Editing Miller–Urey experiment (section)

== Related experiments and follow-up work ==

=== Contemporary experiments ===
[[File:Huygens_surface_color_enhanced.jpg|thumb|324x324px|The surface of [[Titan (moon)|Titan]] as viewed from the [[Huygens (spacecraft)|''Huygens'' lander]]. [[Tholin]]s, complex particles formed by UV irradiation on the N<sub>2</sub> and CH<sub>4</sub> 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 "[[resin]]ous 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 |pages=603}}</ref><ref>{{Cite news |title=Looking Back Two Billion Years |language=en |work=The New York Times |url=http://timesmachine.nytimes.comhttp//timesmachine.content-tagging.us-east-1-01.prd.dvsp.nyt.net/timesmachine/1953/03/08/92690093.html?pageNumber=159 |access-date=2023-11-14}}</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]] (CO<sub>2</sub>) 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 CO<sub>2</sub>, <sub>2</sub>O Mixtures in a High-Frequency Electric Arc |journal=[[Science (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 NH<sub>3</sub> 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 [[Nucleobase|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 |pages=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 [[Ultraviolet|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 |url=https://dx.doi.org/10.1016/0301-9268%2883%2990068-2 |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|url-access=subscription }}</ref> For example, UV-photolysis of water vapor with [[carbon monoxide]] was found to yield various [[Alcohol (chemistry)|alcohols]], aldehydes, and [[organic acid]]s.<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 |url=https://doi.org/10.1007%2FBF00931407 |journal=Origins of Life |volume=9 |issue=2 |pages=93–101 |bibcode=1978OrLi....9...93B |doi=10.1007/BF00931407 |pmid=752138 |s2cid=33972427|url-access=subscription }}</ref> In the 1970s, [[Carl Sagan]] used Miller-Urey-type reactions to synthesize and experiment with complex organic particles dubbed "[[tholin]]s", which likely resemble particles formed in hazy atmospheres like that of [[Titan (moon)|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 H<sub>2</sub>, H<sub>2</sub>O, N<sub>2</sub>, CO<sub>2</sub> or CH<sub>4</sub>, and sometimes NH<sub>3</sub>.<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 |url=https://dx.doi.org/10.1016/0273-1177%2883%2990040-6 |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|url-access=subscription }}</ref> They found that the presence or absence of NH<sub>3</sub> in the mixture did not significantly impact amino acid yield, as NH<sub>3</sub> was generated from N<sub>2</sub> during the spark discharge.<ref name="Miller-1983" /> Additionally, CH<sub>4</sub> 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 CH<sub>4</sub>, but similar yields could be reached with a high H<sub>2</sub>/CO<sub>2</sub> 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 L. Bada|Jeffrey Bada]] and H. James Cleaves, graduate students of Miller, hypothesized that the production of nitrites, which destroy amino acids, in CO<sub>2</sub> and N<sub>2</sub>-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 (CO<sub>2</sub> + N<sub>2</sub> + H<sub>2</sub>O) atmosphere, when they added [[calcium carbonate]] to [[Buffer (chemistry)|buffer]] the aqueous solution and [[Chemistry of ascorbic acid|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 [[Geochemistry|geochemical]] conditions.<ref name="Cleaves-2008" /> In a prebiotic context, they argued that seawater would likely still be buffered and [[Iron(II) compounds|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 "[[Volcano|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 |pages=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 [[Hydroxylation|hydroxylated]] amino acids during Strecker synthesis.<ref name="bada20132" /><ref name="Johnson-2008" /> In a separate set of experiments, Miller added [[hydrogen sulfide]] (H<sub>2</sub>S) to the reducing atmosphere, and Bada's analyses of the products suggested order-of-magnitude higher yields, including some amino acids with [[sulfur]] [[Moiety (chemistry)|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 }}</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 |pages=3663 |doi=10.3390/molecules26123663 |doi-access=free|pmid=34208472 |pmc=8235047 }}</ref>

After comparing Miller–Urey experiments conducted in [[borosilicate glass]]ware with those conducted in [[Polytetrafluoroethylene|Teflon]] apparatuses, a 2021 paper suggests that the glass reaction vessel acts as a mineral [[Catalysis|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 |pages=21009 |doi=10.1038/s41598-021-00235-4 |bibcode=2021NatSR..1121009C |issn=2045-2322|doi-access=free |pmid=34697338 |pmc=8545935 }}</ref>