A half century after Stanley Miller redefined biochemistry with one of the most famous experiments in history, scientists are digging back into his archives and finding that Miller discovered even more than everyone assumed, himself included.
In 1953, as a graduate student at the University of Chicago, Miller filled a series of interconnected glass bulbs with gases like ammonia, hydrogen, and methane. He then boiled water inside the apparatus, shot some sparks through it, and collected the residues after the gases reacted. The combination of heat and electrical energy fused the methane, water, hydrogen, and ammonia into many organic compounds, including amino acids, the building blocks of proteins.
The experiment (reenacted at left by Jeffrey Bada, Miller's former student) demonstrated that the molecules necessary to build life were easy to assemble, and it also suggested that lightning and thunderstorms on the primitive earth might have created life, or at least proto-life, all by themselves. Miller’s experiment has been included in pretty much every biology textbook ever published since then.
Few people knew that Miller had actually run three different experiments with three different setups and only reported one of them in 1953. But after Miller’s death in 2007 from the complications of a stroke, his former students began digging through his old files in cardboard boxes, where they discovered fifty-six-year-old samples Miller had never mentioned.
“We determined we had portions of the solution from each of his three apparatuses that he tested,” said Jeffrey Bada, Miller’s second-ever graduate student and longtime friend, now a chemist himself at the University of California at San Diego. “I was dumbstruck by this.”
Bada decided to reinvestigate Miller’s experiments and co-authored a recent paper in Nature on the work. (The lead author on the paper was Adam Johnson, a student Bada supervised; three other scientists helped out.) Excitingly, Bada said, the samples he discovered were far richer in organic molecules than Miller had realized, which suggested a need to reinterpret the story of life on earth.
In the classic Miller experiment, water percolated into the spark chamber from above, slowly condensing near the electrodes. In a second experiment (left), steam was injected into the sparks from below at high speeds, like a jet of water. Though it may not have been Miller’s intention, Bada says, this second setup nicely mimics a volcano shooting steam and other gases into lightning. (On the diagram, (1) Boiled water shoots through a narrow opening into a bulb with reactive gases. (2) There, electrodes produce sparks. (3) A condenser turns steam into liquid water, which (4) collects in the trap.)
When Bada and Johnson analyzed the results of that second experiment with modern techniques and equipment, they found Miller had produced a far higher number of organic molecules than he assumed, including ten more amino acids than reported in 1953. He likely missed them because the analytical tools available then were millions of times less sensitive than those used now.
Bada added that Miller’s unreported experiments are important not only for their historical value but because they answer a major criticism of the original, reported experiment. The earth’s early atmosphere likely contained very little ammonia, hydrogen, or methane, which are reactive gases. Instead, it contained mostly nitrogen and carbon dioxide, which are nonreactive. Miller only included ammonia, hydrogen, and methane in his experiments.
However, “on the early earth, there were probably no continents,” Bada said, just many small volcanic islands (similar to Hawaii). “These volcanic islands had very deep roots, so the gases coming out of there would have been primitive gases like methane, ammonia, and hydrogen.” That explains their availability for reactions.
Plus, Bada added, even today, volcanic eruptions tend to attract lightning storms. Altogether, Miller’s “volcanic” apparatus seems to have been the most realistic of the three original experiments, and it was the setup that yielded the richest broth of organic molecules.
The third experiment, unfortunately, was a dud—Miller had used a different type of electrode, and very little happened biochemically. However, Bada still thinks there’s a lot to learn from Miller’s overall work. He and Johnson have investigated only a dozen of the nearly two hundred vials in Miller’s cardboard boxes.
With modern techniques, Bada says, “We can do a much better job characterizing what is in these samples. It will take us more than a year to sort through them all.”
Sam Kean is associate editor of Search.

