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The ScientistDecember 1, 2003

Darkness Before the Dawn - of Biology

By Jack Lucentini

In 1953 a University of Chicago graduate student, Stanley Miller, shot electric sparks into an apparatus that circulated water, methane, ammonia, and hydrogen in a closed system. After a week, he identified organic compounds, including amino acids, in the turbid red liquid that resulted.1 The experiment galvanized research into life's origins. Yet for decades afterward, the work has proceeded in fits and starts, as scientists struggled to explain how building-block molecules, scattered throughout a "primordial soup" of the ancient seas, might have gathered themselves into something resembling life.

Fifty years later, researchers see new reasons for optimism. In some ways having moved past building blocks, they have created, under simulated assumed primordial conditions, larger structures and processes akin to those that characterize cells, including simple cell membranes, bits of possible early metabolisms, and crude RNA catalysts. Some investigators even suggest that the creation of artificial cells might be within reach.

LAWYERS AND OCEAN BOTTOMS - Several factors have driven this work, "reenergizing a field that's been around for a long time," says George Cody, a senior research scientist at the Carnegie Institution of Washington, DC. A major factor, he says, was the 1979 discovery of microbes thriving on chemicals released at deep-sea hot springs, or hydrothermal vents. The findings prompted speculation that life originated in similar habitats. A German patent lawyer and biochemist, Günter Wächtershäuser, later developed a detailed theory of how the earliest metabolic cycles could have functioned there. This proposal, in turn, inspired streams of useful experiments, Cody says, despite being controversial. Some, including Cody, don't fully buy it.

Michael J. Russell, a research professor at the Scottish Universities Research and Reactor Centre, credits advances in biochemistry and geochemistry with fueling origins-of-life research. The two approaches seem to be converging, he wrote in a recent commentary, such that "the experimental quest for the recipe for 'protolife' can begin in earnest."2

A possible bit of this recipe accompanied the commentary. Martin M. Hanczyc and colleagues at Massachusetts General Hospital in Boston reported that clay particles catalyzed the conversion of molecular precursors into bilayer membrane sacs containing RNA. Forcing these sacs through narrow pores made them divide, allowing cycles of division and regrowth.3 The artificiality of this extrusion procedure, the authors concede, probably means it has no natural analogue. Russell, more optimistically, suggests that porous clays near relatively cool hydrothermal vents might permit such processes. The "first cells would have had to divide or bud and, at the same time, pass on a code for growth and maintenance," he wrote.

The findings also show how "the mineral-water interface is likely to have been important in organizing some of the compounds" of early life, notes David Deamer, a professor of chemistry and biochemistry at the University of California, Santa Cruz. This observation echoes other research, based on Wächtershaüser's theory, which suggests early metabolic cycles also might have occurred at such interfaces. Wächtershaüser developed the proposal by calculating backward from modern organisms' metabolic cycles, to derive a putative original cycle. This cycle predated cells, he contends, taking place first at mineral surfaces, which served both as catalysts and as stages to bring the reactants together. Only later did membranes encapsulate the reacting chemicals and drift off these surfaces for an independent life.

Wächtershaüser claims the key primordial metabolic cycle resembled the reductive citric acid cycle, which operates in vent-dwelling archaebacteria. It is essentially the reverse of the citric acid cycle, which generates energy and expels carbon dioxide. Wächtershäuser's proposed cycle takes up carbon monoxide as a carbon source for the organism, and runs on energy from oxidation of vent minerals.

Other researchers, including Claudia Huber of Munich Technical University, who works with Wächtershäuser, and Cody, who works separately, have conducted experiments that they say support key parts of the theory. They have played out parts of the cycle under conditions designed to mimic those near vents, albeit with more concentrated reactants.4 Under similar conditions, they have demonstrated amino acid synthesis, and peptide assembly and disassembly, all crucial metabolic processes.5 In a surprise side reaction, Wächtershäuser says, this disassembly also produced a precursor to purines, components of nucleic acids, suggesting these might have co-evolved with peptides. "It's exciting the way you can open a door, come into a room and find a hundred doors," Wächtershäuser remarks.

NEW RECIPE, NEW SOUP - The vent hypothesis has stolen some attention from the prevailing "primordial soup" model of life's origins, which burst onto the stage with Miller's experiment. It held that life originated in the oceans by feeding on small, organic molecules and getting energized by a highly reducing atmosphere and energy sources such as sunlight or lightning. Vent theories gained currency after it emerged that conditions nearer the ocean surface could have been hostile to life. The atmosphere might have been less reducing than once supposed, and constant meteor and comet bombardments could have shattered each fragile new beginning. The vents might have provided a safer environment.

But debate abounds. The vent hypothesis itself is actually several hypotheses. Wächtershaüser claims that the first organisms were autotrophs, feeding off chemical energy from inorganic chemicals spewing from vents. This separates him from virtually all other researchers, who contend that early organisms were heterotrophic, nourishing themselves on small organic molecules. "If we've been more and more successful at showing how the natural world comes up with these interesting [organic] substrates, why would the first organism completely ignore that?" Cody remarks.

Other researchers stick to the soup recipe. Wächtershaüser's model is "not relevant to the question of the origin of life as we know it," writes Jeffrey L. Bada, director of the NASA Specialized Center of Research and Training in Exobiology at the Scripps Institution of Oceanography in La Jolla, Calif., in an E-mail. Bada has argued that the vents' high temperatures would destabilize organic compounds. He also disputes findings, sometimes cited in support of the vent scenario, that heat-loving organisms occupy the evolutionary tree's deepest branches.6

Bada, Miller, and others advocate an updated version of the soup theory. Miller recently proposed that although a strongly reducing primordial atmosphere, crucial to the original theory, is now in doubt, a more weakly reducing one would suffice. His team irradiated a weakly reducing mixture of putative, primordial atmospheric gases with protons and obtained, they wrote, bioorganic compounds in amounts comparable to those that a strongly reducing atmosphere would yield.7 Bada also has explored the possibilities that meteorites might have deposited organic compounds on Earth, and that repeated freeze-thaw cycles on the planet might have stimulated organic compound synthesis.

ULTIMATE PROOF OF LIFE - The debate is "tending to fuel good science," says Matthew Levy, a postdoctoral researcher at the University of Texas at Austin. He participates in yet another line of research, the evolution of RNA. Driving this work is a belief that RNA might have been the first self-replicating system, because its ability to act as both enzyme and coding template would resolve a conundrum over which one came first. Researchers have made some progress in artificially "evolving" short oligonucleotides that can catalyze their own replication and perhaps such biologically relevant functions as redox chemistry.8

Other factors boosting origins-of-life research include improved technology, which lets researchers better assess synthesized organic molecules. Such methods have come a long way since the paper chromatography of Miller's 1953 experiment.1 "The technology has made performing tasks of chemistry, which used to be daunting, routine," says Jason Dworkin, an astrobiologist at NASA's Goddard Space Flight Center, Greenbelt, Md.

Other recent advances, some scientists suggest, may put the ultimate origins-of-life experiment within reach: the creation of an artificial cell. Deamer has taken steps in this direction. He and colleague Pierre-Alain Monnard enclosed a strip of template DNA and polymerase in a bilayer lipid membrane; they reported that the sac drew in ribonucleotides surrounding it to synthesize RNA.9 A replicating, evolving system could be a next step, Deamer and colleagues contend: "The goal of future investigations will be to fabricate artificial cells as models of the origin of life."


1. S.L. Miller, "A production of amino acids under possible primitive earth conditions, " Science, 117:528-9, 1953.

2. M.J. Russell, "The importance of being alkaline," Science, 302:580-1, Oct. 24, 2003.

3. M.M. Hanczyc et al., "Experimental models of primitive cellular compartments: encapsulation, growth and division," Science, 302:618-22, Oct. 24, 2003.

4. G.D. Cody et al., "Primordial carbonylated iron-sulfur compounds and the synthesis of pyruvate," Science, 289:1337-40, 2000.

5. C. Huber et al., "A possible primordial peptide cycle," Science, 301:938-40, Aug. 15, 2003.

6. J.L. Bada, A. Lazcano, "Some like it hot, but not the first biomolecules," Science, 296:1982-3, 2002.

7. S. Miyakawa et al., "Prebiotic synthesis from CO atmospheres: implications for the origins of life," Proc Natl Acad Sci, 99:14628-31, 2002.

8. S. Tsukiji et al., "An alcohol dehydrogenase ribozyme," Nat Struct Biol, 10:713-7, Sept. 1, 2003.

9. D. Deamer et al., "The first cell membranes," Astrobiology, 2:371-81, 2002.

File Date: 12.01.03

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