Some Like It Hot, But Not the First Biomolecules 
Jeffrey L. Bada and Antonio Lazcano 
"Science", Jun 14 2002, vol. 296, s. 1982-1983.

Ever since the pioneering work of Aleksandr Oparin and John Haldane nearly a century ago, the prebiotic soup theory has dominated
thinking about how life emerged on Earth (1, 2). According to the modern version of this theory, organic compounds accumulated in the
primordial oceans and underwent polymerization, producing increasingly complex macromolecules that eventually evolved the ability to
catalyze their own replication (see the figure). But is this really how life originated? And what were the conditions that favored its
emergence? 

Experimental support for the prebiotic soup theory was first provided in 1953 by Stanley Miller, who demonstrated that important biomolecules
such as amino acids could be synthesized under simulated early-Earth conditions. The discovery of extraterrestrial amino acids in the
Murchison meteorite in 1970 showed that reactions like those in Miller's experiment (involving ammonia, hydrogen cyanide, and aldehydes or
ketones) occurred on meteorite parent bodies early in the history of the solar system. 

The inventory of organic compounds on the early Earth may thus have been derived from a number of sources: Earth-based syntheses,
asteroid and comet impacts, and the accretion of meteorites and interplanetary dust particles. These abiotic, monomeric organic compounds
would have accumulated in the early oceans, providing the raw material for subsequent reactions. Eventually these reactions would have led to
life as we know it: membrane-enclosed systems of polymers such as nucleic acids and proteins, the core molecules involved in the central
biological functions of replication and catalysis. 

For monomers in the early oceans to undergo polymerization, a thermodynamically unfavorable process, concentration of the soup
constituents, would have been required. Experimental evidence suggests that clays, metal cations, and imidazole derivatives, among others,
may have catalyzed prebiotic reactions, including polymerization. Selective absorption of molecules onto mineral surfaces has been shown to
promote concentration and polymerization of various activated monomers in the laboratory (3). Because absorption involves the formation of
weak noncovalent bonds, mineral-based concentration would have been most efficient at low temperatures (4). Other processes such as
evaporation of tidal lagoons and eutectic freezing of dilute aqueous solutions may also have assisted concentration. The latter process is
particularly effective in the nonenzymatic synthesis of oligonucleotides (5). 

As polymerized molecules became larger and more complex, some of them began to fold into configurations that could bind and interact with
other molecules, expanding the list of primitive catalysts that could promote nonenzymatic reactions. Some of these catalytic reactions,
especially those involving hydrogen-bond formation, may have assisted in making polymerization more efficient. As the variety of polymeric
combinations increased, some polymers may have developed the ability to catalyze their own imperfect self-replication and that of their
molecular kin. This would have marked the appearance of the first molecular entities capable of multiplication, heredity, and variation, and thus
the origin of both life and evolution. 

This scheme is necessarily speculative but has an intrinsic heuristic value: Experimental models can be developed to construct a coherent
narrative of this evolutionary sequence. The chemical nature of the polymers used by the first self-replicating entities remains uncertain, but
threose-based RNA analogs and peptide nucleic acid molecules are possible contenders (6-8). It is generally thought that the first living
molecular entities evolved into the RNA world, which was in turn a stepping stone to the DNA/protein world of modern biochemistry. 

Low temperatures are the most favorable for the long-term survival of organic compounds (9), especially those carrying genetic information,
and for the stability of catalytic polymer configurations. Studies of fossils have shown that ancient DNA is preserved for ~100,000 years in
cool, high-latitude environments, compared with only 1000 to 10,000 years in warmer, lower latitude environments (10, 11). RNA is much more
fragile (12). Although the survival of nucleic acids may be extended by encapsulation into hydrocarbons, such as amberlike resins (10), it is
unknown whether this would have been important in enhancing the stability of genetic molecules in early biotic systems. 

The prebiotic soup scenario thus suggests that the first living entities appeared, and evolved through the RNA world to DNA/protein
biochemistry, when Earth was cool rather than boiling hot. Because of the reduced luminosity of the young Sun, Earth may indeed have been
completely covered with ice during its early history (13). The first self- replicating molecular entities may have developed under these
conditions from the prebiotic organic ingredients. 

In the last decade, the validity of the prebiotic soup theory has been questioned, particularly with respect to the robustness of polymer
synthesis. An alternative "metabolist" theory has been proposed (14-16), although it is not a new idea (17). According to this theory, the first
living system on Earth was a primitive metabolic life characterized by a series of self-sustaining reactions based on monomeric organic
compounds made directly from simple constituents (CO2, CO) in the presence of metal sulfide catalysts. A primitive type of reductive citric acid
cycle is often cited as a model. According to this theory, life in its beginning was nothing more than a self-sustaining chain of chemical
reactions associated with mineral surfaces, with no requirement for genetic information. Metabolic life is thus rightfully referred to as "life as we
don't know it" (18). 

Self-sustaining autotrophic chemical reactions could have arisen in any environment, as long as the reactant/product molecules survived long
enough to continue to be part of the reaction chain. Proponents of this scenario, however, generally favor hydrothermal environments [for
example, see (19)]. Various metabolic reaction schemes have been proposed and investigated, but none have been demonstrated to be
autocatalytic. Nor are there any empirical indications that this is even possible in a prebiotic context (20). 

Furthermore, most of the proposed reactions are probably not unique to hydrothermal settings and would also occur at lower temperatures,
albeit at slower rates (21). Exceptions may include the formation of short peptides from amino acids. This reaction becomes thermodynamically
more favorable with increasing temperature, but peptide bonds are also rapidly hydrolyzed at elevated temperatures (22). The steady-state
concentration of peptides under hydrothermal conditions is therefore problematic. 

If self-sustaining reaction chains did arise on early Earth, they could have played an important role in enriching the prebiotic soup in molecules
not readily synthesized by other abiotic reactions or derived from space. The metabolist theory can thus be viewed as a component of the
prebiotic soup theory (see the figure). But regardless of its initial complexity, autocatalytic chemical-based metabolic life could not have
evolved in the absence of a genetic replication mechanism ensuring the maintenance, stability, and diversification of its components. In the
absence of hereditary mechanisms, autotrophic reaction chains would have come and gone without leaving any direct descendants able to
resurrect the process. 

Life as we know it consists of both chemistry and information. If metabolic life existed on the early Earth, converting it to life as we know it
would have required the emergence of some type of genetic information system. Polymer stability would have been critical as an autocatalytic
reaction system advanced to the point of synthesizing information- carrying molecules, such as nucleic acids, which deteriorate rapidly at
elevated temperatures (10, 12). As metabolic life evolved closer to modern biochemistry, it would likely only have been feasible in cool
environments. 

Proponents of a high-temperature transition from purely chemical reactions to the first autonomous self-replicating entities and their evolution
into cellular organisms often assert that the universal tree of life appears to be rooted in hyperthermophilic (high-temperature) organisms.
However, this argument is flawed. First, there is disagreement about whether the deepest branches in the tree of life are indeed occupied by
heat-loving organisms (23). Second, primitive stages of life that may have existed before protein biosynthesis was invented are not amenable to
molecular phylogenetic analysis. Finally, alternative mechanisms can explain the early emergence of heat-loving organisms. For example, they
may have been the survivors from early Archean high- temperature regimes generated by severe impact events (24). 

If the transition from abiotic chemistry to the first biochemistry on the early Earth indeed took place at low temperatures, it could have occurred
during cold, quiescent periods between large, sterilizing impact events (13). But regardless of how the first life arose, it may not have survived
subsequent impacts. Life may have originated several times before surface conditions became tranquil enough for periods sufficiently long to
permit the survival and evolution of the first living entities into the prokaryotic microbes whose remnants may be present in ~3.5-billion-year-
old rocks (25). 

References and Notes 

1. C. Wills, J. Bada, in The Spark of Life: Darwin and the Primeval Soup (Perseus, Cambridge, MA, 2000). 
2. It has also been proposed that life began elsewhere and was transported to Earth, but this only shifts the problem of the origin of life to a
different location. 
3. J. P. Ferris, A. R. Hill, R. Liu, L. E. Orgel, Nature 381, 59 (1996).  
4. S. J. Sowerby, C.-M. Mörth, N. G. Holm, Astrobiology 1, 481 (2001). 
5. A. Kanavarioti, P. A. Monnard, D. W. Deamer, Astrobiology 1, 271 (2001). 
6. K.-U. Schöning et al., Science 290, 1347 (2001). 
7. P. E. Nielsen, Origins Life Evol. Biosphere 23, 323 (1993). 
8. K. Nelson, M Levy, S. L. Miller, Proc. Natl. Acad. Sci. U.S.A. 97, 3868 (2000). 
9. M. Levy, S. L. Miller, Proc. Natl. Acad. Sci. U.S.A. 95, 7933 (1998). 
10. H. N. Poinar, M. Höss, J. L. Bada, S. Päabo, Science 272, 864 (1996). 
11. I Barnes, P. Matheus, B. Shapiro, D. Jensen, A. Cooper, Science 295, 2267 (2002). 
12. T. Lindhal, Nature 362, 709 (1993). 
13. J. L. Bada, C. Bigham, S. L. Miller, Proc. Natl. Acad. Sci. U.S.A. 91, 1248 (1994). 
14. G. Wächtershäuser, Prog. Biophys. Mol. Biol. 58, 85 (1992). 
15. ------, Proc. Natl. Acad. Sci. U.S.A. 91, 4283 (1994). 
16. H. J. Morowitz, J. D. Kostelnik, J. Yang, G. D. Cody, Proc. Natl. Acad. Sci. U.S.A. 97, 7704 (2000). 
17. M. Ycas, Proc. Natl. Acad. Sci. U.S.A. 41, 714 (1955). 
18. G. Wächtershäuser, Science 289, 1307 (2000). 
19. G. D. Cody, N. Z. Boctor, R. M., J. A. Brandes, H. Morowitz, H. S. Yoder, Geochim. Cosmochim. Acta 65, 3557 (2001). 
20. L. E. Orgel, Proc. Natl. Acad. Sci. U.S.A. 97, 12503 (2000) [Medline]. 
21. A relevant example is petroleum formation. Petroleum is produced from sedimentary organic matter by a series of geochemical reactions that
take place at temperatures of 50° to 175°C over time scales of several million years. At hydrothermal vent temperatures of 300° to 350°C, these
reactions are much more rapid, and petroleum may be produced in periods as short as 100 years. On a global scale, however, the amount of
hydrothermal petroleum is small compared with that generated at lower geologic temperatures. 
22. A. W. Flegmann, R. Tattersall, J. Mol. Evol. 12, 349 (1979). 
23. C. Brochier, H. Phillippe, Nature 417, 244 (2002). 
24. E. G. Nisbet, N. H. Sleep, Nature 409, 1083 (2001). 
25. J. W. Schopf, in The Cradle of Life: The Discovery of the Earth's Earliest Fossils (Princeton Univ. Press, Princeton, 1999), p. 336. 

J. L. Bada is at Scripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 02093, USA. A. Lazcano is at Facultad de Ciencias, UNAM, 04510 Mexico D. F., Mexico.

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