historical development of origins research

Historical Development of Origins Research

Antonio Lazcano

Facultad de Ciencias, Universidad Nacional Autonoma de Mexico, Apdo. Postal 70-407,Cd. Universitaria, 04510 Mexico D.F., Mexico

Correspondence: [email protected]

Following the publication of the Origin of Species in 1859, many naturalists adopted the ideathat living organisms were the historical outcome of gradual transformation of lifeless matter.These views soon merged with the developments of biochemistry and cell biology and ledto proposals in which the origin of protoplasm was equated with the origin of life. Theheterotrophic origin of life proposed by Oparin and Haldane in the 1920s was part of thistradition, which Oparin enriched by transforming the discussion of the emergence of thefirst cells into a workable multidisciplinary research program.

On the other hand, the scientific trend toward understanding biological phenomenaat the molecular level led authors like Troland, Muller, and others to propose that singlemolecules or viruses represented primordial living systems. The contrast between theseopposing views on the origin of life represents not only contrasting views of the nature oflife itself, but also major ideological discussions that reached a surprising intensity in theyears following Stanley Miller’s seminal result which showed the ease with which organiccompounds of biochemical significance could be synthesized under putative primitiveconditions. In fact, during the years following the Miller experiment, attempts to understandthe origin of life were strongly influenced by research on DNA replication and proteinbiosynthesis, and, in socio-political terms, by the atmosphere created by Cold War tensions.

The catalytic versatility of RNA molecules clearly merits a critical reappraisal of Muller’sviewpoint. However, the discovery of ribozymes does not imply that autocatalytic nucleicacid molecules ready to be used as primordial genes were floating in the primitive oceans,or that the RNA world emerged completely assembled from simple precursors present inthe prebiotic soup. The evidence supporting the presence of a wide range of organic mol-ecules on the primitive Earth, including membrane-forming compounds, suggests that theevolution of membrane-bounded molecular systems preceded cellular life on our planet,and that life is the evolutionary outcome of a process, not of a single, fortuitous event.

It is generally assumed that early philosophersand naturalists appealed to spontaneous gen-

eration to explain the origin of life, but in fact,the possibility of life emerging directly from

nonliving matter was seen at first as a nonsexualreproductive mechanism. This changed withthe transformist views developed by ErasmusDarwin, Georges Louis Leclerc de Buffon, and,

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most importantly, by Jean-Baptiste de Lamarck,all of whom invoked spontaneous generationas the mechanism that led to the emergence oflife, and not just its reproduction. “Nature, bymeans of of heat, light, electricity and moisture”,wrote Lamarck in 1809, “forms direct or spon-taneous generation at that extremity of eachkingdom of living bodies, where the simplestof these bodies are found”.

Like his predecessors, Charles Darwin sur-mised that plants and animals arose naturallyfrom some primordial nonliving matter. Asearly as 1837 he wrote in his Second Notebookthat “the intimate relation of Life with lawsof chemical combination, & the universalityof latter render spontaneous generation notimprobable.” However, Darwin included fewstatements about the origin of life in his books.He avoided the issue in the Origin of Species, inwhich he only wrote “. . . I should infer fromanalogy that probably all organic beings whichhave ever lived on this Earth have descendedfrom some one primordial form, into whichlife was first breathed” (Pereto et al. 2009).

Darwin added few remarks on the originof life his book, and his reluctance surprisedmany of his friends and followers. In his mono-graph on the radiolaria, Haeckel wrote “Thechief defect of the Darwinian theory is that itthrows no light on the origin of the primitiveorganism—probably a simple cell—from whichall the others have descended. When Darwinassumes a special creative act for this first spe-cies, he is not consistent, and, I think, not quitesincere . . .” (Haeckel 1862).

Twelve years after the first publication of theOrigin of Species, Darwin wrote the now famousletter to his friend Hooker in which the idea of a“warm little pond” was included. Mailed onFebruary 1st, 1871, it stated that “It is oftensaid that all the conditions for the first produc-tion of a living organism are now present, whichcould ever have been present. But if (and Oh!what a big if!) we could conceive in somewarm little pond with all sorts of ammoniaand phosphoric salts—light, heat, electricity&c. present, that a proteine compound waschemically formed, ready to undergo stillmore complex changes, at the present day

such matter wd be instantly devoured, or ab-sorbed, which would not have been the casebefore living creatures were formed.” AlthoughDarwin refrained from any further public state-ments on how life may have appeared, his viewsestablished the framework that would lead to anumber of attempts to explain the origin oflife by introducing principles of historicalexplanation (Pereto et al. 2009). Here I willdescribe this history, and how it is guiding cur-rent research into the question of life’s origins.

BACKGROUND

The Search for the PhysicochemicalBasis of Life

In 1805 the German naturalist Lorenz Okenwrote a small booklet titled The Creation, inwhich stated that “all organic beings originatefrom and consist of vesicles of cells.” Severaldecades later the jellylike, water-insoluble sub-stance that was found inside all cells was termed“protoplasm” by the physician Johann E. Pur-kinje and the botanist Hugo von Mohl, wholike others argued that it was the basic physico-chemical component of life. This was followedby Thomas Graham’s 1861 proposal that theprotoplasm was a colloid formed by a homoge-nous, proteinaceous substance, which wasunderstood by many as implying, as ThomasHenry Huxley would write a few years later,that the basic traits of life could be understoodin terms of the chemical and physical propertiesof the molecules that made up protoplasm.

The birth and development of organicchemistry as a prominent scientific field veryrapidly helped to bridge the gap separatingorganisms from the nonliving, paving the wayto biochemistry. In 1827 Berzelius had writtenthat “art cannot combine the elements of inor-ganic matter in the manner of living nature”, butone year later his friend and former studentFriedich Wohler showed that urea could beformed in high yield by heating ammoniumcyanate “without the need of an animal kidney”(Leicester 1974).

Wohler’s work represented the first synthe-sis of an organic compound from inorganic

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starting materials and signals the tremendousadvances in organic chemistry that would playa key role in our understanding of biology.Although it was not immediately recognizedas such, a new era in chemical research hadbeen begun: in 1850 Adolph Strecker achievedthe laboratory synthesis of alanine from a mix-ture of acetaldehyde, ammonia and hydrogencyanide. This was followed by the experimentsof Alexander M. Butlerov showing that thetreatment of formaldehyde with strong alkalinecatalysts, such as calcium hydroxide, leads tothe synthesis of sugars.

The laboratory synthesis of biochemicalcompounds was soon extended to include morecomplex experimental settings, some of whichattempted to explain biological synthesis. Forexample, in 1877 Mendeleyeev, who was skepti-cal of the biological origin of oil, reported thesynthesis of hydrocarbons from hot metalliccarbides and water. By the end of the 19th cen-tury a large amount of research on organic syn-thesis had been performed, which showed theabiotic formation of fatty acids and sugars usingelectric discharges with various gas mixtures.This trend continued into the 20th century byWalther Lob, Oskar Baudish, and others, whoreported the synthesis of amino acids by expos-ing wet formamide (CHO-NH2) to a silent elec-trical discharge and to UV light (cf. Bada andLazcano 2003).

In retrospect, these efforts to producesimple organic compounds heralded the dawnof what is termed today prebiotic chemistry.However, there are no indications that theresearchers who performed these studies wereinterested in how life began on Earth, or inthe synthesis of biochemical molecules underprimitive conditions. It was generally assumedthat that the first living beings had beenautotrophic, plantlike organisms, so the abioticsynthesis of organic compounds did not appearto be a necessary prerequisite for the emergenceof life. These organic syntheses were not con-ceived as laboratory simulations of Darwin’swarm little pond, but rather as attempts tounderstand the autotrophic mechanisms ofnitrogen assimilation and CO2 fixation in greenplants.

Spontaneous Generation or Cosmic Origins?

The Origin of Species was published in 1859, theverysameyear inwhich Pasteur began theexperi-mentsthatwould lead him to disprove spontane-ous generation of living organisms. His resultshadimplicationsthatwent wellbeyondthe limitsof academia. Since the times of Lamarck andBuffon, spontaneous generation had been asso-ciated in France not only with evolutionarytheory but also with secular attitudes and radicalpolitical views. The publication in 1862 of theFrench translation The Origin of Species by thenotorious atheist and republican MadameClemence Royer rekindled the debate. Her ver-sion included a lengthy preface that was, inessence, a fierce attack against the CatholicChurch, by then a powerful ally of NapoleonIII. In such entangled atmosphere, spontaneousgeneration embodied not only support for evo-lution, but also a radical, anticlerical politicalstance (Farley 1977; Fry 2002; Strick 2009).

Pasteur was fully aware of the ideologicalimplications of his discoveries. In a famous lec-ture delivered at La Sorbonne in 1864, he notonly denied the possibility that inanimate mat-ter could organize itself into living systems, butalso stated that “what a victory for materialismif it could be affirmed that it rests on the estab-lished fact that matter organizes itself, takes onlife itself; matter which has in it already allknown forces. Ah! If we could add to it this otherforce which is called life . . . what could be morenatural than to deify such matter? Of what goodwould it be then to have recourse to the idea ofa primordial creation? To what good the wouldbe the idea of a Creator God? . . . if we admit theidea of spontaneous generation, than it wouldnot be surprising to assume that living beings“transformed themselves and climb from rankto rank, for example to insects after 10,000 yearsand no doubt to monkeys and man after 100,000years” (cf. Farley 1977).

Regardless of their political ramifications,Pasteur’s results made it difficult to advocatespontaneous generation as an explanation forthe ultimate origin of life. As a result, a number ofphilosophers and naturalists promptly dismissedthe study of the origins of life as senseless


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speculation, whereas the willful distortion ofPasteur’s results by others raised vitalistic expec-tations once again. Several devoted materialistslike Emil du Bois-Reymond, Karl von Nageli,and August Weismann continued to supportthe idea of spontaneous generation, but others,like Hermann von Helmholtz, felt that theycould side-step the issue by assuming that viablemicrobes—“cosmozoa”—had been delivered tothe primitive Earth by meteorites, thus main-taining the significance of evolution.

Cosmozoa became an alternative for thoseunwilling to accept the idea of a nonmaterialbasis for life, but also for staunch opponents ofevolution like Lord Kelvin, who since 1871 hadargued for the extraterrestrial origin of life.Toward the end of the 19th century, the beliefthat life on Earth had evolved from extrater-restrial organisms elicited a number of proposedmechanisms that could have transported mi-crobes between planets, but little attention wasgiven to the central issue of the actual origin ofthe life forms (Kamminga 1982; Fry 2002).With formidable disregard for plausibility, thepanspermia hypothesis has been repeatedly pro-posed in a variety of contexts, but of course doesnot solve the problem of the origin of life, insteadmerely transferring its origin to another habit-able planet in our galaxy.

Life and the Single Molecule

Not surprisingly, the idea that living organismswere the historical outcome of gradual trans-formation of lifeless matter became widespreadsoon after the publication of The Origin ofSpecies. Despite their diversity, most of theseexplanations went unnoticed, in part becausethey were incomplete, speculative schemeslargely devoid of direct evidence and not subjectto fruitful experimental testing. Although someof these hypotheses considered life as an emer-gent feature of nature and attempted to under-stand its origin by introducing principles ofhistorical explanation, the dominant view wasthat the first forms of life were structurelessdroplets of protoplasm endowed with the abil-ity fix atmospheric CO2 and to use it with waterto synthesize organic compounds.

The ideas of Jerome Alexander, StephaneLeduc, and Alfonso L. Herrera epitomize thistrend. Like many of his contemporaries, theMexican A.L. Herrera was convinced that lifecould be created in the laboratory, and proposedan autotrophic theory known as plasmogenesis.Herrera devoted more than 50 yr to experi-menting with different kinds of substances,attempting to “illustrate the physico chemicalconcomitants of life” (Herrera 1902). At firsthe used mixtures of water and oil (or gasoline)to understand the shape, size and movement ofcell-like structures. He would later refined hisideas and, despite the academic isolation inwhich he worked, developed his theory of“plasmogeny,” which attempted to explainthe origin of primitive photosynthetic proto-plasm. This led him to experiment with formal-dehyde and hydrogen cyanide derivatives likeNH4SCN (Herrera 1942), a combination that wenow know produces sugars and highly coloredpolymers, which unfortunately he mistookfor photosynthetic pigments (Perezgasga et al.2003).

The rapid development of biochemistry andthe characterization of an increasingly largenumber of proteins signaled the idea thatlife could be associated with specific enzymesand that submicroscopic colloidal aggregatesor micelles could show the properties of life.Enzymes were seen as colloidal catalysts, whichled to the hypothesis that entities smaller andsimpler than protoplasm itself could be alive(cf. Fry 2006). In 1917 Felix D’Herelle discov-ered a self-propagating filterable “substance”that attacked and dissolved bacilli, which werelater identified as bacteriophage viruses, andthese supposedly simple submicroscopic parti-cles were assumed to be primordial entities(D’Herelle 1926; Summers 1999).

Some investigators proposed even smallerstructures as primordial. For instance, in a seriesof papers published between 1914 and 1917,the American physicist Leonard Troland sug-gested that the first living entity had been noth-ing more than a self-replicating enzymelikemolecule that had suddenly appeared in earlyoceans. This primordial enzyme was assumedby Troland to be endowed with autocatalytic

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properties that allowed it to self-multiply,as well as having heterocatalytic abilities thatcould alter its surroundings, therefore givingrise to metabolism. Troland’s hypothesis ishindered both by its highly reductionist natureand by the impossibility of empirical analysisof a proposal that depends on the chancelikeassociation of a “living molecule.” As sum-marized by Fry (2006), although Troland hadoriginally proposed a primordial enzyme asthe starting point of life, he modified hishypothesis to speak of a “genetic enzyme”which he eventually identified with nucleop-roteins present in nuclei (Troland, 1914, 1916,1917).

It did not take long for Hermann J. Muller, anAmerican geneticist who would play an impor-tant role in the understanding of Mendelianheredity, to modify Troland’s hypothesis andpropose that the ancestral molecule had been,in fact, a gene. Even more explicitly than Troland,Muller argued that the first living material wasformed abruptly and consisted of little morethan a mutable gene, or set of genes, endowedwith catalytic and autoreplicative properties,which, he hinted, were autotrophic (Muller1922, 1926).

It is easy to understand Muller’s proposalin terms of his commitment to Mendeliangenetics. Muller was a founding member ofThomas Hunt Morgan’s fly room in ColumbiaUiversity, where he had spent several yearsworking with Calvin Bridges, Alfred Sturtevantand Morgan himself, on the linear arrange-ment of genes in the Drosophila chromosomes(Carlson 1981). He had been pondering forsome time on the autocatalytic properties ofchromatin (Ravin 1977), and his appreciationof genetic mutation as the fundamental mech-anism of evolutionary novelties developed at atime when the appeal of Darwin’s ideas on therole of natural selection had diminished.Accordingly, given the appearance of a geneticmaterial capable of replication, mutation andfurther replication of mutant forms, “evolu-tion would automatically follow” (Pontecorvo1982). Muller’s explanation of the origin oflife reveals a mutationist’s attitude, not a Dar-winian one.

Toward the Primitive Soup

In November 1923 a small book titled The Originof Life was published in Moscow by the youngRussian biochemist Alexander Ivanovich Oparin.Like many of his contemporaries, Oparin (1924)accepted the idea of a primordial protoplasmbut proposed that life had been preceded by alengthy periodofabioticsynthesesandaccumula-tion of organic compounds that had led to theaccumulation of what we call today the primitivesoup. Oparin’s central thesis was that the firstorganisms to emerge in the anaerobic environ-ment of the primitive Earth must have been het-erotrophic bacteria.

As a young student at the University ofMoscow, Oparin had joined the laboratory ofAlexeiN. Bakh, an eminent scientistand politicalfigure at the Karpov Physicochemical Institute.There he worked on photosynthesis and, likemost biochemists of his generation, quicklyadopted the idea that metabolism was the out-come of oxidation and reduction reactions thatwere coupled inside cells. By then Oparin wasalso a convinced evolutionist. As an undergrad-uate he had attended the lectures given regularlyby Kliment A. Tymiriazev, a renowed plant phys-iologist, agronomer, and the main advocate ofDarwinism in Russia. Starting in 1865, Tymiria-zev actively promoted Darwin’s idea, an effortthat would play a major role in the secularizationof Russian society, and endeared him to boththe liberal and the revolutionary intelligentsia(Vucinich 1988).

Tymiriazev had left the university and,because of his ill-health, did not teach but lim-ited his meetings with students and colleaguesto small gatherings in his Moscow flat. By thetime Oparin graduated, he had an academicbackground that combined natural history,biochemistry, and plant physiology, a knowl-edge acquired within a research traditionstrongly committed to integral approaches inthe analysis of natural phenomena. He wasnot only familiar with nearly all the literatureon evolution available in Russia but, perhapseven more important, with the Darwinianmethod of comparative analysis and historicalinterpretation of life features (Lazcano 1992).





Like many of his fellow students and col-leagues, Oparin was well acquainted withHaeckel’s work, in which the transition of thenonliving to the first organisms was discussedbut always under the assumption that the firstforms of life had been autotrophic microbes.Analysis of Oparin’s writings shows thatthroughout his entire life he remained faithfulto the Haeckelian division of life into plants,animals and protists. However, from the verybeginning it was impossible for him to reconcilehis biochemical understanding of the sophisti-cation of photosynthesis and the Darwiniancredence in a gradual, slow evolution from thesimple to the complex, with the suggestionthat life had emerged already endowed with anautotrophic metabolism that included enzymes,chlorophyll and the ability to synthesize organiccompounds from CO2 and water.

Because a heterotrophic anaerobe is meta-bolically simpler than an autotrophic one,Oparin argued, the former would necessarilyhave evolved first. Thus, based on the simplicityand ubiquity of fermentative reactions, he pro-posed that the first organisms must have beenheterotrophic bacteria that could not make theirown food but obtained organic material presentin the primitive milieu. To buttress his intu-ition, Oparin needed to show that organicmaterial could form in the absence of livingbeings. Two important pieces of evidence sup-ported his claim that the first organisms weremore likely to have been heterotrophic. First,hydrocarbons and other organic material wereknown to be present in meteorites, and perhapseven in comets. These facts had been knownsince the middle of the 19th century. Second,his proposal was sustained by the striking 19thcentury experimental synthesis of organic com-pounds discussed earlier, including the 1877abiotic formation of long chain hydrocarbonsreported by Mendeleyeev.

Careful reading of Oparin’s 1924 bookshows that, in contrast to common belief, atfirst he did not assume an anoxic primitiveatmosphere. In his original scenario he arguedthat whereas some carbides, i.e., carbon-metalcompounds, extruded from the young Earth’sinterior would react with water vapor leading

to hydrocarbons, others would be oxidized toform aldehydes, alcohols, and ketones (suchas acetone). These molecules would then reactamong themselves and with NH3 originat-ing from the hydrolysis of nitrides (nitrogen-metals),

FemCn þ 4mH2O! mFe3O4 þ C3nH8m

FeNþ 3H2O! FeðOHÞ3 þ NH3

to form “very complicated compounds,” asOparin (1924) wrote, from which proteins andcarbohydrates would form, that would rapidlyform droplets of gel-like material ancestral tothe first cells.

Similar proposals for a heterotrophic originwere also published in 1924 by the geochemistCharles Lipman and the microbiologist R.B.Harvey, although they were not as refined asOparin’s book. Quite significantly, Harveyargued that life had first evolved in a hot spring,where the high temperature would allow chem-ical reactions to proceed at a significant rateeven if the first living beings were endowedwith just a few enzymes. The most significantproposal, however, came from John B.S. Hal-dane, a versatile British biologist who becameone of the founding fathers of neodarwinism.Haldane, like Oparin, argued that the originof life had been preceded by the synthesis oforganic compounds (Haldane, 1929). Basedon experiments by the British chemist E.C.C.Baly, who claimed that he had synthesizedamino acids (Baly 1924) and sugars by the UVirradiation of a solution of CO2 in water (Balyet al. 1927), Haldane suggested that the absenceof oxygen in a CO2-rich primitive atmospherehad led to the synthesis of organic compoundsand the formation of a “hot dilute soup.”Haldane was also influenced by D’Herelle’sdiscovery of phages, and suggested that virusesrepresented an intermediate step in the tran-sition from the prebiotic soup to the first heter-otrophic cells. Life may have remained, wroteHaldane (1929) “in the virus stage for manymillions of years before a suitable assemblageof elementary units was brought together inthe first cell.”

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The Painful Maturation of theHeterotrophic Theory

Oparin belonged to a generation that wasexperiencing the liberal, high-bourgeois cul-tural and scientific circles of Saint Petersburgand Moscow formed by broad-minded scholarslike Pavlov and Vernandsky. He was also encour-aged to develop and support materialistic ideasby the secular atmosphere that followed the1917 Bolschevik revolution. His 1924 bookcan be read as the work of a young, bold, and tal-ented researcher with abundant enthusiasmand free of intellectual prejudices, who wasable to look beyond the boundaries separatingdifferent scientific fields. In retrospect, it canbe also considered the harbinger of his majorwork, a 1936 volume in Russian also called Ori-gin of Life, whose English translation becameavailable 2 years later (Oparin 1938).

The new volume was far more mature andprofound in its philosophical and evolutionaryanalysis, as argued forcefully by Graham (1972),reflecting the changes in a society that wasattempting to develop science, art and culturewithin the framework of dialectical materialism.In his second book Oparin (1938) not onlyabandoned his naıve and crude materialism,but also provided a thorough presentation andextensive analysis of the literature on the abioticsynthesis of organic material. His original pro-posal was revised, leading to the assumptionof a highly reducing primitive mileu in whichiron carbides of geological origin would reactwith steam to form hydrocarbons. Their oxida-tion would yield alcohols, ketones, aldehydes,etc., that would then react with ammonia toform amines, amides and ammonium salts.The resulting proteinlike compounds and othermolecules would form a dilute solution, wherethey would aggregate to form colloidal systemsfrom which the first heteretrophic microbesevolved (Oparin 1938).

Oparin further argued that coacervatedrops represented the optimal mechanism toconcentrate organic material on the primitiveEarth. Coacervates are charged, microscop-ic organic colloidal droplets that can concen-trate organic materials existing in the medium.

Because coacervates form spontaneously whentwo solutions of macromolecules with oppositecharges are mixed, it is quite possible that theywere present in the prebiotic milieu. However,they lack the lipid bilayers, present in all cellsthat retain organic matter in high concentrationsinside a self-constructed boundary. Therefore,coacervates are no longer considered as poten-tially ancestral to life itself. Coacervates werethe favorite model for a considerable time afterOparin’s views became widely known, becausethey were perceived as mimicking the surmisedproperties of precellular systems, but the devel-opment of a more sophisticated understandingof cells led to their dismissal as constituting anystep toward the origins of life (Deamer 1977).

A highly reducing atmosphere would be, forOparin, a mixture of CH4, NH3, and H2O withor without added H2. The atmosphere of Jupitercontains these chemical species, with H2 in largeexcess over CH4. Oparin’s proposal of a primor-dial reducing atmosphere was a brilliant infer-ence from the then fledging knowledge ofsolar atomic abundances and planetary atmos-pheres, as well as from Vernadsky’s idea thatthe early Earth would be anoxic in the absenceof life because molecular oxygen is a productof photosynthesis. As summarized elsewhere(Miller et al. 1997) the benchmark contribu-tions of Oparin’s 1938 book include not onlythe hypothesis that heterotrophs and anaerobicfermentation were primordial and the proposalof a reducing atmosphere for the prebioticsynthesis and accumulation of organic com-pounds, but also the idea that the associationof molecules in precellular systems was a neces-sary prerequisite for their evolution (Miller et al.1997). Oparin was aware that the significance ofcoacervates as laboratory models of such poly-molecular systems had been diminished bymore recent developments. When he visitedMexico to receive an honorary degree thatmy university had granted him, Celia Ramırezand I gave him a copy of Light TransducingMembranes, which David W. Deamer (1977)had edited two years before. “If I had the chanceto start all over again,” he remarked, “I wouldwork on liposomes rather than on coacervatesas models of precellular systems.”





As Farley (1977) wrote, Oparin’s 1938 bookmay be the most significant work ever publishedon the origin of life. It is true that many of hisoriginal ideas have been superseded. However,over the years it has become clear that theopen character of his theory of chemical evolu-tion has allowed the incorporation of newdiscoveries and the development of more accu-rate descriptions of possible primitive scenarioswithout destroying its overall structure andpremises. The heterotrophic theory has notbeen belittled, for instance, but magnified bythe recognition of the key role that geneticmaterial must have placed in the origin of life.Perhaps the most important scientific achieve-ments of Oparin may be his insistence that lifeis the evolutionary outcome of a process andnot of a single event, as well as the methodolog-ical breakthrough that transformed the study ofthe origin of life from a purely speculative prob-lem into a workable multidisciplinary researchprogram.

The Miller-Urey Experiment: The Birth ofPrebiotic Chemistry

The English translation of Oparin’s secondbook caught the attention of biologists such asNorman Horowitz and Cornelius van Niel,but during the next 10 years, while World WarII raged, little progress was made in researchon the origins of life. Driven by his interest inevolutionary biology, Melvin Calvin attemptedto simulate the synthesis of organic compoundsunder primitive Earth conditions using thehigh-energy radiation sources available at theLawrence Berkeley Laboratory. He and hisgroup had limited success: The irradiation ofCO2 solutions with the Crocker Laboratory’s60-inch cyclotron led only to formic acid, albeitin fairly high yields (Garrison et al., 1951).

By the time Calvin and his colleagues pub-lished their results, Harold C. Urey had alreadymoved from Columbia to the University of Chi-cago, where he started to work on cosmochem-istry. He rapidly became convinced the Earth’searliest atmosphere was highly reducing, withCH4 and NH3 instead of CO2 and N2. In 1951Urey gave a seminar dealing with the origin of

the Solar System, and argued that the reducingconditions on the early Earth may have beenimportant to the emergence of life. As he wrotein his 1952 book The Planets: Their origin anddevelopment, “if half the present surface carbonexisted as soluble organic compounds and only10 per cent of the water of the present oceansexisted on the surface of the primitive earth,the primitive oceans would have been approxi-mately a 10 per cent solution of organic com-pounds. This would provide a very favorablesituation for the origin of life” (Urey 1952).

Stanley L. Miller, who had arrived toChicago in the spring of 1951 after graduatingfrom the University of California, Berkeley,attended Urey’s lecture, who like Oparin sug-gested that it would be interesting to simulatethe proposed reducing conditions of the prim-itive Earth to test the feasibility of organic com-pound synthesis. “Urey’s point immediatelyseemed valid to me,” wrote Miller many yearsafterward. “After this seminar someone pointedout to Urey that in his book Oparin had dis-cussed the origin of life and the possibility ofsynthesis of organic compounds in a reducingatmosphere. Urey’s discussion of the reducingatmosphere was more thorough and convincingthan Oparin’s; but it is still surprising that noone had by then performed an experimentbased on Oparin’s ideas” (Miller 1974).

Almost a year and a half after Urey’s lecture,Miller approached Urey about the possibilityof doing a prebiotic synthesis experiment usinga reducing gas mixture. After overcoming Urey’sinitial resistance, he designed three appara-tuses meant to simulate the ocean-atmospheresystem on the primitive Earth by investigatingthe action of electric discharges acting for aweek on a mixture of CH4, NH3, H2, and H2O;racemic mixtures of several protein amino acidswere produced, as well as hydroxy acids, urea,and other organic molecules (Miller 1953,1955; Johnson et al. 2008).

Miller achieved his results by means of anapparatus in which he could simulate the inter-action between an atmosphere and an ocean.To activate the reaction, Miller used an elec-trical spark, which was considered to be a signif-icant energy source on the early Earth in the

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form of lightning and coronal discharges. Theapparatus was filled with various mixtures ofmethane, ammonia, and hydrogen as well aswater, the latter being heated to boiling duringthe experiment. A spark discharge between thetungsten electrodes was produced by a highfrequency Tesla coil with a voltage of 60,000V. The reaction time was usually a week or soand the maximum pressure 1.5 bars. With thisrelatively simple experimental setup, Miller(1953) was able to transform almost 50% ofthe original carbon (in the form of methane)into organic compounds. Although most ofthe synthesized organic material was an insolu-ble tarlike solid, he was able to isolate aminoacids and other simple organic compoundsfrom the reaction mixture. Glycine, the simplestamino acid, was produced in 2% yield (based onthe original amount of methane carbon),whereas alanine, the simplest amino acid witha chiral center, showed a yield of 1%. Millerwas able to show that the alanine was a racemicmixture (equal amounts of D- and L-alanine).This provided convincing evidence that theamino acids were produced in the experimentand were not biological contaminants some-how introduced into the apparatus.

DNA versus Coacervates? The Reshaping ofan Old Debate

The Miller paper (1953) was published onlya few weeks after Watson and Crick’s (1953)classic article revealed their double helix modelfor the structure of DNA. With few exceptions,like Sidney W. Fox’s work on thermal polypep-tides (cf. Fox and Dose 1977), modern attemptsto understand the origin of life have beenshaped by our burgeoning knowledge of DNAreplication and protein biosynthesis. Prebi-otic chemistry and molecular biology beganto converge, albeit slowly, when Oro (1960)showed the remarkable ease with which adeninecould be produced through the oligomerizationof HCN.

Hermann J. Muller quickly used the devel-opments in molecular genetics and the successin prebiotic syntheses to update his gene-firstproposal by arguing that what had emerged in

the primitive oceans had been, in fact, a primor-dial DNA molecule : “. . . it is to be expected thatat last, just before the appearance of life, the veryocean had become, in Haldane’s (1929, 1954)vivid phraseology, a gigantic bowl of soup,”wrote Muller, and added “drop into this a nu-cleotide chain and it should eventually breed!”(Muller 1961). A few years later he would statethat “. . .life as we know it, if stripped of all itssuperstructures, lies in the three faculties pos-sessed by the gene material. These may bedefined as, firstly, the self-specification, afterits own pattern, of new material produced byit or under its guidance; secondly, of perform-ing this operation even when it itself has under-gone a great succession of permanent patternchanges which, taken in their totality, can beof a practically unlimited diversity; thirdly, of,through these changes, significantly and (fordifferent cases) diversely affecting other materi-als and, therewith, its own success in geneticsurvival.” Muller added that “the gene materialalone, of all natural materials, possesses thesefaculties, and it is therefore legitimate to call itliving material, the present-day representativeof the first life” (Muller 1966). In other words,for Muller (and many others) the essence of lifelies in the combination of autocatalysis, hetero-catalysis, and mutability, i.e., evolvability.

Muller’s proposal was brilliantly reduction-ist, and was soon contested by Oparin and othersin a now largely forgotten debate. AlthoughMuller (1947) had once expressed sympathy toOparin’s idea, they soon became engaged in anentangled debate in which science, philosophy,and politics mixed in an excruciating discussionthat was shaped in part by the Cold War atmos-phere (Lazcano 1992, 1995; Fry 2002). In sharpcontrast with Muller’s ideas, Oparin (1938)had argued that the essence of life was metabol-ic flow. For Oparin, life is “a special form of themotion of matter,” always in flow, which includ-ed enzymatically based assimilation, growth,and reproduction, but not nucleic acids, whosegenetic role was not even suspected during the1930s. Biological inheritance was assumed byOparin to be the outcome of growth and divi-sion of the coacervate drops he had suggestedas models of precellular systems, a view that





led Muller (1966) to state that “the RussianOparin has since the early 1930s espoused thisview and has followed the official CommunistParty line by giving the specific genetic materiala back seat.”

Oparin and Muller came from differentscientific backgrounds and almost oppositeintellectual traditions. Their common interestin the origin of life did nothing to assuage theiropposing views and their ideological clashes.Oparin was a convinced evolutionist, and, likemany of his contemporaries, his original genet-ics were pre-Mendelian. Oparin’s Darwinismhad been nurtured by Tymiriazev, who hadfamously identified in 1912, many years beforethe Lysenko affair, Mendelians and mutationistsas the opponents to be defeated in the waragainst anti-Darwinism (Vucinich 1988). ForMuller, who remained bitterly disillusioned byStalin’s regime and Lysenko’s tragic affair, lifecould be so well-defined that the exact point atwhich it started could be established with thesudden appearance of the first DNA molecule.Oparin, on the other hand, refused to admitthat life could arise all at once by a spontaneousgeneration, and argued that it was the outcomeof a slow, stepwise evolutionary developmentalprocess.

Oparin’s refusal to assume that nucleicacids had played a unique role in the origin oflife resulted not only from his unwillingness toassume that life can be reduced to a single com-pound such as the “living DNA molecule”advocated by Muller and others, but also withinthe framework of Cold War politics, his complexrelationship with Lysenko, and his long associa-tion with the Soviet establishment. As shownby his extensive work with RNA-containingcoacervates (Oparin and Yevreinova, 1947;Oparin and Serebroskaya, 1963; Oparin et al.1961, 1963, 1964) and his complete acceptance,based on the suggestions of Belozerskii (1959),Brachet (1959), and others, that RNA couldhave preceded DNA as genetic material, Oparin(1961) eventually acknowledged the role ofnucleic acids in the origin of life and assumed,until the very end, that protein synthesis wasthe evolutionary outcome of the interaction ofprimordial polypeptides and polynucleotides

within the boundaries of precellular systems(Oparin 1972).

Paving the Road to the RNA World

The launching of the Sputnik in 1957 signalednot only the start of space exploration but alsoa new epoch in the study of the origins of life,which acquired a novel perspective, as shownby the publication of Life in the Universe, abook by Oparin and Fesenkov (1961). The firstchapter, written by Oparin, examined the con-ditions under which life was assumed to haveoriginated on Earth, and the rest of the bookby Vasily Fesenkov, an astronomer with consid-erable following in the USSR. The premise thatlife appeared throughout the Universe when-ever the conditions for its appearance werepresent set the tone the book, and reflected opti-mistic views regarding the possibility of inhab-ited planets shared by many astronomers bothin the Soviet Union and in Western countries.By then, the development of space programsand agencies had started to play a key role notonly in transforming the issue of extraterrestriallife into a legitimate scientific question, but alsoto shape the study of origin and early evolutionof life in new ways (Dick 1998; Wolfe 2002;Strick 2004).

If the onset of the so-called Space Age (whichled to substantial funding from NASA to theorigins-of-life community) set the emergenceof living systems within a cosmic context, thework of Elso S. Barghoorn and his studentsand associates pushed the microbial fossil re-cord back in time to the early Precambrian(Cloud 1983). Although it seems that life ap-peared as soon as environmental conditionspermitted, identification of the oldest paleonto-logical traces of life remains a contentious issue.Although it is not possible to assign a precisechronology to the origin and earliest evolutionof cells, the recognition that life is a very an-cient phenomenon runs parallel to the limitsimposed by a geological record that becomesincreasingly blurred as we go back in time(Schopf 1999; Knoll 2003).

Direct information is lacking not only onthe composition of the terrestrial atmosphere

A. Lazcano




during the period of the origin of life, but alsoon the temperature, ocean pH values, and othergeneral and local environmental conditionswhich may or may not have been importantfor the emergence of living systems. However,the lack of detailed understanding of the condi-tions of the primitive environment did notstop prebiotic chemists from attempting thesynthesis of a wide number of compounds ofbiochemical significance under highly reducingconditions but with few other environmentalconstraints. The robustness of this type of chem-istry is supported by the occurrence of most ofthese biochemical molecules in the Murchisonmeteorite, reinforcing, but not proving, theidea that comparable compounds were presentin the primitive Earth (Ehrenfreund et al. 2002).

From the late 1960s onward, however,it became clear that our understanding of theorigin of life was troubled by two major issues:The possibility that the young Earth had beenendowed with a highly reducing atmospherewas viewed with considerable skepticism bymost planetary scientists, whose preference fora CO2-rich atmosphere weakened the assump-tion that the primitive soup had formed by theaccumulation of organic compounds synthe-sized under highly reducing conditions. Sec-ondly, the emergence of nucleic acid-directedproteinsynthesis,which is recognizedas acentralfeature of all extant life, appeared to be an insur-mountable problem. At the time, few molecularbiologists were inclined to evolutionary explan-ations and many, like Muller, relied on chanceevents to understand the basic molecular traitsof cells. As the influential French biologistJacques Monod wrote in his 1970 book Chanceand Necessity, “. . . it might be thought that thediscovery of the universal mechanisms basic tothe essential properties of living beings wouldhave helped solve the problem of life’s origins.As it turns out, these discoveries, by almostentirely transforming the question, have shownit to be even more difficult than it formerlyappeared” (Monod 1971). Monod’s attitudehad far reaching consequences; as summarizedby Fry (2002), it would eventually lead the phi-losopher Karl Popper (1974) and his followersto argue that the emergence of life is “an

impenetrable barrier to science and a residue toall attempts to reduce biology to chemistry andphysics.”

A possible solution to the problem posedby the lack of understanding of the relationshipbetween nucleic acids and proteins was sugges-ted by Carl Woese (1967), Leslie Orgel (1968),and Francis Crick (1968), who independentlyproposed the idea that the first living entitieswere based on RNA as both the genetic materialand as catalyst. Surprisingly, these pioneeringproposals of an RNAworld received little atten-tion. The relationship between evolutionaryissues and molecular biology was slow to de-velop, and during several decades was em-bittered by frequent clashes during whichevolutionary analysis was frequently dismissedas little more than useless speculation.

This skeptical attitude changed with theawareness that genes and proteins are richhistorical documents from which a wealth ofevolutionary information can be retrieved(Zuckerkandl and Pauling 1965). A majorachievement of this approach was the use ofsmall subunit ribosomal RNA as a phylogeneticmarker, which led Carl Woese and his associatesto the construction of a trifurcated, unrootedtree in which all known organisms can begrouped in one of three major cell lineages,i.e., eubacteria, archaeabacteria, and theeukaryotic nucleocytoplasm, all of which sharea common ancestry (Woese and Fox 1977). Thevariations of traits common to extant speciescan be explained as the outcome of divergentprocesses from an ancestral life form that existedbefore their separation of the three majorbiological domains, i.e., the last common ances-tor. Although no evolutionary intermediatestages or ancient simplified versions of the basicbiological processes have been discovered incontemporary organisms, the differences inthe structure and mechanisms of gene expres-sion and replication among the three lineageshave provided insights on the stepwise evolu-tion of the replication and translational ap-paratus, including some late steps in thedevelopment of the genetic code. All of a sud-den, it deemed possible to distinguish the originof life problem from a whole series of other





issues, often confused, that belong to the do-main of the evolution of microbial life.

RECENT RESULTS

So Far from the Origin of Life, so Close tothe RNA World

It is difficult to see how inferences based on uni-versal phylogenies can be extended beyonda threshold that corresponds to a period of cel-lular evolution in which protein biosynthesiswas already in operation, i.e., an RNA/proteinworld. Older stages are not yet amenable tomolecular phylogenetic analysis (Becerra et al.2007). A cladistic approach to the origin of lifeitself is not feasible, because all possible inter-mediates that may have once existed have longsince vanished, and the temptation to do other-wise is best resisted. The most basic questionspertaining to the origin of life relate to muchsimpler entities predating by a long (but notnecessarily slow) series of evolutionary eventsthe oldest branches in universal phylogenetictrees.

Nevertheless, the examination of the pro-karyotic branches of unrooted rRNA trees hadalready suggested that the ancestors of both Bac-teria and Archaea were extreme thermophilesgrowing optimally at temperatures in the rangeof 90oC or above (Achenbach-Richter et al.1987). Rooted universal phylogenies appearedto confirm this possibility, because heat-lovingprokaryotes occupied short branches in the basalportion of molecular cladograms (Stetter 1994).Attempts to correlate the antiquity of hyperther-mophiles with extreme environments such asthose found today in deep-sea vents (Holm1992) or in other sites in which mineral surfacesmay have fueled the appearance of primordialchemoautolithotrophic life forms (Wachters-hauser 1988, 1992) became almost unavoidable.

Wachtershauser’s explicit adherence to KarlPopper’s philosophical stand (Popper 1959)played a major role in his idea that life beganwith the appearance of an autocatalytic two-dimensional autochemolithotrophic metabolicsystem based on the formation of pyrite. Hisinsightful prediction that ferrous sulfide in

the presence of hydrogen sulfide (H2S) is an effi-cient reducing agent should not be understated.Pyrite formation can produce molecular hydro-gen, promote the formation of ammonia fromnitrogen nitrogen, and can reduce a few organicmolecules under mild conditions. However,compared with the surprising variety of bio-chemical compounds that are readily synthe-sized in one-pot Miller-Urey type simulations,the suite of molecules produced under theconditions suggested by Wachtershauser is quitelimited.

Based on the hypothesis that core metabolicprocesses have not changed since the emergenceof life, Morowitz (1992) has argued that inter-mediary metabolism recapitulates prebioticchemistry. He maintains that the basic traits ofmetabolism could only evolve after the closureof an amphiphilic bilayer membrane into avesicle, that is, that the appearance of mem-branes represents the discrete transition fromnonlife to life. According to his hypothesis,reverse Krebs cycle-dependent life appearedwith “minimal protocells” formed by bilayervesicles made up of small amphiphiles and en-dowed with pigments capable of absorbingradiant energy stored as a chemiosmotic protongradient across the membrane.

These and other explanations of the originof life are based on the idea that the emergenceof autocatalytic “metabolic” cycles in the prim-itive Earth was an essential prerequisite for theappearance of genetic systems. According tothis approach, life can be considered an emer-gent interactive system endowed with dynamicproperties that exist in a state close to chaoticbehavior. Some of these proposals reflect a(healthy) reaction against molecular biologyreductionism, as well as the adherence to all-encompassing views based on complexity theo-ries and self-assembly phenomena that are quitepopular among physical scientists. In fact, thebackground of current metabolism-based expla-nations of the origin of life lies not in Oparin’sproposals, but in the attempts to extrapolateto biology the deeply rooted tendency in phys-ical sciences to search for all encompassing lawsthat can be part of grand theory which explainmany, if not all, complex systems.

A. Lazcano




The many examples of self-organizing phys-ical systems that lead to highly ordered structu-res show that, in addition to natural selection,other mechanisms of ordered complexity cancome into play. Self-assembly is not unique tobiology, and may indeed be found in a widevariety of systems, including cellular automata,the complex flow patterns of many differentfluids, in cyclic chemical phenomena (such asthe Belousov-Zhabotinsky reaction) and, quitesignificantly, in the self-assembly of amphi-philic lipid-like molecules in bilayers, micelles,and liposomes (cf. Lazcano 2009). There areindeed some common features among thesesystems, and it has been claimed that they followgeneral principles that are in fact equivalentto universal laws of nature (Kauffman 1993).Perhaps this is true. The problem is that suchall-encompassing principles, if they exist at all,have so far remained undiscovered (Farmer2005).

As discussed elsewhere, the experimentalevidence that has been recently used to arguein favor of the metabolism-first theory is equallyconsistent with a genetic-first description of life(Lazcano 2009). What the metabolic-first ap-proaches require is the confirmation that meta-bolic (or protometabolic) routes can replicateand evolve. So far, there are no indicationsthat this is the case: As summarized by LeslieOrgel in a posthumous paper, theories thatadvocate the emergence of complex, self-organized biochemical cycles in the absence ofgenetic material are hindered not only by thelack of empirical evidence, but also by a numberof unrealistic assumptions about the propertiesof minerals and other catalysts required to spon-taneously organize such sets of autocatalyticchemical reactions (Orgel 2008).

CHALLENGES AND FUTURE DIRECTIONS

The remarkable coincidence between the mono-meric constituents of living organisms and thosesynthesized in laboratory simulations of theprebiotic environment appears to be too strikingto be fortuitous. Although we are far from un-derstanding how life appeared, the available ex-perimental evidence strongly suggest that the

prebiotic environment was already endowedwith a wide range of monomers of biochemicalsignificance, many organic and inorganic cata-lysts, purines and pyrimidines, i.e., the potentialfor template-directed polymerization reaction,and membrane-forming compounds. Never-theless, at present the hiatus between the primi-tive soup and the RNA world is discouraginglyenormous.

There are many definitions of the RNAWorld. However, the discovery of ribozymesdoes not imply that wriggling autocatalyticnucleic acid molecules ready to be used as pri-mordial genes were floating in the primitiveoceans, or that the RNA world emerged com-pletely assembled from simple precursorspresent in the prebiotic broth. Although it istrue that genetic-first proposals do not requireenclosure within compartments, the emergenceof life may be best understood in terms of thedynamics and evolution of sets of chemicalreplicating entities. Whether such entities wereenclosed within membranes is not yet clear,but given the prebiotic availability of amphi-philic compounds this may have well been thecase (Deamer 2002). Indeed, the evidence sup-porting the presence of lipidic molecules in theprebiotic environment and their natural abilityto self-organize into vesicular compartmentsunderlines the significance of theoretical mod-els of simple cells involving an evolving ribozy-mic RNA polymerase (Szostak et al. 2001;Deamer and Dworkin 2005) and increasinglysophisticated laboratory models of precellularsystems (Mansy et al. 2008).

For obvious methodological reasons, experi-mental simulations of prebiotic events have con-centrated on the empirical analysis of singlevariables. The study of more specific conditions,including the laboratory simulation of localizedenvironments suchas volcanic islands, tidalzonesand microenviroments, including liposomes,clays and mineral surfaces, and volcanic ponds,which could have been prevalent in the primitiveenvironment, are likely to yield promising results.It is reasonable to assume that the association andinterplayof different biochemical monomers andoligomers in more complexexperimental settingswould lead to physicochemical properties not





shown by their isolated components (Deameret al. 2002). This is not purely speculative; thatinteractions between liposomes and differentwater-soluble polypeptides lead to majorchangesinthemorphologyand permeabilityof liposomesof phosphatidyl-L-serine, and to a transition ofpoly-L-lysine from a random coil into an a-helixthat shows hydrophobic bonding with the lipidicphase, has been documented in the laboratory(Hammes and Schullery 1970).

Additional examples include experimentalmodels of compartmentalized catalytic RNA(Mansy et al. 2008), which, although they donot necessarily correspond to particular stagesin the origin of life, nonetheless illustrate howindividual components of a system dynamicallyinteract and lead to unexpected new properties.This approach, which falls within the venerabletradition of synthetic biology (Pereto andCatala 2007), complements the attempts towork backward to reduce extant cell genomesand achieve the laboratory synthesis of minimallife forms.

There are inevitable gaps in the story, butreports on the death of the heterotrophic theoryhave been greatly exaggerated. The remarkablecoincidence between the surprising variety ofbiochemical constituents that can be readilysynthesized in experiments simulating the pre-biotic environment and those found in somecarbon-rich meteorites appears to be too strik-ing to be fortuitous. The Earth’s primitiveatmosphere may have not been as stronglyreducing as assumed by the early proponentsof the prebiotic broth, but there is experimentalevidence showing that amino acids can be syn-thesized in a CO2-rich model atmosphere(Cleaves et al. 2008). It is true that the classicalrecipe for cooking a primitive soup needs tobe updated to acknowledge, in an eclectic fash-ion, the contribution of extraterrestrial organiccompounds, the role of catalytic minerals likepyrite, and the synthesis of organic moleculesin hydrothermal vents, however limited it mayhave been, but this poses no threat to the ideaof chemical evolution as a prerequisite to anheterotrophic origin of life.

We will never know how life first appeared.However, the study of the appearance of life is

a mature, well-established field of scientificinquiry. As in other areas of evolutionary bio-logy, answers to questions on the origin andnature of the first life forms can only beregarded as inquiring and explanatory ratherthan definitive and conclusive. This does notimply that all origin-of-life theories and expla-nations can be dismissed as pure speculation,but rather that the issue should be addressedconjecturally, in an attempt to construct not amere chronology but a coherent historical nar-rative by weaving together a large numberof miscellaneous observational findings andexperimental results. It is probably useful toremember the line from Goethe’s Faust thatOparin included in his 1924 book, “My worthyfriend, gray is all theory, and green alone is life’sgolden tree.”

ACKNOWLEDGMENTS

This article was completed during a sabbati-cal leave in which I enjoyed the hospitality ofProfessor Jeffrey L. Bada and his associates atthe Scripps Institution of Oceanography, Uni-versity of California San Diego. Support froma UC Mexus-CONACYT Fellowship is gratefullyacknowledged.

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A. Lazcano




published online June 9, 2010Cold Spring Harb Perspect Biol Antonio Lazcano Historical Development of Origins Research

Subject Collection The Origins of Life

Constructing Partial Models of Cells

et al.Norikazu Ichihashi, Tomoaki Matsuura, Hiroshi Kita,

The Hadean-Archaean EnvironmentNorman H. Sleep

RibonucleotidesJohn D. Sutherland

An Origin of Life on MarsChristopher P. McKay

Characterize Early Life on EarthHow a Tree Can Help−−Deep Phylogeny

RandallEric A. Gaucher, James T. Kratzer and Ryan N.

Primitive Genetic PolymersAaron E. Engelhart and Nicholas V. Hud

Medium to the Early EarthCosmic Carbon Chemistry: From the Interstellar

Pascale Ehrenfreund and Jan Cami

Membrane Transport in Primitive CellsSheref S. Mansy

Origin and Evolution of the RibosomeGeorge E. Fox

The Origins of Cellular LifeJason P. Schrum, Ting F. Zhu and Jack W. Szostak

BiomoleculesPlanetary Organic Chemistry and the Origins of

Kim, et al.Steven A. Benner, Hyo-Joong Kim, Myung-Jung

From Self-Assembled Vesicles to ProtocellsIrene A. Chen and Peter Walde

the Origins of LifeMineral Surfaces, Geochemical Complexities, and

Robert M. Hazen and Dimitri A. Sverjensky

The Origin of Biological HomochiralityDonna G. Blackmond

Historical Development of Origins ResearchAntonio Lazcano

Earth's Earliest AtmospheresKevin Zahnle, Laura Schaefer and Bruce Fegley

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