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The Miller Experiment

July 30, 2014

Every scientist is familiar with the chemical compound, urea ((NH2)2CO), although not usually in a laboratory setting. One notable exception from my undergraduate days was a white-haired physiology professor who was seen by a student to be urinating in a laboratory sink. Perhaps "lab alcohol" was involved. I once used urea as an additive to an electroplating solution.

Urea was first synthesized from inorganic reagents by Friedrich Wöhler in 1828. He reacted silver cyanate (AgNCO) with ammonium chloride (NH4Cl), as follows:
AgNCO + NH4Cl -> (NH2)2CO + AgCl
In Wöhler's time, it was thought that living things and their chemical products were fundamentally different from ordinary chemicals. Wöhler's synthesis of urea showed that this concept of vitalism was wrong. This was the beginning of organic chemistry, which has subsequently given us useful materials from paint to pharmaceuticals.

Wöhler's synthesis of urea was also an entrée to the idea of abiogenesis, how life on Earth could arise from non-living matter. At some point in the history of the Earth, self-replicating, living matter appeared in Darwin's "warm little pond,"[1] and it eventually took over its entire surface. I wrote about abiogenesis and the idea of life on other planets in an earlier article (Catalytic Abiogenesis, January 26, 2011).

At first thought, the whole process of abiogenesis seems too improbable to have happened; but, then, where have all the organisms come from? Theory is one thing, but scientists are skeptical, and that's why they do experiments. In 1953, Stanley Miller, who was a Ph.D. student in chemistry under Nobelist, Harold Urey at the University of Chicago, performed an interesting experiment.

Stanley MillerStanley Miller in 1999 with a recreation of his 1953 abiogenesis experiment.

The spark device shown was once common in laboratories for checking glass assemblies for vacuum leaks.

Tens of thousands of volts are generated by a Tesla coil circuit, and any leaks would appear as a spot of light caused by excitation of gas molecules.

(NASA photo by James A. Sugar, via Wikimedia Commons.)

Miller put the supposed components of Earth's early reducing atmosphere, ammonia, methane, hydrogen and water, in a closed reaction vessel, as shown in the figure. He excited this mixture with artificial lightning produced by a laboratory device capable of producing high voltage electrical discharges. The reaction produced amino acids, an essential building block for living organisms.

Stanley Miller ExperimentSchematic diagram of Stanley Miller's 1953 abiogenesis experiment.

by Ned Shaw,
Indiana University

As critics of science enjoy pointing out, scientific theory is changeable. Wait long enough, and your coffee (or red wine, or a variety of other foods), once thought to be bad for your health, will become a health food. Research after Miller's experiment indicates that Earth's early atmosphere was different from Miller's mixture. Instead of ammonia, methane, hydrogen and water, it was more like carbon dioxide, carbon monoxide, nitrogen, and water. Some hydrogen and methane would have come from volcanic sources, as would lightning.

Miller's experiment got a "reboot" in 2008 when a graduate student discovered sealed glass vials containing samples from Miller's original experiments. NASA, which has invested heavily in astrobiology now that extrasolar planets are being discovered by the hundreds, funded a reanalysis of the reaction products with today's more sensitive equipment. One unplublished reaction simulated conditions near erupting volcanoes, and the reaction products were found by modern equipment to have produced twenty two amino acids.[2]

Data mining of Miller's samples and notebooks has produced some new avenues for investigation. Miller added cyanamide to his reactions, but he never analyzed the products. Cyanamide is a potential polymerization agent for amino acids, linking them into the the simple peptides from proteins and enzymes, necessary for life's biochemistry, are built. A research team from the Georgia Institute of Technology (Atlanta, Georgia), the NASA Johnson Space Center (Houston, Texas), the NASA Goddard Space Flight Center (Greenbelt, Maryland), The Scripps Research Institute (La Jolla, California), and the University of California (San Diego, California), has been doing a follow-up study of prebiotic cyanamide reactions.[3-4]

Stanley Miller's cyanamide samplesStanley Miller's cyanamide samples from 1958.

(Scripps Institution of Oceanography, UC San Diego image.)[4]

Miller's reason for adding cyanamide is unknown, although it's speculated that one of his coffee colleagues may have suggested it.[4] It's well known that random conversations among scientists from different backgrounds at universities and large corporate research laboratories have led to some interesting scientific advances. In Miller's time the chemical consensus was that reactions with cyanamide were only possible in an acidic environment, which would have been rare on the early Earth.[4]

Jeffrey Bada, who was Stanley Miller's second graduate student and a frequent collaborator in later years, was given boxes of Miller's samples in 1999. One box was labeled. "electric discharge sample," in Miller's own handwriting. Says Bada,
"I opened it up and inside were all these other little boxes... I started looking at them, and realized they were from all his original experiments; the ones he did in 1953 that he wrote the famous paper in Science on, plus a whole assortment of others related to that. It's something that should rightfully end up in the Smithsonian."[4]
Fortunately, from a scientific standpoint, these samples were marked with page number references to Miller's notebooks. These samples were from Miller's electrical discharge experiments with cyanamide while he was at the College of Physicians and Surgeons of Columbia University in 1958.[4]

These reaction samples from 1958 were analyzed using liquid chromatography, ion mobility spectrometry, and mass spectrometry, and they were found to contain peptides.[3-4] The analysis detected a dozen amino acids, 10 glycine-containing dipeptides, and 3 glycine-containing diketopiperazines.[3]

Since replication of experiments is an important part of science, the research team repeated Miller's cyanamide experiments, albeit with modern versions of the components, and observed similar products, including peptides.[3-4] Other experiments indicated that Strecker amino-acid synthesis, a series of chemical reactions by which amino acids are formed from aldehydes or ketones, plays an important role in such prebiotic synthesis.[3]

The research team acknowledged the assistance of the archivists of the Mandeville Special Collections at the Geisel Library of the University of California, San Diego, in producing Miller's original laboratory notebooks.[3] I wonder whether my former employer would be able to do the same with my many notebooks; or, if that would really matter. This research received support from the National Science Foundation and the NASA Astrobiology Program.[3-4]


  1. As quoted by Darwin's son, Francis, in The life and letters of Charles Darwin, 1887,
    "...my father wrote in 1871: "It is often said that all the conditions for the first production of a living organism are now present, which could ever have been present. But if (and oh! what a big if!) we could conceive in some warm little pond, with all sorts of ammonia and phosphoric salts, light, heat, electricity, &c., present, that a proteine compound was chemically formed ready to undergo stillmore complex changes, at the present day such matter would be instantly devoured or absorbed, which would not have been the case before living creatures were formed."
  2. David Bricker, Annie Reisewitz, Daniella Scalice, Nancy Neal-Jones and Bill Steigerwald, "Volcanoes May Have Provided Sparks and Chemistry for First Life," NASA Goddard Space Flight Center, October 16, 2008.
  3. Eric T. Parker, Dr. Manshui Zhou, Dr. Aaron S. Burton, Dr. Daniel P. Glavin, Dr. Jason P. Dworkin, Prof. Dr. Ramanarayanan Krishnamurthy, Prof. Dr. Facundo M. Fern´ndez, and Prof. Dr. Jeffrey L. Bada, "Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth," Angew. Chem. Int. Ed., Early View (June 25, 2014). doi: 10.1002/anie.201403683.
  4. Brett Israel, "Stanley Miller's Forgotten Experiments, Analyzed," Georgia Institute of Technology Press Release, June 25, 2014.

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