{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T17:02:59Z","timestamp":1781110979036,"version":"3.54.1"},"reference-count":58,"publisher":"National Academy of Sciences","issue":"15","license":[{"start":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T00:00:00Z","timestamp":1743984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","award":["31145"],"award-info":[{"award-number":["31145"]}],"id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"HHS | NIH | National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA029971"],"award-info":[{"award-number":["AA029971"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"HHS | NIH | National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA030115"],"award-info":[{"award-number":["AA030115"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"HHS | NIH | National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA04510"],"award-info":[{"award-number":["DA04510"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000027","name":"HHS | NIH | National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["AA031124"],"award-info":[{"award-number":["AA031124"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000888","name":"W. M. Keck Foundation","doi-asserted-by":"publisher","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100000888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,4,15]]},"abstract":"<jats:p>\n                    Interest in the biological actions of alcohols, ethanol in particular, dates back to the earliest historical texts. Alcohol research is now a highly active field with roots in physiology, pharmacology, toxicology, and neuroscience. But at what point did interest and speculation evolve into bona fide science? Here, we set out to identify the earliest systematic empirical investigations into the biological actions of alcohols and unearthed a surprisingly rigorous literature which included a fundamental insight with significant implications for modern research and policy. Through manual backward citation mapping of archived texts, much of which was digitally inaccessible, we outline the origins of alcohol research beginning with a transcribed lecture from Benjamin Ward Richardson in 1869. In the years immediately following, the field of alcohol research was legitimized around what came to be briefly known as \u201cRichardson\u2019s law.\u201d Richardson\u2019s law states that the acute toxicity of straight-chain monohydroxy alcohols is directly proportional to the carbon chain length of the molecule. This law was recognized only briefly not because it was disproven, but rather because it was simply forgotten during the decades that passed between its inception and the advent of systematic bibliographic databases which paved the way for digital archiving. Quantitative analysis of studies spanning a century revealed that across monohydroxy alcohols with one (methanol) to thirteen (tridecanol) carbons, there is a near-deterministic relationship between chain-length and lethal dose (R\n                    <jats:sup>2<\/jats:sup>\n                    = 0.96). Richardson\u2019s law of alcohol potency has silently stood the test of time and is among functional biology\u2019s oldest and least challenged scientific laws.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2318863122","type":"journal-article","created":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T15:01:45Z","timestamp":1744038105000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Richardson\u2019s law and the origins of alcohol research"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5359-3087","authenticated-orcid":false,"given":"Snigdha","family":"Mukerjee","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University","place":["Nashville"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9871-2089","authenticated-orcid":false,"given":"Cody A.","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Vanderbilt Brain Institute, Vanderbilt Center for Addiction Research, Vanderbilt University","place":["Nashville"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"e_1_3_4_1_2","first-page":"703","article-title":"Physiological research on alcohols","volume":"2","author":"Richardson B. W.","year":"1869","unstructured":"B. W. Richardson, Physiological research on alcohols. The Medical Times and Gazette 2, 703\u2013706 (1869).","journal-title":"The Medical Times and Gazette"},{"key":"e_1_3_4_2_2","first-page":"555","article-title":"XXVII. Researches on a new class of alcohols","volume":"147","author":"Hofmann A. W. V.","year":"1857","unstructured":"A. W. V. Hofmann, A. Cahours, XXVII. Researches on a new class of alcohols. Abstr. Pap. Print. Philos. Trans. R. Soc. Lond. 147, 555\u2013574 (1857).","journal-title":"Abstr. Pap. Print. Philos. Trans. R. Soc. Lond."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1098\/rspl.1856.0010"},{"key":"e_1_3_4_4_2","unstructured":"B. W. Richardson \"Report on the physiological action of certain compounds of amyl and ethyl\u201d in British Association for the Advancement of Science 36th Meeting Report (1867) pp. 172\u2013179."},{"key":"e_1_3_4_5_2","first-page":"478","article-title":"Researches on the treatment of suspended animation","volume":"31","author":"Richardson B. W.","year":"1863","unstructured":"B. W. Richardson, Researches on the treatment of suspended animation. Br Foreign Med. Chir Rev. 31, 478\u2013505 (1863).","journal-title":"Br Foreign Med. Chir Rev."},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)49759-0"},{"key":"e_1_3_4_7_2","first-page":"20","article-title":"On the theory of Zymosis","volume":"1","author":"Richardson B. W.","year":"1860","unstructured":"B. W. Richardson, On the theory of Zymosis. Trans Epidemiol. Soc. Lond 1, 20\u201330 (1860).","journal-title":"Trans Epidemiol. Soc. Lond"},{"key":"e_1_3_4_8_2","first-page":"44","article-title":"The jubilee of an\u00e6sthesia","volume":"21","author":"Richardson B. W.","year":"1896","unstructured":"B. W. Richardson, The jubilee of an\u00e6sthesia. Hosp. (Lond.) 21, 44\u201345 (1896).","journal-title":"Hosp. (Lond.)"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1163\/22977953-0450304005"},{"key":"e_1_3_4_10_2","volume-title":"On Alcohol: A Course of Six Cantor Lectures Delivered Before the Society of Arts","author":"Richardson B. W.","year":"1876","unstructured":"B. W. Richardson, On Alcohol: A Course of Six Cantor Lectures Delivered Before the Society of Arts (National Temperance Society & Publication House, 1876)."},{"key":"e_1_3_4_11_2","unstructured":"Wikipedia contributors Benjamin Ward Richardson Wikipedia The Free Encyclopedia. (2024) https:\/\/en.wikipedia.org\/w\/index.php?title=Benjamin_Ward_Richardson&oldid=1216628773."},{"key":"e_1_3_4_12_2","volume-title":"Fifty Years of Food Reform: A History of the Vegetarian Movement in England","author":"Forward C. W.","year":"1898","unstructured":"C. W. Forward, Fifty Years of Food Reform: A History of the Vegetarian Movement in England (Ideal Pub. Union, 1898)."},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.328.421"},{"key":"e_1_3_4_14_2","first-page":"259","article-title":"Report on the physiological action of the methyl and allied series","volume":"2","author":"Richardson B. W.","year":"1869","unstructured":"B. W. Richardson, Report on the physiological action of the methyl and allied series. Medical Times and Gazette 2, 259\u2013260 (1869).","journal-title":"Medical Times and Gazette"},{"key":"e_1_3_4_15_2","first-page":"719","article-title":"Chloral and other narcotics","volume":"35","author":"Richardson B. W.","year":"1879","unstructured":"B. W. Richardson, Chloral and other narcotics. Contemp. Rev. 35, 719\u2013739 (1879).","journal-title":"Contemp. Rev."},{"key":"e_1_3_4_16_2","first-page":"387","article-title":"The ethylates, or caustic alcohols","volume":"16","author":"Richardson B. W.","year":"1894","unstructured":"B. W. Richardson, The ethylates, or caustic alcohols. Hosp. (Lond.) 16, 387 (1894).","journal-title":"Hosp. (Lond.)"},{"key":"e_1_3_4_17_2","first-page":"441","article-title":"Potassium ethylate","volume":"16","author":"Richardson B. W.","year":"1894","unstructured":"B. W. Richardson, Potassium ethylate. Hosp. (Lond.) 16, 441 (1894).","journal-title":"Hosp. (Lond.)"},{"key":"e_1_3_4_18_2","volume-title":"Ten Lectures on Alcohol","author":"Richardson B. W.","year":"2022","unstructured":"B. W. Richardson, Ten Lectures on Alcohol (Legare Street Press, 2022)."},{"key":"e_1_3_4_19_2","volume-title":"The Action of Alcohol on the Mind","author":"Richardson B. W.","year":"1877","unstructured":"B. W. Richardson, The Action of Alcohol on the Mind (W. Tweedie, 1877)."},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1911.sp001475"},{"key":"e_1_3_4_21_2","unstructured":"Teaching about evolution and the nature of science National Academies of Sciences Engineering and Medicine (The National Academies Press 1998)."},{"key":"e_1_3_4_22_2","unstructured":"National Research Council The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research (The National Academies Press 2008)."},{"key":"e_1_3_4_23_2","first-page":"474","volume-title":"The Oxford Companion to Philosophy","author":"Honderich T.","year":"1995","unstructured":"T. Honderich, The Oxford Companion to Philosophy (Oxford University Press, London, England, ed. 1, 1995), pp. 474\u2013476."},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)09270-5"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0147-6513(90)90026-2"},{"key":"e_1_3_4_26_2","first-page":"985","article-title":"Narcotic and toxic potency of aliphatic alcohols upon rabbits","volume":"10","author":"Munch J. C.","year":"1925","unstructured":"J. C. Munch, E. W. Schwartze, Narcotic and toxic potency of aliphatic alcohols upon rabbits. J. Lab. Clin. Med. 10, 985\u2013996 (1925).","journal-title":"J. Lab. Clin. Med."},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0045-6535(92)90287-2"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)05703-9"},{"key":"e_1_3_4_29_2","unstructured":"W. F. von Oettingen The Aliphatic Alcohols: Their Toxicity and Potential Dangers in Relation to their Chemical Constitution and their Fate in Metabolism (United States Government Printing Office 1943)."},{"key":"e_1_3_4_30_2","unstructured":"National Institute for Occupational Safety and Health The Registry of Toxic Effects of Chemical Substances (RTECS). https:\/\/dnacih.com\/niosh\/nioshdbs\/rtecs\/start.htm. Deposited June 2005."},{"key":"e_1_3_4_31_2","first-page":"321","article-title":"QSAR analysis and data extrapolation among mammals in a series of aliphatic alcohols","volume":"61","author":"Tich\u00fd M.","year":"1985","unstructured":"M. Tich\u00fd, V. Trcka, Z. Roth, M. Krivucov\u00e1, QSAR analysis and data extrapolation among mammals in a series of aliphatic alcohols. Environ. Health Perspect. 61, 321\u2013328 (1985).","journal-title":"Environ. Health Perspect."},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.5962\/bhl.title.33119"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.738.236"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1537-2197.1933.tb08880.x"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1537-2197.1934.tb04993.x"},{"key":"e_1_3_4_36_2","volume-title":"Dialogues on Drink","author":"Richardson B. W.","year":"1882","unstructured":"B. W. Richardson, Dialogues on Drink (National Temperance and Publishing House, 1882)."},{"key":"e_1_3_4_37_2","first-page":"141","article-title":"The Physical Foundations of Temperance","volume":"27","author":"Richardson B. W.","year":"1895","unstructured":"B. W. Richardson, The Physical Foundations of Temperance. Longman\u2019s magazine, 1882-1905 27, 141\u2013157 (1895).","journal-title":"Longman\u2019s magazine, 1882-1905"},{"key":"e_1_3_4_38_2","volume-title":"Total Abstinence","author":"Richardson B. W.","year":"1878","unstructured":"B. W. Richardson, Total Abstinence (Macmillan, 1878)."},{"key":"e_1_3_4_39_2","first-page":"235","article-title":"Physiological theory and therapeutic explanation in the 1860s: The British debate on the medical use of alcohol","volume":"54","author":"Warner J. H.","year":"1980","unstructured":"J. H. Warner, Physiological theory and therapeutic explanation in the 1860s: The British debate on the medical use of alcohol. Bull. Hist. Med. 54, 235\u2013257 (1980).","journal-title":"Bull. Hist. Med."},{"key":"e_1_3_4_40_2","unstructured":"\u201cPhysics 1928\u201d in Physics 1922-1941: Nobel Lectures Including Presentation Speeches and Laureates\u2019 Biographies (Elsevier Publishing Company 1965) pp. 219\u2013238."},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2007.12.008"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-17900-1_78"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-021-03202-0"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/prac.18691070161"},{"key":"e_1_3_4_45_2","volume-title":"Studien \u00fcber die Narkose: zugleich ein Beitrag zur allgemeinen Pharmakologie","author":"Overton C. E.","year":"1901","unstructured":"C. E. Overton, Studien \u00fcber die Narkose: zugleich ein Beitrag zur allgemeinen Pharmakologie (G. Fischer, 1901)."},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(86)90298-1"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(25)32727-8"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.24.040184.000355"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/245154a0"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-28720-6_143"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.105148"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1080\/02652038809373713"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.3390\/pr8121609"},{"key":"e_1_3_4_54_2","volume-title":"Chemical Composition of Alcoholic Beverages, Additives and Contaminants","author":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans","year":"1988","unstructured":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, Chemical Composition of Alcoholic Beverages, Additives and Contaminants (International Agency for Research on Cancer, 1988)."},{"key":"e_1_3_4_55_2","doi-asserted-by":"crossref","unstructured":"S. Harrison \u201cChapter 10 - Quality control: Methods of analysis\u201d in Distilled Spirits A. Hill F. Jack Eds. (Academic Press 2023) pp. 251\u2013276.","DOI":"10.1016\/B978-0-12-822443-4.00007-4"},{"key":"e_1_3_4_56_2","doi-asserted-by":"publisher","DOI":"10.3390\/nu14183873"},{"key":"e_1_3_4_57_2","unstructured":"27 CFR 7.145 Malt beverages containing less than 0.5 percent alcohol by volume. Available at: https:\/\/www.ecfr.gov\/current\/title-27\/chapter-I\/subchapter-A\/part-7\/subpart-I\/section-7.145 [Accessed 3 February 2025]."},{"key":"e_1_3_4_58_2","first-page":"376","article-title":"Vote of thanks to Dr. Richardson for his lectures","volume":"2","author":"Wells T. S.","year":"1869","unstructured":"T. S. Wells, Vote of thanks to Dr. Richardson for his lectures. Medical Times and Gazette 2, 376 (1869).","journal-title":"Medical Times and Gazette"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2318863122","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T15:05:49Z","timestamp":1744038349000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2318863122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,7]]},"references-count":58,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2025,4,15]]}},"alternative-id":["10.1073\/pnas.2318863122"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2318863122","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,7]]},"assertion":[{"value":"2025-04-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2318863122"}}