Manfred EigenManfred Eigen was a German biophysicist who won the 1967 Nobel Prize in chemistry for his work on fast chemical reactions. He received his doctorate in 1951. One of his advisors at Göttingen was Werner Heisenberg. His major contribution to the origin of life was the idea of a chemical hypercycle, the cyclic linkage of reaction cycles as an explanation for the self-organization of prebiotic systems. This is a generalization of the citric-acid cycle at the heart of respiration in humans and in a slightly different form, all living things. Hans Krebs won the Nobel Prize in 1953 for his discovery of this and other related cycles (glycoxylate cycle and urea cycles). The citric acid cycle provides the energy for metabolism, which some think may have been the first step in abiogenesis, the creation of life from non-living organic chemicals. Each step in the cycle involves a catalyst (an enzyme) that enables the step. At the end of the cycle, the fundamental energy-carrying molecule ATP (adenosine triphosphate. or GTP, the guanosine equivalent) is released, providing the energy to drive all the biomachinery of a cell. Eigen's hypercycle is autocatalytic, one of the handful of requirements cited as necessary for abiogenesis, the transition from non-life to living things. In his 1987 book, Steps Toward Life (English edition 1992), Eigen laid out his ideas on the origin of life. They are important because Eigen explains why he denies Jacques Monod's "apotheosis of chance", and as a result Eigen denies the role of chance in Darwinian evolution itself. He also tells us of the amazing insights of Thomas Mann anticipating molecular biology in his great book The Magic Mountain...
The title of this book can be taken in two ways. First, the steps alluded to might be those first steps that evolution took — or ascended — towards the lowest level of life. For biologists, this first level is the cell, the smallest unit of autonomous life, and thus a forerunner of the single-celled organisms alive today. Fossils have revealed that this first stage of life had long been passed three thousand million years ago. The pre-cellular phase, which cannot have taken longer than the first thousand million years of our planet’s existence, was astoundingly rich in invention and innovation. The most recent thousand million years have been no less extravagant: during this time, Nature has poured over the Earth a seemingly infinite wealth of species out of the cornucopia of evolution. So the fact that evolution is continuous in no way implies that it proceeds at an unchanging rate. Changes are prepared gradually, and then, suddenly, they break through and raise development to a new level. The transformation occurs sometimes in small steps, and sometimes in jumps which express a successful adaptation and often a completely new principle of operation. This leads us on to the second possible interpretation of our title: steps which we ourselves take towards an understanding of the processes of life. Our insight also develops in steps on the large and on the small scale. This aspect is in fact the main aim of this book, that is, to make the principles of evolution clear and comprehensible, and to incorporate them into a unified physical world-view. Molecular biology, which arose in the middle of this century' from the disciplines of biochemistry and molecular structure determination, has gathered a momentum undreamed of at the outset of its short history. It is perfectly appropriate to speak of 'the era of molecular biology’. There is no shortage of excellent descriptions of this modem subject, with all its discoveries and the insight it has gained into structures and reaction mechanisms in biology. The only thing lacking in this new knowledge is its integration into a general understanding of Nature. So far, such an attempt has been undertaken only once, by Jacques Monod. This was a fascinating and ambitious attempt, in which Monod did not shrink from drawing philosophical conclusions. It culminated in an apotheosis of chance. According to Monod, life can only be understood existentially. It can of course be reconciled with the laws of Nature, but it cannot be deduced from them. It is a pure creation from the nothingness of chance, not the revelation of a plan embodied in natural law.In his chapter How does information arise?, Eigen makes a clearconnection between If it really were to emerge that there is only ‘pure chance, absolutely free but blind, at the very root of the stupendous edifice of evolution’, then this book would be superfluous. Our only task would be to report bald facts, dates, structures, and mechanisms. This would relegate biology to an existential enclave in the world-edifice of physics. This book takes up the theme of Monod, whose plain language put many issues into clear perspective. But we shall not persist in proclaiming the omnipotence of chance, which has ruled over physics on the microscopic level ever since Maxwell and Boltzmann. In his inaugural lecture at the University of Zurich in December 1922, Erwin Schrödinger declared: ‘Physical research has shown clearly and unambiguously that for at least the vast majority of physical processes, whose regularity and reproducibility have led to the postulate of general causality, the common root of their strict, law-like behaviour— is chance.' These were the years before the Uncertainty Principle of quantum mechanics established chance as one of the foundations of physics. In biology, chance is reflected even at the macroscopic level: ‘selection’ implies that single, elementary events, determined by chance, are amplified autocatalytically up to visible numbers. None the less, law-like principles are also at work, and these are reflected just as much in the phenomena regarded as typically biological as in those associated with classical physics. The arguments to be put forward here are based upon exact mathematical models and upon experimental studies of biological material. This book is intended to communicate new discoveries. The reason for its being written is similar to that for the writing of Charles Darwin’s The Origin of Species. Darwin’s view is accepted, just as the role of chance is accepted. However, this role will be interpreted in a way quite different from that current in biology. The starting point for our discussion will be the epoch-making discovery made in 1953 by Francis H. C. Crick and James D. Watson, which ushered in the era of molecular biology. This was not so much the first description of the structure of deoxyribonucleic acid (DNA), based upon X-ray analysis, as the recognition that DNA is the molecule of heredity and that its structure holds the key to the understanding of heredity’s molecular mechanism. The long-sought- after transition from chemistry to biology had been found. DNA is in itself a chemical substance, yet it is more than just a large molecule. By virtue of its chemical nature, DNA is an information store. This property, which goes beyond mere chemistry, is the determining force for everything else in biology. We shall come to discuss this in detail, even though this book is not intended as an introduction to molecular biology. Neither is it intended to describe the whole of evolution. Our performance will show just one act of this grand spectacle, the act spanning the period from the first nucleic acid molecules to the first cell, the period during which the transformation of inanimate to living matter took place. Ten chapters are dedicated to this ‘day of creation’, a day that lasted some five hundred million years. Each chapter is preceded by a quotation from the novel The Magic Mountain, by Thomas Mann. The Magic Mountain appeared in 1924, when molecular biology was unheard of. So what is the relevance of these quotations? This collection, selected and compressed, will convey the impression — perhaps more strongly than does the chapter ‘Research’ in The Magic Mountain — that Thomas Mann clearly occupied himself in great depth with the question that makes up the central theme of this book. It is that of the transformation of ‘that nature, which did not even deserve to be called dead, because it was inorganic’ into the ‘simplest living organism’. And the reader will notice that Thomas Mann’s reflections about life represent more than an aesthetic, literary counterpoint to the tenor of this book. In the person of Hans Castorp, who dissects the living organism into smaller and smaller parts, Mann searches for the smallest living entities below the level of the living cell. ‘Those were the genes’. But, he asks, can their ‘elementary nature be established’? What do they look like ‘after yet more light on the subject [is] forthcoming’? Mann reaches the conclusion that genes cannot be elementary structures in the chemical sense, but must in turn themselves have been assembled. In the manner of Hegelian dialectic, he sets up a contradiction, with the thesis that the elementary particles of life, genes, ‘if they determine the order of life, ... must be organized’ set against the antithesis that ‘if they were organized, then they could not be elementary, since life depended upon organization’. He proceeds to resolve the contradiction with the synthesis: ‘however impossibly small they were, they must themselves be built up, organically built up, with the order of life’. He even says what they were made of: ‘molecular groups, which represented the transition between vitalized organization and mere chemistry’. All this Thomas Mann wrote, as his diaries show, in 1920. Since 1953, we have known how genes are built up, and how, within them, the transition from inanimate matter to the ‘blueprint of life’ takes place. The sub-units of genes are ‘elementary’ molecular groups in the chemical sense, chemical units. Only when they are linked up in the DNA molecule does a new, life-specific quality arise: information. Indeed, DNA is equipped with the most conspicuous properties of life. It has a memory, it can reproduce itself, it can mutate during reproduction and thus adapt itself by evolution, and by virtue of the metabolism of the cell it is prevented from sinking into a state of chemical equilibrium, which would exclude the possibility of life. This little unit of life, says Mann, 'far below microscopic size’ can grow spontaneously ‘according to the law that each could bring forth only after its kind’, and it possessed ‘the property of assimilation’ (adaptation) — all of these ‘characteristics of life’. Any of these quotations would befit the title-page of a modem textbook of molecular biology. Normal | Teacher | Scholar