Life without the double helix: Oparin Revisited by Doron Lancet iewing a Watson-Crick model of Department of Molecular Genetics and the DNA is an exhilarating experience. It Crown Human Genome Center, The Weizmann Vbecomes crystal-clear how the base- Institute of Science, Rehovot, Israel paired double helix allows information to be stored and copied. Yet, in the post-1953 euphoria, scientists were tempted to believe that having such an explicit chemical entity as a functional core of present-day life implies that life began with it. The RNA-world model conjectures that the first chemical entity capable of self-replication was a base-paired polynucleotide. The present paper highlights reasons why this is unlikely to be right, and delineates an alternative scenario that draws upon Oparin’s early teachings. From structure to origin A living cell is an utterly complex molecular machine. Origin of life scientists hope that by understanding its intricacies they will stumble upon an explanation for how it emerged. This aspiration is based on experience with simpler systems. For example, by studying moon rocks it is possible to come up with a mechanism of its formation by a cataclysmic planetary collision. However, this may not be true for entities whose complexity is many orders of magnitude higher. In such cases it is necessary to employ divergent thinking, guided by an assessment of which features are fundamental and which are consequential. It is widely agreed that the most crucial property of living entities is a capacity to generate similes. This attribute underlies the process of evolution and natural selection, and must have been present very early in life’s history. An often stated chicken-and-egg conundrum is that life cannot reach even a most rudimentary level of complexity without self-replication, but that only minimally The Secret of Life 126 127 DNA: MOLECULE OF INHERITANCE Life Without the Double Helix by the religious constraints prevailing in An often stated chicken-and-egg conundrum is that Western nations. The standard Oparin- RNA/DNA World Lipid World: the GARD model Haldane theory 12 puts forward the production life cannot reach even a most rudimentary level of of organic molecules on the early Earth followed by chemical reactions that produced complexity without self-replication, but that only increased organic complexity. This process is perceived to have led eventually to organic minimally complex chemical entities can multiply. life capable of reproduction, mutation, and selection. In this form, the theory has no specification of which molecules were first, or how self replication came about. In fact, it predates by two decades the Watson-Crick complex chemical systems can multiply. breakthrough, and is therefore unbiased by The discovery of DNA, simple in design and its implications. seemingly capable of creating its own copies, The origin of organic molecules and has led to a wide belief that nucleic acids the origin of replication are two separate provide a solution for such an incongruity. problems. Actually, the first may be viewed However, an examination of the structure as a prerequisite for the second. The of DNA and RNA reveals chemical intricacy groundbreaking experiments of Miller and Figure 1 that defies the notion that they were the Urey 13, first published in the same year as 5) Development of “organizers” that allowed first replicators. Even in the present-day DNA’s structure, were specifically aimed at controlled reproduction to ensure that The two dichotomous stereotyped “world” scenarios for Life’s setting, polynucleotides only undergo the first question. They asked how, under resultant split-related daughter cells have origin. Both are likely to be over- replication in the context of its cellular milieu. primitive earth conditions, a sufficient the same chemical capabilities. simplifications, since prebiotic In a primordial chemically-heterogeneous supply of organics was generated to warrant mixtures must have included diverse compounds, and not just scenario, the spontaneous emergence Oparin’s “primordial soup”, the milieu in 6) Beginnings of evolutionary developments one class of substances. Therefore, of sufficient quantities of the required which reactions leading to life are assumed so that a group of cells could adapt to the two scenarios should be taken carbohydrate moiety and nitrogen base to have occurred. Criticism has often changes in the environment over time. to represent opposing concepts. On the one hand, the “RNA/DNA components is unlikely. Also, phosphodiester been aimed at both Miller and Oparin for world” view asserts that life began polymerization is thermodynamically conjecturing a particular set of atmospheric This clear-cut hierarchical scenario was with individual molecules that had a unfavorable, and the repeated building of conditions for the generation of an organic considered for decades an acceptable view relatively complex covalent structure, enabling them to store information, 24 a long second nucleic acid strand on its soup, conditions that may have not actually of how life began. In later years Oparin had instruct the synthesis of other first strand template would require intricate prevailed historically. The present paper guessed that the hypothesized “organizers” molecules, and undergo a complex catalysis 1, 2. For these and other reasons it avoids this controversy, positing that organic in step 5 might include nucleic acids, but chain of chemical steps that resulted in their own replication. On the other has been argued by quite a few authors that compounds could have arisen by a wide clearly he was not thinking in terms of a full- hand – the “lipid world”, a scenario an RNA-like polymer may not have been the variety of processes under a broad spectrum fledge transcription and ribosome-mediated that claims that much before the early seed of life 3, 4. of planetary conditions 14-23. We address translation apparatus, as these would have appearance of RNA-like biopolymers, there existed “non-covalent The breakthrough discovery of Watson only the ways by which the double helix’s been too complex for the primitive stages polymers”40, assemblies of relatively and Crick 5, 6 led to the practical extinction of discovery affected scientific views on the invoked. Oparin had the insight to consider small molecules, capable of mutual alternative hypotheses. The beauty of DNA earliest replicators. the possibility of simile generation based association by weak chemical forces, including, but not limited to replication was so compelling that any other According to Oparin’s teachings the on a web of chemical interactions, namely hydrophobic interactions 34. In the “dirtier” pathway suddenly looked untenable. following steps have happened en route to what would be called nowadays a prebiotic realm of this scenario, information Yet, in view of the problems posed above, it early life: metabolism-like network 25-27. Self replication was contained in an assembly’s chemical composition rather than is interesting to ponder the untainted state was thought of as related to the splitting in a molecular covalent sequence of art of origin-of-life research as it existed 1) Random synthesis of simple organic of coacervate droplets, including its entire (Fig. 2), and replication was based prior to 1953. In the process, insight may molecules from atmospheric gases. molecular repertoire, a process conceptually on an assembly’s random fission rather than on orderly templating. In be gained with respect to the dichotomy similar to modern cell division. Oparin the minds of lipid world proponents, between the widely accepted RNA-world 2) Formation of larger, more complex was not influenced by the later realization never was there an early bottleneck model and an emerging, more debatable lipid molecules from the simple organic that within each cell lurks an individual in which one individual molecule Alexander Ivanovich Oparin was responsible single-handedly for (1894-1980), Russian world model for life’s emergence (Fig. 1). molecules. component, DNA, capable of information practically all pivotal life-promoting biochemist. Oparin graduated storage and molecular self-replication. functions. Since it is straightforward from Moscow University in to calculate that uncontrolled organic Oparin revisited 3) Formation of coacervates - unique droplets 7 1917 and became professor chemistry may easily produce 10 of plant biochemistry there The Russian biochemist Aleksandr Ivanovich containing the different organic molecules. The nucleic acid takeover different compounds, and since in 1929. He also helped to Oparin first published his pamphlet The In the post-1953 era, origin of life research the simplest free-living cell has found the Bakh Institute of Origin of Life in 1924 7(reprinted in 8). It was 4) Development of a capacity to take up underwent a revolution, not less significant about 1,000 molecule types, the Biochemistry. As early as 1922 RNA world may be typified by a Oparin was speculating on the only a later expanded version published as a and discharge specific molecules, and than that which affected all of molecular molecular count time-sequence 7 origins of life on Earth and later book 9 that got translated to English shortly maintain a characteristic chemical pattern biology. This revolution hinged on the notion of 10 , 1, 10, 100, 1000 while the published The Origin of Life on 10, 11 lipid world would have a sequence thereafter . In that book, Oparin dealt with or composition.