Miller–Urey experiment

The Miller–Urey experiment, or Miller experiment, was an experiment in chemical synthesis carried out in 1952 that simulated the conditions thought at the time to be present in the atmosphere of the early, prebiotic Earth. It is seen as one of the first successful experiments demonstrating the synthesis of organic compounds from inorganic constituents in an origin of life scenario. The experiment used methane, ammonia, hydrogen, in ratio 2:2:1, and water. Applying an electric arc resulted in the production of amino acids.
It is regarded as a groundbreaking experiment, and the classic experiment investigating the origin of life. It was performed in 1952 by Stanley Miller, supervised by Nobel laureate Harold Urey at the University of Chicago, and published the following year. At the time, it supported Alexander Oparin's and J. B. S. Haldane's hypothesis that the conditions on the primitive Earth favored chemical reactions that synthesized complex organic compounds from simpler inorganic precursors.
After Miller's death in 2007, scientists examining sealed vials preserved from the original experiments showed that more amino acids were produced in the original experiment than Miller reported with paper chromatography. While evidence suggests that Earth's prebiotic atmosphere might have typically had a composition different from the gas used in the Miller experiment, prebiotic experiments continue to produce racemic mixtures of simple-to-complex organic compounds, including amino acids, under varying conditions. Moreover, researchers have shown that transient, hydrogen-rich atmospheres – conducive to Miller–Urey synthesis – would have occurred after large asteroid impacts on early Earth.

History

Foundations of organic synthesis and the origin of life

Until the 19th century, there was considerable acceptance of the theory of spontaneous generation, the idea that "lower" animals, such as insects or rodents, arose from decaying matter. However, several experiments in the 19th century – particularly Louis Pasteur's swan neck flask experiment in 1859 — disproved the theory that life arose from decaying matter. Charles Darwin published On the Origin of Species that same year, describing the mechanism of biological evolution. While Darwin never publicly wrote about the first organism in his theory of evolution, in a letter to Joseph Dalton Hooker, he speculated:

But if we could conceive in some warm little pond with all sorts of ammonia and phosphoric salts, light, heat, electricity etcetera present, that a protein compound was chemically formed, ready to undergo still more complex changes "

At this point, it was known that organic molecules could be formed from inorganic starting materials, as Friedrich Wöhler had described the Wöhler synthesis of urea from ammonium cyanate in 1828. Several other early seminal works in the field of organic synthesis followed, including Alexander Butlerov's synthesis of sugars from formaldehyde and Adolph Strecker's synthesis of the amino acid alanine from acetaldehyde, ammonia, and hydrogen cyanide. In 1913, Walther Löb synthesized amino acids by exposing formamide to silent electric discharge, so scientists were beginning to produce the building blocks of life from simpler molecules, but these were not intended to simulate any prebiotic scheme or even considered relevant to origin of life questions.
But the scientific literature of the early 20th century contained speculations on the origin of life. In 1903, physicist Svante Arrhenius hypothesized that the first microscopic forms of life, driven by the radiation pressure of stars, could have arrived on Earth from space in the panspermia hypothesis. In the 1920s, Leonard Troland wrote about a primordial enzyme that could have formed by chance in the primitive ocean and catalyzed reactions, and Hermann J. Muller suggested that the formation of a gene with catalytic and autoreplicative properties could have set evolution in motion. Around the same time, Alexander Oparin's and J. B. S. Haldane's "Primordial soup" ideas were emerging, which hypothesized that a chemically-reducing atmosphere on early Earth would have been conducive to organic synthesis in the presence of sunlight or lightning, gradually concentrating the ocean with random organic molecules until life emerged. In this way, frameworks for the origin of life were coming together, but at the mid-20th century, hypotheses lacked direct experimental evidence.

Stanley Miller and Harold Urey

At the time of the Miller–Urey experiment, Harold Urey was a Professor of Chemistry at the University of Chicago who had a well-renowned career, including receiving the Nobel Prize in Chemistry in 1934 for his isolation of deuterium and leading efforts to use gaseous diffusion for uranium isotope enrichment in support of the Manhattan Project. In 1952, Urey postulated that the high temperatures and energies associated with large impacts in Earth's early history would have provided an atmosphere of methane, water, ammonia, and hydrogen, creating the reducing environment necessary for the Oparin-Haldane "primordial soup" scenario.
Stanley Miller arrived at the University of Chicago in 1951 to pursue a PhD under nuclear physicist Edward Teller, another prominent figure in the Manhattan Project. Miller began to work on how different chemical elements were formed in the early universe, but, after a year of minimal progress, Teller was to leave for California to establish Lawrence Livermore National Laboratory and further nuclear weapons research. Miller, having seen Urey lecture on his 1952 paper, approached him about the possibility of a prebiotic synthesis experiment. While Urey initially discouraged Miller, he agreed to allow Miller to try for a year. By February 1953, Miller had mailed a manuscript as sole author reporting the results of his experiment to Science. Urey refused to be listed on the manuscript because he believed his status would cause others to underappreciate Miller's role in designing and conducting the experiment and so encouraged Miller to take full credit for the work. Despite this the set-up is still most commonly referred to including both their names. After not hearing from Science for a few weeks, a furious Urey wrote to the editorial board demanding an answer, stating, "If Science does not wish to publish this promptly we will send it to the Journal of the American Chemical Society." Miller's manuscript was eventually published in Science in May 1953.

Experiment

In the original 1952 experiment, methane, ammonia, and hydrogen were all sealed together in a 2:2:1 ratio inside a sterile 5-L glass flask connected to a 500-mL flask half-full of water. The gas chamber was intended to represent Earth's prebiotic atmosphere, while the water simulated an ocean. The water in the smaller flask was boiled such that water vapor entered the gas chamber and mixed with the "atmosphere". A continuous electrical spark was discharged between a pair of electrodes in the larger flask. The spark passed through the mixture of gases and water vapor, simulating lightning. A condenser below the gas chamber allowed aqueous solution to accumulate into a U-shaped trap at the bottom of the apparatus, which was sampled.
After a day, the solution that had collected at the trap was pink, and after a week of continuous operation the solution was deep red and turbid, which Miller attributed to organic matter absorbed onto colloidal silica. The boiling flask was then removed, and mercuric chloride was added to prevent microbial contamination. The reaction was stopped by adding barium hydroxide and sulfuric acid, and evaporated to remove impurities. Using paper chromatography, Miller identified five amino acids present in the solution: glycine, α-alanine and β-alanine were positively identified, while aspartic acid and α-aminobutyric acid were less certain, due to the spots being faint.
Materials and samples from the original experiments remained in 2017 under the care of Miller's former student, Jeffrey Bada, a professor at the UCSD, Scripps Institution of Oceanography who also conducts origin of life research., the apparatus used to conduct the experiment was on display at the Denver Museum of Nature and Science.

Chemistry of experiment

In 1957 Miller published research describing the chemical processes occurring inside his experiment. Hydrogen cyanide and aldehydes were demonstrated to form as intermediates early on in the experiment due to the electric discharge. This agrees with current understanding of atmospheric chemistry, as HCN can generally be produced from reactive radical species in the atmosphere that arise when CH₄ and nitrogen break apart under ultraviolet light. Similarly, aldehydes can be generated in the atmosphere from radicals resulting from CH₄ and H₂O decomposition and other intermediates like methanol. Several energy sources in planetary atmospheres can induce these dissociation reactions and subsequent hydrogen cyanide or aldehyde formation, including lightning, ultraviolet light, and galactic cosmic rays.
For example, here is a set photochemical reactions of species in the Miller–Urey atmosphere that can result in formaldehyde:
File:Evidence for Strecker-type amino acid synthesis in the Miller-Urey experiment.webp|thumb|392x392px|A) Cyanohydrin and Strecker Concentrations of ammonia, aldehydes, hydrogen cyanide, and amino acids during a Miller–Urey experiment, reproduced from Miller by Cleaves. The concentrations of aldehydes and hydrogen cyanide during amino acid production in aqueous solution provided strong evidence that Strecker synthesis occurs in Miller–Urey chemical environments. Production of hydroxy acids through the cyanohydrin scheme also likely occurs. From: Cleaves, H.J. Prebiotic Chemistry: What We Know, What We Don't. Evo Edu Outreach 5, 342–360. Licensed under CC-BY 2.0.
A photochemical path to HCN from NH₃ and CH₄ is:
Other active intermediate compounds have been detected in the aqueous solution of Miller–Urey-type experiments, but the immediate HCN and aldehyde production, the production of amino acids accompanying the plateau in HCN and aldehyde concentrations, and slowing of amino acid production rate during HCN and aldehyde depletion provided strong evidence that Strecker amino acid synthesis was occurring in the aqueous solution.
Strecker synthesis describes the reaction of an aldehyde, ammonia, and HCN to a simple amino acid through an aminoacetonitrile intermediate:
Furthermore, water and formaldehyde can react via Butlerov's reaction to produce various sugars like ribose.
The experiments showed that simple organic compounds, including the building blocks of proteins and other macromolecules, can abiotically be formed from gases with the addition of energy.