I can't remember how old I was when I learned about the Miller-Urey experiment—the abiotic synthesis of amino acids from sparking or irradiating gas mixtures containing ammonia, methane, water, and other gases that were thought to be present in the atmosphere of the primordial Earth—but I was pretty young. I may have learned it from Carl Sagan's Cosmos, which features a Cornell scientist carrying out the experiment, accompanied by dramatic music and clouds of liquid-nitrogen fog billowing around him. Some years later, from the pages of Scientific American magazine and a famous column called "The Amateur Science" (many years dead now), I learned about a curious set of experiments headed up by the chemist Sidney W. Fox, a Caltech Ph.D. who once worked with Caltech legend Linus Pauling. Fox addressed himself to the big unanswered question that's implied by the results of the Miller-Urey experiment: OK, so you can make a soup of amino acids and other biomolecules, but what then? How does one get from a solution of organic monomers to a self-contained lifeform?
There's a major physical hurdle: the condensation of two amino acids in aqueous solution to form an amine bond or "peptide bond" between the α-amino group of one amino acid and the carboxyl group of another, freeing a water molecule in the process, is not thermodynamically favorable under expected conditions. In the laboratory, condensing agents are used to form peptide bonds: these are compounds that react with the carboxyl group of an amino acid to produce a reactive intermediate which condenses with the amino group of a second amino acid. Carbodiimides, for example, organic reagents of the form RN=C=NR, react with an amino acid R'-CH(NH₂)-(C=O)OH to form an aminoacylated isourea R'-CH(NH₂)-(C=O)OC(NHR)=NR which then condenses with the second amino acid to form the amide bond, releasing the urea (RNH)₂C=O in the process. The carbodiimide acts like a dehydrating agent in other words, carrying away the water from the condensation of the peptide bond via the overall reaction RN=C=NR + H₂O → (RNH)₂C=O. There's a wide range of condensing agents in laboratory use for condensing amino acids into peptides—but how on Earth did it happen naturally? This is one of the great unsolved problems in the origin of organic life, and many possible answers have been proposed.
Sidney Fox worked on the simplest possible answer: thermal dehydration. He and his colleague Harada Kaoru, in 1958, found that if mixtures of amino acids were heated well above the boiling point of water in the presence of excess glutamic acid, they would condense into polymeric macromolecules which he dubbed "proteinoids". Thermal dehydration of glutamic acid yields a cyclic lactam, "pyroglutamic acid" or 2-pyrrolidone-5-carboxylic acid, which seems to serve both as a solvent and condensing agent for further reactions between amino acids. Fox suggested that volcanism perhaps yielded conditions under which amino acid mixtures could be dehydrated in this manner. The resulting proteinoids are like a brown amorphous goo that, when dispersed in electrolyte solutions, can easily be induced to self-organize into tiny microspheres about 1-5 microns in diameter. They could be observed to divide through budding, and Fox and his coworkers discovered they exhibited weak catalytic activity—hence Fox postulated that he'd in fact successfully created "protocells", the forerunners of Earth's living cells. "The Amateur Scientist" article in which I first learned about these remarkable experiments showed how easily an amateur worker could make Fox's proteinoid microspheres on their own.
So, good, right? Fox never stopped working on his proteinoids, from what I can see; he published papers about them through the 1980s. But his contention that he'd successfully made a protocell hasn't ever been fully accepted. His proteinoids contain peptide bonds but they're not true proteins; the harsh conditions of their synthesis cause numerous side reactions between amino acids. There's also the inconvenient fact that all the cells we know are contained not by protein (or proteinoid) vesicles but rather by lipid bilayers. So how could Fox's microspheres be the forerunner of modern cells?
All the same, the experiment is highly suggestive, and it definitely sounds like a fun thing to try some time. :=D
~Alyx Woodward