially. By studying this high form of the organisation
of matter which is characteristic of living bodies we shall be
able to proceed far more efficiently than nature and shall
be able to synthesise life at a far greater rate. One may rest
assured that this is a matter for the not so distant future.
INDEX
Abiogenesis of organic compounds
nitrogenous, 170, 172, 178-84, 188,
192, 196, 202-5, 207, 213-6
phosphorus-containing, 205-9
sulphur-containing, 171, 184, 188,
196, 214
oxygen-containing, 153-4, 162-6,
170-2, 174, 177-82, 189, 198-
200
Adsorption
on inorganic catalysts, 188, 195,
214, 304, 339
in coacervates, 311, 314, 353, 371,
385
Albertus Magnus, 10
Amino acids (cf. Polypeptides, Pro-
teins)
abiogenesis, 96, 100, 108, 179-81,
203, 211, 214, 216
biosynthesis of, 401, 413
common, 237-9
uncommon, 240
Amino acid radicals, 238-42, 250,
252
arrangement in peptides, 236,
241-5
arrangement in proteins, 234,
236-60, 267-8, 370
Ammonia
cosmic distribution, 119-20, 137-40
on primitive Earth, 97, 141-3,
172, 178-83, 201
Anabiosis, 60-1, 67, 187, 312
Anaerobiosis
anaerobic metabolism, 413, 416-
29
primitiveness, 400, 402
transition to aerobiosis, 430-8
Antibiotics, 108, 190, 240, 243,
251, 282, 361, 403
Aquinas, Thomas, 10
Aristotle, 5-10
Arrhenius, S., 57-9, 63
Astronauts, 68
Asymmetry, 48-9, 100, 189-96
asymmetric synthesis, 183, 192-6,
216, 388-90
Atmosphere of Earth
enrichment with oxygen, 143,
156-9, 446-50, 463
primaeval (cf. Evolution, chemi-
cal), 81, 94-5, 141-3, 155-6, 158-
62
radiations, absorption by, 63, 161-3
Atmospheres
of planets, 95, 118-20, 125, 142
of stars, 1 15-7, 125
Augustine of Hippo, St., 9-10, 44
Autocatalysis (cf. Self reproduc-
tion)
Bacon, Francis, 16
Basil the Great, St., 8-9, 11
Borodin, I., 32, 35
British Association, 73, 92
Bruno, Giordano, 15, 51
Buffon, G. L., 21
Carbides, 123, 125-9, 140-2, 159-61,
167-8
Carbohydrates {cf. Glycolytic sys-
tems)
abiogenesis of, 189, 198-201
laboratory synthesis, 108, 162-5
Carbon dioxide, fixation of, 110,
407, 411-2, 414-5, 417-8
Catalysts (cf. Enzymes)
analogous to enzymes, 245-6, 371-3
in stationary open systems, 331,
333-5. 379
simple, 170-4, 188, 195-6, 199,
211, 214-5
491
492
INDEX
Chain reactions, catalytic (cf. Fer-
mentation, Tricarboxylic cycle),
336, 338
prebiological evolution of, 359-
85
Chain reactions, ionic, 335-9
Chemoautotrophs
metabolism, 110, 263, 408-12, 450-5
not primitive, 113, 408-10
Chlorophyll, 360-1, 408, 442-3
Christianity, 8-13
Coacervates, 303-21, 340-1, 351-9,
363. 371-3. 376, 385. 390
Coenzyme A, 201, 208, 265, 334,
361, 415-7, 428-9, 464
Comets, 124-5
Core of the Earth, 121, 125, 128,
140, 142, 168
Cosmic dust, 52-3, 56-9, 117-8, 124-5,
133-7
Cytoplasm, 86, 271-2, 312-4, 379-80
Epicurus, 3, 4
Evolution, biological, 114, 239-40,
260-1, 285, 350-1, 363, 373, 388,
397-476
Evolution, chemical
in the atmospliere, 153, 162-4,
175-85. 335-6
in the hydrosphere, 97-8, 153,
166-7, 185-8, 195-217, 259-61
in the lithosphere, 165-75
Evolution, prebiological, 24, 74-5,
78-9, 92-102, 260-1, 287-90,
301-2, 319-20, 338-41, 347-93
Fermentation, 263, 364, 398
alcoholic, 337, 375-6, 383, 386,
420-8
butyiic, 417, 428
extracellular, 375-7, 383
lactic, 420, 428-9, 434
other forms, 428
Darwin, Charles, 32-3, 75, 79, 289
Democritus, 3-4
Descartes, 16
Dimitrii Rostovskii, 11
Dusch, T., 26, 28-9
Electric discharges, 79-80, 97, 163-4,
166, 175-80, 183-5, 197. 203,
205, 333, 335
Empedocles, 3, 260-1
Energy of activation, 175, 365-8,
387, 421, 470
Energy metabolism (cf. Glycolytic
systems), 381-3, 386-8, 391-2, 399-
404, 409-13, 419-37
Engels, F., 33-4, 46, 92, 230-1, 348-9
Enzymes
abiogenesis, 93-7, 217, 261-2
active centres of, 247, 250-3, 372
co-ordination, 364-6, 374-85
enzyme-substrate complex, 237,
250-1, 336, 368-70
evolution, 261, 369-73, 401-2
localisation of, 380-1
prosthetic groups, 245-7, 366. 369,
372, 403, 439-43, 454, 471
protein nature, 233-5, 245-52,
255. 259, 366-7
specificity, 367-83
in stationary systems, 327-9, 331
Gay-Lussac, J. L., 25, 30
Genes, 95-6, 99, 339
Germinal plasm, 85
Glycolytic systems
mechanisms, 263-4, 386-7, 420-31
in various organisms, 114, 263,
414, 431-6
oxidative, 467-70
universality, 388, 426
Goose trees, 12-3
Haeckel, E., 34, 77-8, 82
Haemoglobin, 439-40
Harvey, 16
Hegel, 24
van Helmont, 15-6, 35, 44
Heterotrophic metabolism
in various organisms, 406-11, 414,
444-5
primitiveness, 113-5, 399"4oo, 402,
418
High-energy compounds
abiogenic synthesis of, 207-9
localisation, 271-2, 381
in metabolism, 100, 114, 264-6,
387, 391, 411, 416, 421-6, 457,
460-1
Homunculus, 12-5
Hormones, 233-5, 243-5, 252, 255,
259-60
INDEX
498
Huxley, T. H., 73-4
Hydrocarbons (cf. Polymerisation)
abiogenesis of, 67, 94-5, 109,
129-30, 159. 165-9
abiogenic transformation of, 142-3,
153, 161, 164-85, 205
in atmosphere, 166, 175-9, 185
cosmic distribution, 54-5, 116-
27, 137-41. 153
in hydrosphere, 167, 175, 186
in lithosphere, 167-9, 173-7
saturated, 118-20, 130, 137-9, i43'
170, 182
unsaturated, 67, 119-20, 143, 170-1,
182, 184, 202-3, 215
in volcanic gas, 160, 167, 175
Hydrocarbon-using organisms, 412-4
Hydrosphere (cf. Evolution, chemi-
cal, prebiological)
catalysts in, 371
coacervates in, 319-21, 340, 356
open systems in, 339-41, 356
primaeval, 97-8, 141, 153, 155-6,
206, 449
Hylozoism, 44-6
Idealism, 6, 23, 31-3, 43, 45-7, 73,
107, 347
Insulins, 235, 243-4, 252, 257
Isotopic composition of elements,
49-50, 111, 116, 122, 128, 143
Joblot, Louis, 20
Meteorites, 52-7, 120-5, 127, 140
Microsomes, 269, 271-2, 380-2
Mitochondria, 98, 266, 268-72, 380-1
Needham, J. T., 21-2, 25, 27, 36, 44
Nitrogen compounds, inorganic (cf.
Ammonia), 74, 84, 116, 138,
142, 178-82, 203
Nucleic acids
abiogenesis, 208-9, 211
biosynthesis, 208-10, 216, 271,
286-8, 391-2
in coacervates, 310
in protein synthesis, 265, 267-8,
272-90, 362
structure, 280-4
Nucleoproteins
abiogenesis, 217
self-reproduction, 232
viral, 275-9
Nucleosides
abiogenesis, 203-5
biosynthesis, 205
Nucleotides
abiogenesis, 189, 203, 205, 319
in nucleic acids, 275, 279-85
in peptide synthesis, 282-3
Nucleus, 86, 93, 271-2, 312, 314
Oken, L., 24, 75
Oxygen (cf. Atmosphere, Photo-
synthesis)
Ozone screen, 63-6, 163, 181, 438
Kant, I., 23-4, 132-3
Kircher, Athanasius, 44
Lamarck, 74-5
van Leeuwenhoek, 19
Leibnitz, 20, 44
Liebig, 46-7
Lipids
abiogenic formation, 189, 200-1
biosynthesis, 391, 413, 415
laboratory synthesis, 108
Lithosphere, 121, 141-2, 155-6, 159,
165-77, 184, 188
Materialism, 3, 16, 31-5, 44-7, 50,
73-4. 92. 339. 347-8
Panspermia, 43, 52-60, 64, 69, 77,
93- 112
Paracelsus, 14-6, 44
Pasteur, Louis, 28-31, 37, 45, 48,
50. 55. 375. 388
Pentoses
abiogenesis, 199
in alcoholic fermentation, 428
in nucleosides, 205, 208
Peptide formation, 208-16, 232,
259-60, 264-7, 302
Petroleum
in nutrition of micro-organisms,
412-3
origin, 49, 110-1, 127-30, 173-4, 201
porphyrins in, 111, 201-2
Pfliiger, E., 82-4, 419-20
494
INDEX
Phosphorus compounds, inorganic,
205-6, 209
Photoautotrophs
evolution, 442-5, 449
metabolism, 162, 263, 445-8, 455-64
not primitive, 111, 406-7
Photosynthesis (cf. Photoauto-
trophs)
effect on atmosphere, 156-9, 446-
50, 463
production of organic com-
pounds, 109-13, 130, 156-9
Planets, 51-3, 56, 59-60, 69
carbon compounds on, 117-22, 125
origin of, 131-4, 136-42
Plasteins, 266
Plastids, 269, 272
Plato, 4-5
Plotinus, 8
Polarised light, 185, 194-5
Polymerisation of
acetaldehyde, 177
amino acids, 211-3, 216, 266
formaldehyde, 163, 198, 211
glycolic aldehyde, 164
hydrocarbons, 67, 119, 16970,
174, 176, 182-3
hydrocyanic acid, 213
mercaptans, 184
nitriles, 213-5
other organic compounds, 97,
153, 163, 177, 180, 186, 216, 266
Polynucleotides, 100, 203, 209, 288,
302. 341
Polypeptides
abiogenesis, 96, 208-17, 302
structure, 231, 236, 241-2, 245
Porphyrins
abiogenesis, 189, 201-2
biosynthesis, 201-2, 334, 361, 391-2
in enzymes, 372, 439, 441
in petroleum, 111
as photosensitisers, 439, 443-6
Pouchet, F., 26-8, 37, 44
Prokopovich, Theofan, 11-2
Proteins
amino acid composition and
sequence, 232-52
biosynthesis, 86, 259-90, 360, 391-2,
399. 413
in coacervates, 305-11
conjugated, 237, 245-7
denaturation, 67-8, 254-5, 378
Proteins — cont.
'living' and 'dead', 82-4
meaning of word, 229-33, 348-9
three-dimensional structure, 252-
60
X-protein of tobacco mosaic virus,
276-7, 279
Protoplasm
asymmetry in, 196
destruction by radiation, 67-8
models of, 88-91
organisation, 37, 317-23, 331-2, 379
origin, 74, 85-6, 97
proteins of, 68, 82-4
structure, 76, 87-9, 231, 311-21
use of term, 230-1
vitrification, 61
Purine and pyrimidine bases
in nucleotides, 279-80, 282-3, 401
synthesis, 203-5, 216
Radioactivity, 79, 81-2, 94, 155-6,
165-6, 168-9, 174-5, 333
Redi, 17, 37
Respiration
a co-ordinated process, 364-5, 377-8
glycolytic systems in, 114, 467-70
integration in metabolism, 386,
400, 420, 422
ontogenesis, 436
origin, 464-76
oxidative mechanisms in, 470-5
Schafer, E. A., 92-4
Schelling, P., 24
Schorlemmer, C, 108, 230
Schroder, H., 26, 28-9
Schulze, F., 25-6
Schwann, T., 25, 29
Self reproduction of
living systems, 338-9, 350, 360, 362
molecules, 97-9, 389
'moleculobionts', 96-7
nucleic acids, 284-9
nucleoproteins, 217, 232
proteins, 231-2, 259, 261-3, 278
viruses, 274
X-protein, 276
Solar radiation {cf. Ultraviolet
radiations), 161-2, 180, 197, 438
in metabolism, 438, 442-3
Spallanzani, 22-3, 36
INDEX
495
Spontaneous generation, 1-46, 69,
73. 77-8. 80
Standardisation
of amino acids, 239-40
of energy metabolism, 434
of metabolic materials, 391
Stationary open systems, 101, 321-35,
337-8, 352, 356-60, 371, 389-90
Sulphur compounds, inorganic, 141-3,
184, 205, 213-4, 451-5
Symbiogenesis, 85-6
Timiryazev, K. A., 35, 93
Tricarboxylic cycle (Krebs), 337, 380,
386-7, 392, 465-7
Tyndall, J., 73-4
Ultraviolet radiations
and chemical evolution, 79, 94,
97, 143, 162, 175, 180-5, 188,
194-5, 202, 205, 209, 333, 335
effects on organisms, 62-8, 188
Virus, 37, 96-8, 259, 273-9
Terekhovskii, M., 23, 37 Vitalism, 32, 44, 46-7, 109
Thomson, W. (Lord Kelvin), 45, Volcanic effects, 49, 58, 81,
54 129-30, 142, 160, 168, 175
112.
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