Miller–Urey experiment

{{Short description|Experiment testing the origin of life}} {{Use mdy dates|date=October 2024}} thumb|upright=1.6|The Miller–Urey experiment was a synthesis of small organic molecules in a mixture of simple gases in a thermal gradient created by heating (right) and cooling (left) the mixture at the same time, with electrical discharges.

The '''Miller–Urey experiment''',<ref>{{cite journal |vauthors=Hill HG, Nuth JA |year=2003 |title=The catalytic potential of cosmic dust: implications for prebiotic chemistry in the solar nebula and other protoplanetary systems |url=https://www.liebertpub.com/doi/10.1089/153110703769016389 |journal=Astrobiology |volume=3 |issue=2 |pages=291–304 |bibcode=2003AsBio...3..291H |doi=10.1089/153110703769016389 |pmid=14577878 |url-access=subscription}}</ref> or '''Miller experiment''',<ref>{{cite journal |author1=Balm SP |author2=Hare J.P. |author3=Kroto HW |year=1991 |title=The analysis of comet mass spectrometric data |journal=Space Science Reviews |volume=56 |issue=1–2 |pages=185–9 |bibcode=1991SSRv...56..185B |doi=10.1007/BF00178408 |s2cid=123124418}}</ref> 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 (CH₄), ammonia (NH₃), hydrogen (H₂), in ratio 2:2:1,<ref name="miller19532"/> and water (H₂O). Applying an electric arc (simulating lightning) resulted in the production of amino acids.

It is regarded as a groundbreaking experiment, and the classic experiment investigating the origin of life (abiogenesis). 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.<ref name="miller19532">{{cite journal |last=Miller |first=Stanley L. |year=1953 |title=Production of Amino Acids Under Possible Primitive Earth Conditions |journal=Science |volume=117 |issue=3046 |pages=528–9 |bibcode=1953Sci...117..528M |pmid=13056598 |doi=10.1126/science.117.3046.528 |url=https://abenteuer-universum.de/pdf/miller_1953.pdf |access-date=2011-01-17 |url-status=live |archive-url=https://web.archive.org/web/20120317062622/http://www.abenteuer-universum.de/pdf/miller_1953.pdf |archive-date=2012-03-17}}</ref><ref>{{cite journal |last=Miller |first=Stanley L. |author2=Harold C. Urey |year=1959 |title=Organic Compound Synthesis on the Primitive Earth |journal=Science |volume=130 |issue=3370 |pages=245–51 |bibcode=1959Sci...130..245M |doi=10.1126/science.130.3370.245 |pmid=13668555}} Miller states that he made "A more complete analysis of the products" in the 1953 experiment, listing additional results.</ref><ref>{{cite journal |author1=A. Lazcano |author2=J. L. Bada |year=2004 |title=The 1953 Stanley L. Miller Experiment: Fifty Years of Prebiotic Organic Chemistry |journal=Origins of Life and Evolution of Biospheres |volume=33 |issue=3 |pages=235–242 |bibcode=2003OLEB...33..235L |doi=10.1023/A:1024807125069 |pmid=14515862 |s2cid=19515024}}</ref>

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.<ref name="BBC2">{{cite web |date=26 August 2009 |title=The Spark of Life |url=http://www.bbc.co.uk/programmes/b00mbvfh |url-status=live |archive-url=https://web.archive.org/web/20101113011054/http://www.bbc.co.uk/programmes/b00mbvfh |archive-date=2010-11-13 |website=BBC Four |postscript=. TV Documentary.}}</ref> 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.<ref name="bada20132">{{cite journal<!-- Citation bot bypass--> |last1=Bada |first1=Jeffrey L. |year=2013 |title=New insights into prebiotic chemistry from Stanley Miller's spark discharge experiments |journal=Chemical Society Reviews |volume=42 |issue=5 |pages=2186–96 |doi=10.1039/c3cs35433d |pmid=23340907 |s2cid=12230177 |url=https://www.semanticscholar.org/paper/New-insights-into-prebiotic-chemistry-from-Stanley-Bada/ee5b3b10e890dc36f2d67a206471924e78b4813e}}</ref> Moreover, researchers have shown that transient, hydrogen-rich atmospheres – conducive to Miller–Urey synthesis – would have occurred after large asteroid impacts on early Earth.<ref name="Zahnle-2020">{{Cite journal |last1=Zahnle |first1=Kevin J. |last2=Lupu |first2=Roxana |last3=Catling |first3=David C. |last4=Wogan |first4=Nick |date=2020-05-01 |title=Creation and Evolution of Impact-generated Reduced Atmospheres of Early Earth |journal=The Planetary Science Journal |language=en |volume=1 |issue=1 |page=11 |doi=10.3847/PSJ/ab7e2c |arxiv=2001.00095 |bibcode=2020PSJ.....1...11Z |issn=2632-3338 |doi-access=free}}</ref><ref name="Wogan-2023">{{Cite journal |last1=Wogan |first1=Nicholas F. |last2=Catling |first2=David C. |last3=Zahnle |first3=Kevin J. |last4=Lupu |first4=Roxana |date=2023-09-01 |title=Origin-of-life Molecules in the Atmosphere after Big Impacts on the Early Earth |journal=The Planetary Science Journal |volume=4 |issue=9 |page=169 |doi=10.3847/psj/aced83 |arxiv=2307.09761 |bibcode=2023PSJ.....4..169W |issn=2632-3338 |doi-access=free}}</ref>

==History==

===Foundations of organic synthesis and the origin of life=== {{See also|History of research into 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.<ref>{{Cite book |last=Sheldon |first=Robert B. |title=Astrobiology and Planetary Missions |date=2005-08-18 |editor-last=Hoover |editor-first=Richard B. |editor2-last=Levin |editor2-first=Gilbert V. |editor3-last=Rozanov |editor3-first=Alexei Y. |editor4-last=Gladstone |editor4-first=G. Randall |chapter=Historical development of the distinction between bio- and abiogenesis |volume=5906 |pages=444–456 |doi=10.1117/12.663480 |s2cid=44194609 |chapter-url=https://www.spiedigitallibrary.org/conference-proceedings-of-spie/5906/1/Historical-development-of-the-distinction-between-bio--and-abiogenesis/10.1117/12.663480.short}}</ref> However, several experiments in the 19th century – particularly Louis Pasteur's swan neck flask experiment in 1859<ref>{{Cite web |date=2022-05-27 |title=Pasteur's "col de cygnet" (1859) {{!}} British Society for Immunology |url=https://www.immunology.org/pasteurs-col-de-cygnet-1859 |access-date=2023-11-11 |archive-url=https://web.archive.org/web/20220527024603/https://www.immunology.org/pasteurs-col-de-cygnet-1859 |archive-date=2022-05-27}}</ref> — 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.<ref>{{Cite book |last=Darwin |first=Charles |title=On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life |publisher=John Murray |year=1859 |location=London}}</ref> While Darwin never publicly wrote about the first organism in his theory of evolution, in a letter to Joseph Dalton Hooker, he speculated:<blockquote>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 etcetera present, that a protein compound was chemically formed, ready to undergo still more complex changes [...]"<ref>Darwin, Charles. Darwin Correspondence Project, "Letter No. 7471", 1871. Available online: https://www.darwinproject.ac.uk/letter?docId=letters/DCP-LETT-7471.xml</ref></blockquote> left|thumb|258x258px|Portrait photograph of Alexander Oparin

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.<ref>Friedrich Wöhler (1828). "Ueber künstliche Bildung des Harnstoffs". Annalen der Physik und Chemie. 88 (2): 253–256</ref> 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.<ref name="Miller">Miller, S. L., & Cleaves, H. J. (2006). Prebiotic chemistry on the primitive Earth. ''Systems biology'', ''1'', 1.</ref> In 1913, Walther Löb synthesized amino acids by exposing formamide to silent electric discharge,<ref>Löb, W. (1913). Über das Verhalten des Formamids unter der Wirkung der stillen Entladung Ein Beitrag zur Frage der Stickstoff'''''‐'''''Assimilation. ''Berichte der deutschen chemischen Gesellschaft'', ''46''(1), 684–697.</ref> 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.<ref name="Miller"/>

But the scientific literature of the early 20th century contained speculations on the origin of life.<ref name="Miller"/><ref>{{Cite book |title=Life's origin: the beginnings of biological evolution |date=2002 |publisher=Univ. of California Press |isbn=978-0-520-23391-1 |editor-last=Schopf |editor-first=J. William |location=Berkeley, Calif.}}</ref> 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.<ref>Arrhenius, Svante (1903). "Die Verbreitung des Lebens im Weltenraum" [The Distribution of Life in Space]. ''Die Umschau.''</ref> 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.<ref>{{Cite journal |last=Lazcano |first=A. |date=2010-11-01 |title=Historical Development of Origins Research |journal=Cold Spring Harbor Perspectives in Biology |language=en |volume=2 |issue=11 |article-number=a002089 |doi=10.1101/cshperspect.a002089 |issn=1943-0264 |pmc=2964185 |pmid=20534710 |bibcode=2010CSHPB...202089L }}</ref> 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.<ref>{{Citation |last1=Kumar |first1=Dhavendra |title=Cosmic Genetic Evolution |date=2020 |series=Advances in Genetics |volume=106 |pages=xv–xviii |publisher=Elsevier |language=en |doi=10.1016/s0065-2660(20)30037-7 |isbn=978-0-12-821518-0 |pmc=7568464 |pmid=33081930 |last2=Steele |first2=Edward J. |last3=Wickramasinghe |first3=N. Chandra|chapter=Preface: The origin of life and astrobiology}}</ref> 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 === thumb|Stanley Miller in 1999, posed with an apparatus like that used in the original experiment 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<ref>Harold C. Urey – Biographical. NobelPrize.org. Nobel Prize Outreach AB 2023. Mon. 13 Nov 2023. https://www.nobelprize.org/prizes/chemistry/1934/urey/biographical/</ref> and leading efforts to use gaseous diffusion for uranium isotope enrichment in support of the Manhattan Project.<ref>{{Cite web |title=Harold C. Urey |url=https://www.nndb.com/people/873/000092597/ |access-date=2023-11-13 |website=nndb.com}}</ref> 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 (CH₄), water (H₂O), ammonia (NH₃), and hydrogen (H₂), creating the reducing environment necessary for the Oparin-Haldane "primordial soup" scenario.<ref name="Urey-1952">{{Cite journal |last=Urey |first=Harold C. |date=April 1, 1952 |title=On the Early Chemical History of the Earth and the Origin of Life |journal=Proceedings of the National Academy of Sciences |volume=38 |issue=4 |pages=351–363 |doi=10.1073/pnas.38.4.351 |pmid=16589104 |bibcode=1952PNAS...38..351U |doi-access=free |pmc=1063561}}</ref>

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.<ref name="Lazcano-2008">{{Cite journal |last1=Lazcano |first1=Antonio |last2=Bada |first2=Jeffrey L. |date=2008-10-01 |title=Stanley L. Miller (1930–2007): Reflections and Remembrances |journal=Origins of Life and Evolution of Biospheres |language=en |volume=38 |issue=5 |pages=373–381 |doi=10.1007/s11084-008-9145-2 |pmid=18726708 |bibcode=2008OLEB...38..373L |s2cid=1167340 |issn=1573-0875}}</ref> 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.<ref name="Lazcano-2008"/> 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.<ref name="Lazcano-2008"/> By February 1953, Miller had mailed a manuscript as sole author reporting the results of his experiment to ''Science.''<ref name="Lazcano-2003">{{Cite journal |last1=Lazcano |first1=Antonio |last2=Bada |first2=Jeffrey L. |date=2003-06-01 |title=The 1953 Stanley L. Miller Experiment: Fifty Years of Prebiotic Organic Chemistry |journal=Origins of Life and Evolution of the Biosphere |language=en |volume=33 |issue=3 |pages=235–242 |doi=10.1023/A:1024807125069 |pmid=14515862 |bibcode=2003OLEB...33..235L |issn=1573-0875}}</ref> 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.<ref name="Lazcano-2003"/><ref>{{cite magazine |last=Marshall |first=Michael |date=2023-11-06 |title=The elusive origins of life |magazine=New Scientist Magazine |location=Australia |publisher=New Scientist}}</ref> 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''."<ref name="Lazcano-2003"/> Miller's manuscript was eventually published in ''Science'' in May 1953.<ref name="Lazcano-2003"/>

== Experiment == thumb|Descriptive video of the experiment In the original 1952 experiment, methane (CH₄), ammonia (NH₃), and hydrogen (H₂) were all sealed together in a 2:2:1 ratio (1 part H₂) inside a sterile 5-L glass flask connected to a 500-mL flask half-full of water (H₂O). 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.<ref name="miller19532"/> The boiling flask was then removed, and mercuric chloride (a poison) 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 (AABA) were less certain, due to the spots being faint.<ref name="miller19532"/>

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.<ref name="Dreifus-2010">{{cite news |last=Dreifus |first=Claudia |author-link=Claudia Dreifus |date=2010-05-17 |title=A Conversation With Jeffrey L. Bada: A Marine Chemist Studies How Life Began |newspaper=nytimes.com |url=https://www.nytimes.com/2010/05/18/science/18conv.html |url-status=live |archive-url=https://web.archive.org/web/20170118034218/http://www.nytimes.com/2010/05/18/science/18conv.html |archive-date=2017-01-18}}</ref> {{as of|2013}}, the apparatus used to conduct the experiment was on display at the Denver Museum of Nature and Science.<ref>{{cite news |title=Astrobiology Collection: Miller–Urey Apparatus |publisher=Denver Museum of Nature & Science |url=http://www.dmns.org/science/museum-scientists/david-grinspoon/funky-science-wonder-lab/research-updates/astrobiology-collection-miller-urey-apparatus |url-status=dead |archive-url=https://web.archive.org/web/20130524090309/http://www.dmns.org/science/museum-scientists/david-grinspoon/funky-science-wonder-lab/research-updates/astrobiology-collection-miller-urey-apparatus/ |archive-date=2013-05-24}}</ref>

==Chemistry of experiment== In 1957 Miller published research describing the chemical processes occurring inside his experiment.<ref name="Miller-1957">{{Cite journal |last=Miller |first=Stanley L. |date=1957-01-01 |title=The mechanism of synthesis of amino acids by electric discharges |journal=Biochimica et Biophysica Acta |volume=23 |issue=3 |pages=480–489 |doi=10.1016/0006-3002(57)90366-9 |pmid=13426157 |issn=0006-3002}}</ref> Hydrogen cyanide (HCN) and aldehydes (e.g., formaldehyde) were demonstrated to form as intermediates early on in the experiment due to the electric discharge.<ref name="Miller-1957"/> 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 (UV) light.<ref name="Sullivan-2007">{{Cite book |last1=Sullivan |first1=Woodruff Turner |title=Planets and life: the emerging science of astrobiology |last2=Baross |first2=John A. |date=2007 |publisher=Cambridge University Press |isbn=978-0-521-82421-7 |location=Cambridge}}</ref> Similarly, aldehydes can be generated in the atmosphere from radicals resulting from CH₄ and H₂O decomposition and other intermediates like methanol.<ref name="Ferris-1975">{{Cite journal |last1=Ferris |first1=J. P. |last2=Chen |first2=C. T. |date=1975 |title=Chemical evolution. XXVI. Photochemistry of methane, nitrogen, and water mixtures as a model for the atmosphere of the primitive earth |url=https://pubs.acs.org/doi/abs/10.1021/ja00844a007 |journal=Journal of the American Chemical Society |language=en |volume=97 |issue=11 |pages=2962–2967 |doi=10.1021/ja00844a007 |pmid=1133344 |bibcode=1975JAChS..97.2962F |issn=0002-7863 |url-access=subscription}}</ref> Several energy sources in planetary atmospheres can induce these dissociation reactions and subsequent hydrogen cyanide or aldehyde formation, including lightning,<ref>{{Cite journal |last1=Rimmer |first1=P. B. |last2=Helling |first2=Ch |date=2016-05-23 |title=A Chemical Kinetics Network for Lightning and Life in Planetary Atmospheres |journal=The Astrophysical Journal Supplement Series |volume=224 |issue=1 |page=9 |doi=10.3847/0067-0049/224/1/9 |arxiv=1510.07052 |bibcode=2016ApJS..224....9R |issn=1538-4365 |doi-access=free}}</ref> ultraviolet light,<ref name="Sullivan-2007"/> and galactic cosmic rays.<ref>{{Cite journal |last=Huntress |first=W. T. |date=1976 |title=The chemistry of planetary atmospheres |url=https://pubs.acs.org/doi/abs/10.1021/ed053p204 |journal=Journal of Chemical Education |language=en |volume=53 |issue=4 |page=204 |doi=10.1021/ed053p204 |bibcode=1976JChEd..53..204H |issn=0021-9584 |url-access=subscription}}</ref>

For example, here is a set photochemical reactions of species in the Miller–Urey atmosphere that can result in formaldehyde:<ref name="Ferris-1975"/>

: H₂O + ''hv'' → H + OH<ref>{{Cite journal |last1=Getoff |first1=N. |last2=Schenck |first2=G. O. |date=1968 |title=PRIMARY PRODUCTS OF LIQUID WATER PHOTOLYSIS AT 1236, 1470 AND 1849 Å |url=https://onlinelibrary.wiley.com/doi/10.1111/j.1751-1097.1968.tb05859.x |journal=Photochemistry and Photobiology |language=en |volume=8 |issue=3 |pages=167–178 |doi=10.1111/j.1751-1097.1968.tb05859.x |s2cid=97474816 |issn=0031-8655 |url-access=subscription}}</ref> : CH₄ + OH → CH₃ + HOH<ref>{{Cite journal |last=Wilson |first=Wm. E. |date=1972-04-01 |title=A Critical Review of the Gas-Phase Reaction Kinetics of the Hydroxyl Radical |journal=Journal of Physical and Chemical Reference Data |volume=1 |issue=2 |pages=535–573 |doi=10.1063/1.3253102 |bibcode=1972JPCRD...1..535W |issn=0047-2689}}</ref> : CH₃ + OH → CH₃OH<ref>{{Cite journal |last1=Greenberg |first1=Raymond I. |last2=Heicklen |first2=Julian |date=1972 |title=The reaction of O( 1 D ) with CH 4 |url=https://onlinelibrary.wiley.com/doi/10.1002/kin.550040406 |journal=International Journal of Chemical Kinetics |language=en |volume=4 |issue=4 |pages=417–432 |doi=10.1002/kin.550040406 |issn=0538-8066 |url-access=subscription}}</ref> : CH₃OH + ''hv'' → CH₂O (formaldehyde) + H₂<ref>{{Cite journal |last1=Hagege |first1=Janine |last2=Leach |first2=Sydney |last3=Vermeil |first3=Catherine |date=1965 |title=Photochimie du méthanol en phase vapeur A 1 236 et A 1 849 Å |url=https://jcp.edpsciences.org/articles/jcp/abs/1965/01/jcp196562p736/jcp196562p736.html |journal=Journal de Chimie Physique |language=fr |volume=62 |pages=736–746 |doi=10.1051/jcp/1965620736 |bibcode=1965JCP....62..736H |issn=0021-7689 |url-access=subscription}}</ref>

[[File:Evidence for Strecker-type amino acid synthesis in the Miller-Urey experiment.webp|thumb|392x392px|A) Cyanohydrin (top) and Strecker (bottom) schemes for synthesis of hydroxy acids and amino acids, respectively. B) Concentrations of ammonia, aldehydes, hydrogen cyanide, and amino acids during a Miller–Urey experiment, reproduced from Miller (1957)<ref name="Miller-1957"/> by Cleaves (2012).<ref>{{Cite journal |last=Cleaves |first=H. James |date=2012 |title=Prebiotic Chemistry: What We Know, What We Don't |journal=Evolution: Education and Outreach |language=en |volume=5 |issue=3 |pages=342–360 |doi=10.1007/s12052-012-0443-9 |issn=1936-6434 |doi-access=free}}</ref> 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 (2012). Licensed under CC-BY 2.0.]] A photochemical path to HCN from NH₃ and CH₄ is:<ref>{{Cite journal |last=Hu |first=Renyu |date=2021-11-01 |title=Photochemistry and Spectral Characterization of Temperate and Gas-rich Exoplanets |journal=The Astrophysical Journal |volume=921 |issue=1 |page=27 |doi=10.3847/1538-4357/ac1789 |arxiv=2108.04419 |bibcode=2021ApJ...921...27H |issn=0004-637X |doi-access=free}}</ref>

: NH₃ + ''hv'' → NH₂ + H : NH₂ + CH₄ → NH₃ + CH₃ : NH₂ + CH₃ → CH₅N : CH₅N + ''hv'' → HCN + 2H₂

Other active intermediate compounds (acetylene, cyanoacetylene, etc.) have been detected in the aqueous solution of Miller–Urey-type experiments,<ref>{{Cite journal |last=Orgel |first=Leslie E. |date=2004 |title=Prebiotic Adenine Revisited: Eutectics and Photochemistry |journal=Origins of Life and Evolution of the Biosphere |language=en |volume=34 |issue=4 |pages=361–369 |bibcode=2004OLEB...34..361O |doi=10.1023/B:ORIG.0000029882.52156.c2 |pmid=15279171 |s2cid=4998122}}</ref> 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.<ref name="Miller-1957"/>

Strecker synthesis describes the reaction of an aldehyde, ammonia, and HCN to a simple amino acid through an aminoacetonitrile intermediate:

: CH₂O + HCN + NH₃ → NH₂-CH₂-CN (aminoacetonitrile) + H₂O : NH₂-CH₂-CN + 2H₂O → NH₃ + NH₂-CH₂-COOH (glycine)

Furthermore, water and formaldehyde can react via Butlerov's reaction to produce various sugars like ribose.<ref>{{Cite journal |last=Mense |first=Thorben H. |date=December 2019 |title=A Closer Look at Reactions in the Miller–Urey-Experiment using Coupled Gas Chromatography – Mass Spectrometry |url=https://www2.physik.uni-bielefeld.de/fileadmin/user_upload/theory_e6/Master_Theses/MasterMiller1912.pdf |journal=Bielefeld University}}</ref>

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.

== Related experiments and follow-up work ==

=== Contemporary experiments === [[File:Huygens surface color enhanced.jpg|thumb|324x324px|The surface of Titan as viewed from the ''Huygens'' lander. Tholins, complex particles formed by UV irradiation on the N₂ and CH₄ atmosphere, are likely the source of the reddish haze.]] There were a few similar spark discharge experiments contemporaneous with Miller–Urey. An article in ''The New York Times'' (March 8, 1953) titled "Looking Back Two Billion Years" describes the work of Wollman M. MacNevin at Ohio State University, before the Miller Science paper was published in May 1953. MacNevin was passing 100,000V sparks through methane and water vapor and produced "resinous solids" that were "too complex for analysis."<ref name="Lazcano-2003"/><ref>{{cite book |author=Krehl, Peter O. K. |title=History of Shock Waves, Explosions and Impact: A Chronological and Biographical Reference |publisher=Springer-Verlag |year=2009 |page=603}}</ref><ref>{{cite news |title=Looking Back Two Billion Years |language=en |work=The New York Times |url=https://www.nytimes.com/1953/03/08/archives/looking-back-two-billion-years.html}}</ref> Furthermore, K. A. Wilde submitted a manuscript to ''Science'' on December 15, 1952, before Miller submitted his paper to the same journal in February 1953. Wilde's work, published on July 10, 1953, used voltages up to only 600V on a binary mixture of carbon dioxide (CO₂) and water in a flow system and did not note any significant reduction products.<ref>{{cite journal |last1=Wilde |first1=Kenneth A. |last2=Zwolinski |first2=Bruno J. |last3=Parlin |first3=Ransom B. |date=July 1953 |title=The Reaction Occurring in CO₂, ₂O Mixtures in a High-Frequency Electric Arc |journal=Science |volume=118 |issue=3054 |pages=43–44 |bibcode=1953Sci...118...43W |doi=10.1126/science.118.3054.43-a |pmid=13076175 |s2cid=11170339}}</ref> According to some, the reports of these experiments explain why Urey was rushing Miller's manuscript through ''Science'' and threatening to submit to the ''Journal of the American Chemical Society.''<ref name="Lazcano-2003"/>

By introducing an experimental framework to test prebiotic chemistry, the Miller–Urey experiment paved the way for future origin of life research.<ref>{{Cite book |last=James Cleaves II |first=H. |title=Prebiotic Chemistry and Life's Origin |chapter=The Miller–Urey Experiment's Impact on Modern Approaches to Prebiotic Chemistry |date=2022 |chapter-url=https://books.rsc.org/books/edited-volume/2003/chapter/4583571/The-Miller-Urey-Experiment-s-Impact-on-Modern |pages=165–176 |language=en |doi=10.1039/9781839164798-00165 |isbn=978-1-78801-749-7}}</ref> In 1961, Joan Oró produced milligrams of the nucleobase adenine from a concentrated solution of HCN and NH₃ in water.<ref>{{cite journal |vauthors=Oró J, Kimball AP |date=August 1961 |title=Synthesis of purines under possible primitive earth conditions. I. Adenine from hydrogen cyanide |journal=Archives of Biochemistry and Biophysics |volume=94 |issue=2 |pages=217–27 |doi=10.1016/0003-9861(61)90033-9 |pmid=13731263}}</ref> Oró found that several amino acids were also formed from HCN and ammonia under those conditions.<ref>{{cite journal |vauthors=Oró J, Kamat SS |date=April 1961 |title=Amino-acid synthesis from hydrogen cyanide under possible primitive earth conditions |journal=Nature |volume=190 |issue=4774 |pages=442–3 |bibcode=1961Natur.190..442O |doi=10.1038/190442a0 |pmid=13731262 |s2cid=4219284}}</ref> Experiments conducted later showed that the other RNA and DNA nucleobases could be obtained through simulated prebiotic chemistry with a reducing atmosphere.<ref>{{cite book |author=Oró J |title=Origins of Prebiological Systems and of Their Molecular Matrices |publisher=New York Academic Press |year=1967 |editor=Fox SW |page=137}}</ref><ref>{{Cite journal |last1=Ferus |first1=Martin |last2=Pietrucci |first2=Fabio |last3=Saitta |first3=Antonino Marco |last4=Knížek |first4=Antonín |last5=Kubelík |first5=Petr |last6=Ivanek |first6=Ondřej |last7=Shestivska |first7=Violetta |last8=Civiš |first8=Svatopluk |date=2017-04-25 |title=Formation of nucleobases in a Miller–Urey reducing atmosphere |journal=Proceedings of the National Academy of Sciences |language=en |volume=114 |issue=17 |pages=4306–4311 |doi=10.1073/pnas.1700010114 |issn=0027-8424 |pmc=5410828 |pmid=28396441 |bibcode=2017PNAS..114.4306F |doi-access=free}}</ref> Other researchers also began using UV-photolysis in prebiotic schemes, as the UV flux would have been much higher on early Earth.<ref>{{Cite journal |last1=Canuto |first1=V. M. |last2=Levine |first2=J. S. |last3=Augustsson |first3=T. R. |last4=Imhoff |first4=C. L. |date=1983-06-01 |title=Oxygen and ozone in the early Earth's atmosphere |journal=Precambrian Research |series=Development and interactions of the Precambrian atmosphere, lithosphere and biosphere: results and challenges |volume=20 |issue=2 |pages=109–120 |doi=10.1016/0301-9268(83)90068-2 |bibcode=1983PreR...20..109C |issn=0301-9268}}</ref> For example, UV-photolysis of water vapor with carbon monoxide was found to yield various alcohols, aldehydes, and organic acids.<ref>{{cite journal |last1=Bar-Nun |first1=Akiva |last2=Hartman |first2=Hyman |year=1978 |title=Synthesis of organic compounds from carbon monoxide and water by UV photolysis |journal=Origins of Life |volume=9 |issue=2 |pages=93–101 |bibcode=1978OrLi....9...93B |doi=10.1007/BF00931407 |pmid=752138 |s2cid=33972427}}</ref> In the 1970s, Carl Sagan used Miller–Urey-type reactions to synthesize and experiment with complex organic particles dubbed "tholins", which likely resemble particles formed in hazy atmospheres like that of Titan.<ref name="Sagan-1979">{{Cite journal |last1=Sagan |first1=Carl |last2=Khare |first2=B. N. |date=1979 |title=Tholins: organic chemistry of interstellar grains and gas |url=https://www.nature.com/articles/277102a0 |journal=Nature |language=en |volume=277 |issue=5692 |pages=102–107 |doi=10.1038/277102a0 |bibcode=1979Natur.277..102S |s2cid=4261076 |issn=1476-4687 |url-access=subscription}}</ref>

=== Modified Miller–Urey experiments === Much work has been done since the 1950s toward understanding how Miller–Urey chemistry behaves in various environmental settings. In 1983, testing different atmospheric compositions, Miller and another researcher repeated experiments with varying proportions of H₂, H₂O, N₂, CO₂ or CH₄, and sometimes NH₃.<ref name="Miller-1983">{{Cite journal |last1=Miller |first1=Stanley L. |last2=Schlesinger |first2=Gordon |date=1983-01-01 |title=The atmosphere of the primitive earth and the prebiotic synthesis of organic compounds |journal=Advances in Space Research |volume=3 |issue=9 |pages=47–53 |doi=10.1016/0273-1177(83)90040-6 |pmid=11542461 |bibcode=1983AdSpR...3i..47M |issn=0273-1177}}</ref> They found that the presence or absence of NH₃ in the mixture did not significantly impact amino acid yield, as NH₃ was generated from N₂ during the spark discharge.<ref name="Miller-1983"/> Additionally, CH₄ proved to be one of the most important atmospheric ingredients for high yields, likely due to its role in HCN formation.<ref name="Miller-1983"/> Much lower yields were obtained with more oxidized carbon species in place of CH₄, but similar yields could be reached with a high H₂/CO₂ ratio.<ref name="Miller-1983"/> Thus, Miller–Urey reactions work in atmospheres of other compositions as well, depending on the ratio of reducing and oxidizing gases. More recently, Jeffrey Bada and H. James Cleaves, graduate students of Miller, hypothesized that the production of nitrites, which destroy amino acids, in CO₂ and N₂-rich atmospheres may explain low amino acids yields.<ref name="Cleaves-2008">{{Cite journal |last1=Cleaves |first1=H. James |last2=Chalmers |first2=John H. |last3=Lazcano |first3=Antonio |last4=Miller |first4=Stanley L. |last5=Bada |first5=Jeffrey L. |date=2008 |title=A Reassessment of Prebiotic Organic Synthesis in Neutral Planetary Atmospheres |url=http://link.springer.com/10.1007/s11084-007-9120-3 |journal=Origins of Life and Evolution of Biospheres |language=en |volume=38 |issue=2 |pages=105–115 |doi=10.1007/s11084-007-9120-3 |pmid=18204914 |bibcode=2008OLEB...38..105C |s2cid=7731172 |issn=0169-6149 |url-access=subscription}}</ref> In a Miller–Urey setup with a less-reducing (CO₂ + N₂ + H₂O) atmosphere, when they added calcium carbonate to buffer the aqueous solution and ascorbic acid to inhibit oxidation, yields of amino acids greatly increased, demonstrating that amino acids can still be formed in more neutral atmospheres under the right geochemical conditions.<ref name="Cleaves-2008"/> In a prebiotic context, they argued that seawater would likely still be buffered and ferrous iron could inhibit oxidation.<ref name="Cleaves-2008"/>

In 1999, after Miller suffered a stroke, he donated the contents of his laboratory to Bada.<ref name="Dreifus-2010"/> In an old cardboard box, Bada discovered unanalyzed samples from modified experiments that Miller had conducted in the 1950s.<ref name="Dreifus-2010"/> In a "volcanic" apparatus, Miller had amended an aspirating nozzle to shoot a jet of steam into the reaction chamber.<ref name="bada20132"/><ref name="Johnson-2008">{{Cite journal |last1=Johnson |first1=Adam P. |last2=Cleaves |first2=H. James |last3=Dworkin |first3=Jason P. |last4=Glavin |first4=Daniel P. |last5=Lazcano |first5=Antonio |last6=Bada |first6=Jeffrey L. |date=2008-10-17 |title=The Miller Volcanic Spark Discharge Experiment |url=https://www.science.org/doi/10.1126/science.1161527 |journal=Science |language=en |volume=322 |issue=5900 |page=404 |doi=10.1126/science.1161527 |pmid=18927386 |bibcode=2008Sci...322..404J |s2cid=10134423 |issn=0036-8075 |url-access=subscription}}</ref> Using high-performance liquid chromatography and mass spectrometry, Bada's lab analyzed old samples from a set of experiments Miller conducted with this apparatus and found some higher yields and a more diverse suite of amino acids.<ref name="bada20132"/><ref name="Johnson-2008"/> Bada speculated that injecting the steam into the spark could have split water into H and OH radicals, leading to more hydroxylated amino acids during Strecker synthesis.<ref name="bada20132"/><ref name="Johnson-2008"/> In a separate set of experiments, Miller added hydrogen sulfide (H₂S) to the reducing atmosphere, and Bada's analyses of the products suggested order-of-magnitude higher yields, including some amino acids with sulfur moieties.<ref name="bada20132"/><ref name="Parker-2011">{{Cite journal |last1=Parker |first1=Eric T. |last2=Cleaves |first2=Henderson J. |last3=Dworkin |first3=Jason P. |last4=Glavin |first4=Daniel P. |last5=Callahan |first5=Michael |last6=Aubrey |first6=Andrew |last7=Lazcano |first7=Antonio |last8=Bada |first8=Jeffrey L. |date=2011-04-05 |title=Primordial synthesis of amines and amino acids in a 1958 Miller H 2 S-rich spark discharge experiment |journal=Proceedings of the National Academy of Sciences |language=en |volume=108 |issue=14 |pages=5526–5531 |doi=10.1073/pnas.1019191108 |issn=0027-8424 |pmc=3078417 |pmid=21422282 |doi-access=free |bibcode=2011PNAS..108.5526P}}</ref>

A 2021 work highlighted the importance of the high-energy free electrons present in the experiment. It is these electrons that produce ions and radicals, and represent an aspect of the experiment that needs to be better understood.<ref>{{Cite journal |last1=Micca Longo |first1=Gaia |last2=Vialetto |first2=Luca |last3=Diomede |first3=Paola |last4=Longo |first4=Savino |last5=Laporta |first5=Vincenzo |date=2021-06-16 |title=Plasma modeling and prebiotic chemistry: A review of the state-of-the-art and perspectives |journal=Molecules |language=en |volume=26 |issue=12 |page=3663 |doi=10.3390/molecules26123663 |doi-access=free |pmid=34208472 |pmc=8235047}}</ref>

After comparing Miller–Urey experiments conducted in borosilicate glassware with those conducted in Teflon apparatuses, a 2021 paper suggests that the glass reaction vessel acts as a mineral catalyst, implicating silicate rocks as important surfaces in prebiotic Miller–Urey reactions.<ref>{{Cite journal |last1=Criado-Reyes |first1=Joaquín |last2=Bizzarri |first2=Bruno M. |last3=García-Ruiz |first3=Juan Manuel |last4=Saladino |first4=Raffaele |last5=Di Mauro |first5=Ernesto |date=2021-10-25 |title=The role of borosilicate glass in Miller–Urey experiment |journal=Scientific Reports |language=en |volume=11 |issue=1 |page=21009 |doi=10.1038/s41598-021-00235-4 |bibcode=2021NatSR..1121009C |issn=2045-2322 |doi-access=free |pmid=34697338 |pmc=8545935}}</ref>

==Early Earth's prebiotic atmosphere== {{See also|Prebiotic atmosphere}} While there is a lack of geochemical observations to constrain the exact composition of the prebiotic atmosphere, recent models point to an early "weakly reducing" atmosphere; that is, early Earth's atmosphere was likely dominated by CO₂ and N₂ and not CH₄ and NH₃ as used in the original Miller–Urey experiment.<ref>{{Cite journal |last1=Zahnle |first1=K. |last2=Schaefer |first2=L. |last3=Fegley |first3=B. |date=2010-10-01 |title=Earth's Earliest Atmospheres |journal=Cold Spring Harbor Perspectives in Biology |language=en |volume=2 |issue=10 |article-number=a004895 |doi=10.1101/cshperspect.a004895 |issn=1943-0264 |pmc=2944365 |pmid=20573713 |bibcode=2010CSHPB...204895Z }}</ref><ref name="Catling-2017">{{Cite book |last1=Catling |first1=David C. |url=https://www.cambridge.org/core/books/atmospheric-evolution-on-inhabited-and-lifeless-worlds/CB3EE1D3F18A1DB234342E1FF410FC61 |title=Atmospheric Evolution on Inhabited and Lifeless Worlds |last2=Kasting |first2=James F. |date=2017 |publisher=Cambridge University Press |isbn=978-0-521-84412-3 |location=Cambridge |doi=10.1017/9781139020558}}</ref> This is explained, in part, by the chemical composition of volcanic outgassing. Geologist William Rubey was one of the first to compile data on gases emitted from modern volcanoes and concluded that they are rich in CO₂, H₂O, and likely N₂, with varying amounts of H₂, sulfur dioxide (SO₂), and H₂S.<ref name="Catling-2017"/><ref>{{Citation |last=Rubey |first=W. W. |title=Development of the Hydrosphere and Atmosphere, with Special Reference to Probable Composition of the Early Atmosphere |date=1955 |journal=Geological Society of America Special Papers |volume=62 |pages=631–650 |doi=10.1130/spe62-p631 |bibcode=1955GSASP..62..631R}}</ref> Therefore, if the redox state of Earth's mantle — which dictates the composition of outgassing – has been constant since formation, then the atmosphere of early Earth was likely weakly reducing, but there are some arguments for a more-reducing atmosphere for the first few hundred million years.<ref name="Catling-2017"/>

While the prebiotic atmosphere could have had a different redox condition than that of the Miller–Urey atmosphere, the modified Miller–Urey experiments described in the above section demonstrated that amino acids can still be abiotically produced in less-reducing atmospheres under specific geochemical conditions.<ref name="bada20132"/><ref name="Miller-1983"/><ref name="Cleaves-2008"/> Furthermore, harkening back to Urey's original hypothesis of a "post-impact" reducing atmosphere,<ref name="Urey-1952"/> a recent atmospheric modeling study has shown that an iron-rich impactor with a minimum mass around 4×10²⁰ – 5×10²¹ kg would be enough to transiently reduce the entire prebiotic atmosphere, resulting in a Miller–Urey-esque H₂-, CH₄-, and NH₃-dominated atmosphere that persists for millions of years.<ref name="Wogan-2023"/> Previous work has estimated from the lunar cratering record and composition of Earth's mantle that between four and seven such impactors reached the Hadean Earth.<ref name="Zahnle-2020"/><ref name="Wogan-2023"/><ref>{{Cite journal |last1=Marchi |first1=S. |last2=Bottke |first2=W. F. |last3=Elkins-Tanton |first3=L. T. |last4=Bierhaus |first4=M. |last5=Wuennemann |first5=K. |last6=Morbidelli |first6=A. |last7=Kring |first7=D. A. |date=2014 |title=Widespread mixing and burial of Earth's Hadean crust by asteroid impacts |url=https://www.nature.com/articles/nature13539 |journal=Nature |language=en |volume=511 |issue=7511 |pages=578–582 |doi=10.1038/nature13539 |pmid=25079556 |bibcode=2014Natur.511..578M |s2cid=205239647 |issn=1476-4687 |url-access=subscription}}</ref> [[File:Three phases of atmospheric evolution after a large asteroid impact on the Hadean Earth.jpg|center|thumb|712x712px|Conceptual figure from Wogan et al. (2023)<ref name="Wogan-2023"/> depicting three stages phases of atmospheric chemistry after a large asteroid impact on the Hadean Earth. In phase 1, the impactor vaporizes the ocean, and H₂ is generated after iron delivered by the impactor reacts with hot steam. In phase 2, H₂ reacts with CO₂ to produce CH₄ while the atmosphere cools for thousands of years and steam condenses to an ocean. Phase 3 represents the Miller–Urey atmosphere that persists for millions of years, where N₂ and CH₄ photochemistry generates HCN. The atmosphere returns to a CO₂ and N₂ dominated atmosphere after H₂ escapes from Earth to space. From: Nicholas F. Wogan ''et al'' 2023 ''Planet. Sci. J.'' 4 169. Licensed under CC-BY 4.0.]] A large factor controlling the redox budget of early Earth's atmosphere is the rate of atmospheric escape of H₂ after Earth's formation. Atmospheric escape – common to young, rocky planets — occurs when gases in the atmosphere have sufficient kinetic energy to overcome gravitational energy.<ref name="Catling">Catling, D., & Kasting, J. (2017). Escape of Atmospheres to Space. In ''Atmospheric Evolution on Inhabited and Lifeless Worlds'' (pp. 129–168). Cambridge: Cambridge University Press. {{doi|10.1017/9781139020558.006}}</ref> It is generally accepted that the timescale of hydrogen escape is short enough such that H₂ made up < 1% of the atmosphere of prebiotic Earth,<ref name="Catling-2017"/> but, in 2005, a hydrodynamic model of hydrogen escape predicted escape rates two orders of magnitude lower than previously thought, maintaining a hydrogen mixing ratio of 30%.<ref>{{Cite journal |last1=Tian |first1=Feng |last2=Toon |first2=Owen B. |last3=Pavlov |first3=Alexander A. |last4=De Sterck |first4=H. |date=2005-05-13 |title=A Hydrogen-Rich Early Earth Atmosphere |url=https://www.science.org/doi/10.1126/science.1106983 |journal=Science |language=en |volume=308 |issue=5724 |pages=1014–1017 |doi=10.1126/science.1106983 |pmid=15817816 |bibcode=2005Sci...308.1014T |s2cid=262262244 |issn=0036-8075 |url-access=subscription}}</ref> A hydrogen-rich prebiotic atmosphere would have large implications for Miller–Urey synthesis in the Hadean and Archean, but later work suggests solutions in that model might have violated conservation of mass and energy.<ref name="Catling"/><ref>{{Cite journal |last1=Kuramoto |first1=Kiyoshi |last2=Umemoto |first2=Takafumi |last3=Ishiwatari |first3=Masaki |date=2013-08-01 |title=Effective hydrodynamic hydrogen escape from an early Earth atmosphere inferred from high-accuracy numerical simulation |url=https://www.sciencedirect.com/science/article/pii/S0012821X13003117 |journal=Earth and Planetary Science Letters |volume=375 |pages=312–318 |doi=10.1016/j.epsl.2013.05.050 |bibcode=2013E&PSL.375..312K |issn=0012-821X |url-access=subscription}}</ref> That said, during hydrodynamic escape, lighter molecules like hydrogen can "drag" heavier molecules with them through collisions, and recent modeling of xenon escape has pointed to a hydrogen atmospheric mixing ratio of at least 1% or higher at times during the Archean.<ref>{{Cite journal |last1=Zahnle |first1=Kevin J. |last2=Gacesa |first2=Marko |last3=Catling |first3=David C. |date=2019-01-01 |title=Strange messenger: A new history of hydrogen on Earth, as told by Xenon |url=https://www.sciencedirect.com/science/article/pii/S0016703718305349 |journal=Geochimica et Cosmochimica Acta |volume=244 |pages=56–85 |doi=10.1016/j.gca.2018.09.017 |arxiv=1809.06960 |bibcode=2019GeCoA.244...56Z |issn=0016-7037}}</ref>

Taken together, the view that early Earth's atmosphere was weakly reducing, with transient instances of highly-reducing compositions following large impacts is generally supported.<ref name="Wogan-2023"/><ref name="Urey-1952"/><ref name="Catling-2017"/>

== Extraterrestrial sources of amino acids == [[File:Murchison crop.jpg|thumb|A sample of the Murchison meteorite on display at the National Museum of Natural History, Washington, D.C.]] Conditions similar to those of the Miller–Urey experiments are present in other regions of the Solar System, often substituting ultraviolet light for lightning as the energy source for chemical reactions.<ref>{{cite journal |last1=Nunn |first1=JF |year=1998 |title=Evolution of the atmosphere |journal=Proceedings of the Geologists' Association. Geologists' Association |volume=109 |issue=1 |pages=1–13 |doi=10.1016/s0016-7878(98)80001-1 |pmid=11543127 |bibcode=1998PrGA..109....1N}}</ref><ref>{{cite journal |last1=Raulin |first1=F |last2=Bossard |first2=A |year=1984 |title=Organic syntheses in gas phase and chemical evolution in planetary atmospheres. |journal=Advances in Space Research |volume=4 |issue=12 |pages=75–82 |bibcode=1984AdSpR...4l..75R |doi=10.1016/0273-1177(84)90547-7 |pmid=11537798}}</ref><ref>{{cite journal |last1=Raulin |first1=François |last2=Brassé |first2=Coralie |last3=Poch |first3=Olivier |last4=Coll |first4=Patrice |year=2012 |title=Prebiotic-like chemistry on Titan |journal=Chemical Society Reviews |volume=41 |issue=16 |pages=5380–93 |doi=10.1039/c2cs35014a |pmid=22481630 |bibcode=2012CSRev..41.5380R }}</ref> The Murchison meteorite that fell near Murchison, Victoria, Australia in 1969 was found to contain an amino acid distribution remarkably similar to Miller–Urey discharge products.<ref name="Dreifus-2010"/> Analysis of the organic fraction of the Murchison meteorite with Fourier-transform ion cyclotron resonance mass spectrometry detected over 10,000 unique compounds,<ref>{{Cite journal |last1=Schmitt-Kopplin |first1=Philippe |last2=Gabelica |first2=Zelimir |last3=Gougeon |first3=Régis D. |last4=Fekete |first4=Agnes |last5=Kanawati |first5=Basem |last6=Harir |first6=Mourad |last7=Gebefuegi |first7=Istvan |last8=Eckel |first8=Gerhard |last9=Hertkorn |first9=Norbert |date=2010-02-16 |title=High molecular diversity of extraterrestrial organic matter in Murchison meteorite revealed 40 years after its fall |journal=Proceedings of the National Academy of Sciences |language=en |volume=107 |issue=7 |pages=2763–2768 |doi=10.1073/pnas.0912157107 |issn=0027-8424 |pmc=2840304 |pmid=20160129 |bibcode=2010PNAS..107.2763S |doi-access=free}}</ref> albeit at very low (ppb–ppm) concentrations.<ref>{{Cite journal |last1=Shock |first1=Everett L. |last2=Schulte |first2=Mitchell D. |date=1990-11-01 |title=Summary and implications of reported amino acid concentrations in the Murchison meteorite |journal=Geochimica et Cosmochimica Acta |volume=54 |issue=11 |pages=3159–3173 |doi=10.1016/0016-7037(90)90131-4 |pmid=11541223 |bibcode=1990GeCoA..54.3159S |issn=0016-7037}}</ref><ref>{{Cite journal |last1=Koga |first1=Toshiki |last2=Naraoka |first2=Hiroshi |date=2017-04-04 |title=A new family of extraterrestrial amino acids in the Murchison meteorite |journal=Scientific Reports |language=en |volume=7 |issue=1 |page=636 |doi=10.1038/s41598-017-00693-9 |bibcode=2017NatSR...7..636K |issn=2045-2322 |doi-access=free |pmid=28377577 |pmc=5428853}}</ref> In this way, the organic composition of the Murchison meteorite is seen as evidence of Miller–Urey synthesis outside Earth.

Comets and other icy outer-solar-system bodies are thought to contain large amounts of complex carbon compounds (such as tholins) formed by processes akin to Miller–Urey setups, darkening surfaces of these bodies.<ref name="Sagan-1979"/><ref>{{cite journal |vauthors=Thompson WR, Murray BG, Khare BN, Sagan C |date=December 1987 |title=Coloration and darkening of methane clathrate and other ices by charged particle irradiation: applications to the outer solar system |journal=Journal of Geophysical Research |volume=92 |issue=A13 |pages=14933–47 |bibcode=1987JGR....9214933T |doi=10.1029/JA092iA13p14933 |pmid=11542127 |title-link=methane clathrate}}</ref> Some argue that comets bombarding the early Earth could have provided a large supply of complex organic molecules along with the water and other volatiles,<ref>{{cite journal |vauthors=Pierazzo E, Chyba CF |year=2010 |title=Amino acid survival in large cometary impacts |journal=Meteoritics & Planetary Science |volume=34 |issue=6 |pages=909–918 |bibcode=1999M&PS...34..909P |doi=10.1111/j.1945-5100.1999.tb01409.x |s2cid=97334519 |doi-access=free}}</ref><ref>{{Cite journal |last1=Chyba |first1=Christopher |last2=Sagan |first2=Carl |date=1992 |title=Endogenous production, exogenous delivery and impact-shock synthesis of organic molecules: an inventory for the origins of life |url=https://www.nature.com/articles/355125a0 |journal=Nature |language=en |volume=355 |issue=6356 |pages=125–132 |doi=10.1038/355125a0 |pmid=11538392 |bibcode=1992Natur.355..125C |s2cid=4346044 |issn=1476-4687 |url-access=subscription}}</ref> however very low concentrations of biologically-relevant material combined with uncertainty surrounding the survival of organic matter upon impact make this difficult to determine.<ref name="Miller"/>

==Relevance to the origin of life== The Miller–Urey experiment was proof that the building blocks of life could be synthesized abiotically from gases, and introduced a new prebiotic chemistry framework through which to study the origin of life. Simulations of protein sequences present in the last universal common ancestor (LUCA), or the last shared ancestor of all extant species today, show an enrichment in simple amino acids that were available in the prebiotic environment according to Miller–Urey chemistry.<ref>{{Cite journal |last1=Wehbi |first1=Sawsan |last2=Wheeler |first2=Andrew |last3=Morel |first3=Benoit |last4=Manepalli |first4=Nandini |last5=Minh |first5=Bui Quang |last6=Lauretta |first6=Dante S. |last7=Masel |first7=Joanna |date=2024-12-24 |title=Order of amino acid recruitment into the genetic code resolved by last universal common ancestor's protein domains |journal=Proceedings of the National Academy of Sciences |volume=121 |issue=52 |article-number=e2410311121 |doi=10.1073/pnas.2410311121 |pmc=11670089 |pmid=39665745 |bibcode=2024PNAS..12110311W}}</ref> This suggests that the genetic code from which all life evolved was rooted in a smaller suite of amino acids than those used today.<ref name="Singh M.-2002">{{cite journal |author1=Brooks D.J. |author2=Fresco J.R. |author3=Lesk A.M. |author4=Singh M. |date=October 1, 2002 |title=Evolution of amino acid frequencies in proteins over deep time: inferred order of introduction of amino acids into the genetic code |url=http://mbe.oupjournals.org/cgi/content/full/19/10/1645 |journal=Molecular Biology and Evolution |volume=19 |issue=10 |pages=1645–55 |doi=10.1093/oxfordjournals.molbev.a003988 |pmid=12270892 |archive-url=https://web.archive.org/web/20041213094516/http://mbe.oupjournals.org/cgi/content/full/19/10/1645 |archive-date=December 13, 2004 |doi-access=free}}</ref><ref>{{Cite journal |last1=Makarov |first1=Mikhail |last2=Sanchez Rocha |first2=Alma C. |last3=Krystufek |first3=Robin |last4=Cherepashuk |first4=Ivan |last5=Dzmitruk |first5=Volha |last6=Charnavets |first6=Tatsiana |last7=Faustino |first7=Anneliese M. |last8=Lebl |first8=Michal |last9=Fujishima |first9=Kosuke |last10=Fried |first10=Stephen D. |last11=Hlouchova |first11=Klara |date=2023-03-08 |title=Early Selection of the Amino Acid Alphabet Was Adaptively Shaped by Biophysical Constraints of Foldability |journal=Journal of the American Chemical Society |volume=145 |issue=9 |pages=5320–5329 |doi=10.1021/jacs.2c12987 |issn=0002-7863 |pmc=10017022 |pmid=36826345 |bibcode=2023JAChS.145.5320M}}</ref> Thus, while creationist arguments focus on the fact that Miller–Urey experiments have not generated all 22 genetically-encoded amino acids,<ref name="creation.com">{{Cite web |title=Why the Miller Urey research argues against abiogenesis |url=https://creation.com/why-the-miller-urey-research-argues-against-abiogenesis |access-date=2023-11-15 |website=creation.com |language=en-gb}}</ref> this does not actually conflict with the evolutionary perspective on the origin of life.<ref>{{Cite journal |last1=Mayer-Bacon |first1=Christopher |last2=Meringer |first2=Markus |last3=Havel |first3=Riley |last4=Aponte |first4=José C. |last5=Freeland |first5=Stephen |title=A Closer Look at Non-random Patterns Within Chemistry Space for a Smaller, Earlier Amino Acid Alphabet |journal=Journal of Molecular Evolution |date=2022 |volume=90 |issue=3–4 |pages=307–323 |doi=10.1007/s00239-022-10061-5 |issn=1432-1432 |pmid=35666290 |bibcode=2022JMolE..90..307M}}</ref><ref>{{Cite journal |last=Kirschning |first=Andreas |date=2022 |title=On the Evolutionary History of the Twenty Encoded Amino Acids |journal=Chemistry – A European Journal |language=en |volume=28 |issue=55 |article-number=e202201419 |doi=10.1002/chem.202201419 |issn=1521-3765 |pmc=9796705 |pmid=35726786 |bibcode=2022ChEuJ..28E1419K}}</ref> [[File:CISS origin of homochirality conceptual figure.jpg|left|thumb|481x481px|Conceptual figure from Ozturk and Sasselov (2022)<ref>{{Cite journal |last1=Ozturk |first1=S. Furkan |last2=Sasselov |first2=Dimitar D. |date=2022-07-12 |title=On the origins of life's homochirality: Inducing enantiomeric excess with spin-polarized electrons |journal=Proceedings of the National Academy of Sciences |language=en |volume=119 |issue=28 |article-number=e2204765119 |doi=10.1073/pnas.2204765119 |doi-access=free |issn=0027-8424 |pmc=9282223 |pmid=35787048 |arxiv=2203.16011 |bibcode=2022PNAS..11904765O}}</ref> of a plausible prebiotic scenario with an enantioselective bias. Irradiation of magnetized magnetite with ultraviolet light generates spin-selective electrons. The helicity of the electrons leads to different redox reaction rates with different stereoisomers, leading to enantioselective products. Mechanisms like these mean that Miller–Urey and other prebiotic syntheses do not need to be enantioselective, as the environment can introduce homochirality. From: Ozturk, S.F. and Sasselov, D.D. On the origins of life's homochirality: inducing enantiomeric excess with spin-polarized electrons. ''Proceedings of the National Academy of Sciences'' 119 (28) e2204765119 (2022). Licensed under CC-BY 4.0.]] Another common criticism is that the racemic mixture (containing both L and D enantiomers) of amino acids produced in a Miller–Urey experiment is not exemplary of abiogenesis theories,<ref name="creation.com"/> as life on Earth today uses almost exclusively L-amino acids.<ref>Nelson, D. L., & Cox, M. M. (2017). ''Lehninger principles of biochemistry'' (7th ed.). W.H. Freeman.</ref> While it is true that Miller–Urey setups produce racemic mixtures,<ref>{{Cite journal |last1=Parker |first1=Eric T. |last2=Cleaves |first2=James H. |last3=Burton |first3=Aaron S. |last4=Glavin |first4=Daniel P. |last5=Dworkin |first5=Jason P. |last6=Zhou |first6=Manshui |last7=Bada |first7=Jeffrey L. |last8=Fernández |first8=Facundo M. |date=2014-01-21 |title=Conducting Miller–Urey Experiments |url=https://www.jove.com/t/51039/conducting-miller--urey-experiments |journal=Journal of Visualized Experiments |volume=83 |language=en |issue=83 |article-number=e51039 |doi=10.3791/51039 |pmid=24473135 |pmc=4089479 |bibcode=2014JVExp..8351039P |issn=1940-087X}}</ref> the origin of homochirality is a separate area in origin of life research.<ref>{{Cite journal |last=Blackmond |first=Donna G. |date=2019 |title=The Origin of Biological Homochirality |journal=Cold Spring Harbor Perspectives in Biology |language=en |volume=11 |issue=3 |article-number=a032540 |doi=10.1101/cshperspect.a032540 |issn=1943-0264 |doi-access=free |pmid=30824575 |pmc=6396334}}</ref>

Recent work demonstrates that magnetic mineral surfaces like magnetite can be templates for the enantioselective crystallization of chiral molecules, including RNA precursors, due to the chiral-induced spin selectivity (CISS) effect.<ref>{{Cite journal |last1=Ozturk |first1=S. Furkan |last2=Liu |first2=Ziwei |last3=Sutherland |first3=John D. |last4=Sasselov |first4=Dimitar D. |date=2023-06-09 |title=Origin of biological homochirality by crystallization of an RNA precursor on a magnetic surface |journal=Science Advances |language=en |volume=9 |issue=23 |article-number=eadg8274 |doi=10.1126/sciadv.adg8274 |issn=2375-2548 |pmc=10246896 |pmid=37285423 |arxiv=2303.01394 |bibcode=2023SciA....9G8274O}}</ref><ref>{{Cite journal |last1=Ozturk |first1=S. Furkan |last2=Bhowmick |first2=Deb Kumar |last3=Kapon |first3=Yael |last4=Sang |first4=Yutao |last5=Kumar |first5=Anil |last6=Paltiel |first6=Yossi |last7=Naaman |first7=Ron |last8=Sasselov |first8=Dimitar D. |date=2023-10-10 |title=Chirality-induced avalanche magnetization of magnetite by an RNA precursor |journal=Nature Communications |language=en |volume=14 |issue=1 |page=6351 |doi=10.1038/s41467-023-42130-8 |pmid=37816811 |pmc=10564924 |arxiv=2304.09095 |bibcode=2023NatCo..14.6351O |issn=2041-1723}}</ref> Once an enantioselective bias is introduced, homochirality can then propagate through biological systems in various ways.<ref>{{Cite journal |last1=Ozturk |first1=S. Furkan |last2=Sasselov |first2=Dimitar D. |last3=Sutherland |first3=John D. |date=2023-08-14 |title=The central dogma of biological homochirality: How does chiral information propagate in a prebiotic network? |journal=The Journal of Chemical Physics |language=en |volume=159 |issue=6 |article-number=061102 |doi=10.1063/5.0156527 |pmid=37551802 |pmc=7615580 |arxiv=2306.01803 |bibcode=2023JChPh.159f1102O |issn=0021-9606}}</ref> In this way, enantioselective synthesis is not required of Miller–Urey reactions if other geochemical processes in the environment are introducing homochirality.

Finally, Miller–Urey and similar experiments primarily deal with the synthesis of monomers; polymerization of these building blocks to form peptides and other more complex structures is the next step of prebiotic chemistry schemes.<ref>{{Cite journal |last1=Pascal |first1=Robert |last2=Chen |first2=Irene A. |date=2019 |title=From soup to peptides |url=https://www.nature.com/articles/s41557-019-0318-6 |journal=Nature Chemistry |language=en |volume=11 |issue=9 |pages=763–764 |doi=10.1038/s41557-019-0318-6 |pmid=31406322 |bibcode=2019NatCh..11..763P |s2cid=199541746 |issn=1755-4349 |url-access=subscription}}</ref> Polymerization requires condensation reactions, which are thermodynamically unfavored in aqueous solutions because they expel water molecules.<ref name="Griffith-2012">{{Cite journal |last1=Griffith |first1=Elizabeth C. |last2=Vaida |first2=Veronica |date=2012-09-25 |title=In situ observation of peptide bond formation at the water–air interface |journal=Proceedings of the National Academy of Sciences |language=en |volume=109 |issue=39 |pages=15697–15701 |doi=10.1073/pnas.1210029109 |issn=0027-8424 |pmc=3465415 |pmid=22927374 |bibcode=2012PNAS..10915697G |doi-access=free}}</ref> Scientists as far back as John Desmond Bernal in the late 1940s thus speculated that clay surfaces would play a large role in abiogenesis, as they might concentrate monomers.<ref>Tirard, S. (2011). Bernal's Conception of Origins of Life. In: Gargaud, M., ''et al.'' Encyclopedia of Astrobiology. Springer, Berlin, Heidelberg. {{doi|10.1007/978-3-642-11274-4_158}}</ref> Several such models for mineral-mediated polymerization have emerged, such as the interlayers of layered double hydroxides like green rust over wet-dry cycles.<ref name="Erastova20172">{{cite journal |vauthors=Erastova V, Degiacomi MT, Fraser D, Greenwell HC |date=December 2017 |title=Mineral surface chemistry control for origin of prebiotic peptides |journal=Nature Communications |volume=8 |issue=1 |article-number=2033 |bibcode=2017NatCo...8.2033E |doi=10.1038/s41467-017-02248-y |pmc=5725419 |pmid=29229963}}</ref> Some scenarios for peptide formation have been proposed that are even compatible with aqueous solutions, such as the hydrophobic air-water interface<ref name="Griffith-2012"/> and a novel "sulfide-mediated α-aminonitrile ligation" scheme, where amino acid precursors come together to form peptides.<ref>{{Cite journal |last1=Canavelli |first1=Pierre |last2=Islam |first2=Saidul |last3=Powner |first3=Matthew W. |date=2019 |title=Peptide ligation by chemoselective aminonitrile coupling in water |url=https://www.nature.com/articles/s41586-019-1371-4 |journal=Nature |language=en |volume=571 |issue=7766 |pages=546–549 |doi=10.1038/s41586-019-1371-4 |pmid=31292542 |s2cid=195873596 |issn=1476-4687}}</ref> Polymerization of life's building blocks is an active area of research in prebiotic chemistry.

==Amino acids identified== {{Category see also|Chemical synthesis of amino acids}}

Below is a table of amino acids produced and identified in the "classic" 1952 experiment, as analyzed by Miller in 1952<ref name="miller19532"/> and more recently by Bada and collaborators with modern mass spectrometry,<ref name="bada20132"/> the 2008 re-analysis of vials from the volcanic spark discharge experiment,<ref name="bada20132"/><ref name="Johnson-2008"/> and the 2010 re-analysis of vials from the H₂S-rich spark discharge experiment.<ref name="bada20132"/><ref name="Parker-2011"/> While not all proteinogenic amino acids have been produced in spark discharge experiments, it is generally accepted that early life used a simpler set of prebiotically-available amino acids.<ref name="Singh M.-2002"/>

{|class="wikitable sortable" style="text-align:right" |- ! scope="col" rowspan="2" | Amino acid ! colspan="4" scope="col" | Produced in experiment ! scope="col" rowspan="2" | Proteinogenic |- ! scope="col" | Miller–Urey<br/>{{small|(1952)}} ! scope="col" | Bada reanalysis of 1950s product<br/>{{small|(2008–)}} ! scope="col" | Volcanic spark discharge<br/>{{small|(2008)}} ! scope="col" | H₂S-rich spark discharge<br/>{{small|(2010)}} |- |Glycine || {{ya}} || {{ya}} || {{ya}} || {{ya}} || {{yes}} |- |α-Alanine || {{ya}} || {{ya}} || {{ya}} || {{ya}} || {{yes}} |- |β-Alanine || {{ya}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |Aspartic acid || {{ya}} || {{ya}} || {{ya}} || {{ya}} || {{yes}} |- |α-Aminobutyric acid || {{ya}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |Serine || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{yes}} |- |Isoserine || {{na}} || {{na}} || {{ya}} || {{ya}} || {{no}} |- |α-Aminoisobutyric acid || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |β-Aminoisobutyric acid || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |β-Aminobutyric acid || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |γ-Aminobutyric acid || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |Valine || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{yes}} |- |Isovaline || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |Glutamic acid || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{yes}} |- |Norvaline || {{na}} || {{ya}} || {{ya}} || {{na}} || {{no}} |- |Methylamine || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |Ethylamine || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |Ethanolamine || {{na}} || {{ya}} || {{ya}} || {{ya}} || {{no}} |- |Isopropylamine || {{na}} || {{ya}} || {{ya}} || {{na}} || {{no}} |- |n-Propylamine || {{na}} || {{ya}} || {{ya}} || {{na}} || {{no}} |- |α-Aminoadipic acid || {{na}} || {{na}} || {{ya}} || {{na}} || {{no}} |- |Homoserine || {{na}} || {{na}} || {{ya}} || {{na}} || {{no}} |- |2-Methylserine || {{na}} || {{na}} || {{ya}} || {{na}} || {{no}} |- |β-Hydroxyaspartic acid || {{na}} || {{na}} || {{ya}} || {{na}} || {{no}} |- |Ornithine || {{na}} || {{na}} || {{ya}} || {{na}} || {{no}} |- |2-Methylglutamic acid || {{na}} || {{na}} || {{ya}} || {{na}} || {{no}} |- |Phenylalanine || {{na}} || {{na}} || {{ya}} || {{na}} || {{yes}} |- |Homocysteic acid || {{na}} || {{na}} || {{na}} || {{ya}} || {{no}} |- |''S''-Methylcysteine || {{na}} || {{na}} || {{na}} || {{ya}} || {{no}} |- |Methionine || {{na}} || {{na}} || {{na}} || {{ya}} || {{yes}} |- |Methionine sulfoxide || {{na}} || {{na}} || {{na}} || {{ya}} || {{no}} |- |Methionine sulfone || {{na}} || {{na}} || {{na}} || {{ya}} || {{no}} |- |Isoleucine || {{na}} || {{na}} || {{na}} || {{ya}} || {{yes}} |- |Leucine || {{na}} || {{na}} || {{na}} || {{ya}} || {{yes}} |- |Ethionine || {{na}} || {{na}} || {{na}} || {{ya}} || {{no}} |- |Cysteine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Histidine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Lysine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Asparagine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Pyrrolysine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Proline || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Glutamine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Arginine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Threonine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Selenocysteine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Tryptophan || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |- |Tyrosine || {{na}} || {{na}} || {{na}} || {{na}} || {{yes}} |}

==References== {{Reflist|30em}}

==External links== * [http://www.millerureyexperiment.com/ The Miller–Urey experiment website], a simulation of the Miller–Urey Experiment along with a video interview with Stanley Miller] by Scott Ellis from CalSpace (UCSD) * [https://web.archive.org/web/20081019122408/http://www.pubs.acs.org/cen/news/86/i42/8642notw4.html Origin-Of-Life Chemistry Revisited: Reanalysis of famous spark-discharge experiments reveals a richer collection of amino acids were formed.] * [https://web.archive.org/web/20090821213017/http://www.chem.duke.edu/~jds/cruise_chem/Exobiology/miller.html Miller–Urey experiment explained] * [https://althofer.de/miller-experiment-with-lego.html Miller experiment with Lego bricks] * [https://www.pbs.org/exploringspace/meteorites/murchison/page5.html "Stanley Miller's Experiment: Sparking the Building Blocks of Life" on PBS] * {{cite journal |title=The origin of life and the nature of the primitive gene |journal=Journal of Theoretical Biology |volume=10 |issue=1 |pages=53–88 |year=1966 |last1=Cairns-Smith |first1=A.G. |bibcode=1966JThBi..10...53C|pmid=5964688 |doi=10.1016/0022-5193(66)90178-0}} * [https://web.archive.org/web/20090321030328/http://astrobiology.gsfc.nasa.gov/analytical/PDF/Johnsonetal2008.pdf Details of 2008 re-analysis]

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