Editing Circadian rhythm (section)

==History==
The earliest recorded account of a circadian process is credited to [[Theophrastus]], dating from the 4th century BC, probably provided to him by report of [[Androsthenes of Thasos|Androsthenes]], a [[Sea captain|ship's captain]] serving under [[Alexander the Great]]. In his book, 'Περὶ φυτῶν ἱστορία', or 'Enquiry into plants', Theophrastus describes a "tree  with many leaves like the [[rose]], and that this closes at night, but opens at sunrise, and by noon is completely unfolded; and at evening again it closes by degrees and remains shut at night, and the natives say that it goes to sleep."<ref>{{cite web | vauthors = ((Theophrastus, 'Περὶ φυτῶν ἱστορία')) | title = Enquiry into plants and minor works on odours and weather signs, with an English translation by Sir Arthur Hort, bart 1916 | url = https://www.biodiversitylibrary.org/bibliography/27820 | archive-url = https://web.archive.org/web/20220413104526/https://www.biodiversitylibrary.org/bibliography/27820 | archive-date=2022-04-13 }}</ref> The tree mentioned by him was much later identified as the [[tamarind]] tree by the botanist, H Bretzl, in his book on the botanical findings of the Alexandrian campaigns.<ref>{{Cite book | vauthors = Bretzl H |title=Botanische Forschungen des Alexanderzuges | url = https://archive.org/details/b2486903x |location=Leipzig |publisher=Teubner |year=1903}}{{Page needed|date=September 2010}}</ref>

The observation of a circadian or diurnal process in humans is mentioned in [[History of Chinese medicine|Chinese medical texts]] dated to around the 13th century, including the ''Noon and Midnight Manual'' and the ''Mnemonic Rhyme to Aid in the Selection of Acu-points According to the Diurnal Cycle, the Day of the Month and the Season of the Year''.<ref name="cl">{{cite book| vauthors = Lu GD |title=Celestial Lancets|date=25 October 2002|publisher=Psychology Press|isbn=978-0-7007-1458-2|pages=137–140}}</ref>

In 1729, French scientist [[Jean-Jacques d'Ortous de Mairan]] conducted the first experiment designed to distinguish an endogenous clock from responses to daily stimuli. He noted that 24-hour patterns in the movement of the leaves of the plant ''[[Mimosa pudica]]'' persisted, even when the plants were kept in constant darkness.<ref name="de mairan 1729">{{Cite journal | vauthors = de Mairan JJ | title=Observation Botanique | journal=Histoire de l'Académie Royale des Sciences | year=1729 | pages=35–36}}</ref><ref name="pmid16761955">{{cite journal | vauthors = Gardner MJ, Hubbard KE, Hotta CT, Dodd AN, Webb AA | title = How plants tell the time | journal = The Biochemical Journal | volume = 397 | issue = 1 | pages = 15–24 | date = July 2006 | pmid = 16761955 | pmc = 1479754 | doi = 10.1042/BJ20060484 }}</ref>

In 1896, Patrick and Gilbert observed that during a prolonged period of [[sleep deprivation]], sleepiness increases and decreases with a period of approximately 24 hours.<ref>{{cite journal | vauthors = Dijk DJ, von Schantz M | title = Timing and consolidation of human sleep, wakefulness, and performance by a symphony of oscillators | journal = Journal of Biological Rhythms | volume = 20 | issue = 4 | pages = 279–290 | date = August 2005 | pmid = 16077148 | doi = 10.1177/0748730405278292 | s2cid = 13538323 | doi-access = free }}</ref> In 1918, [[J.S. Szymanski]] showed that animals are capable of maintaining 24-hour activity patterns in the absence of external cues such as light and changes in temperature.<ref>{{Cite journal | vauthors = Danchin A |title=Important dates 1900–1919 |journal=HKU-Pasteur Research Centre |url=http://www.pasteur.fr/recherche/unites/REG/causeries/dates_1900.html |archive-url=https://web.archive.org/web/20031020031510/http://www.pasteur.fr/recherche/unites/REG/causeries/dates_1900.html |url-status=dead |archive-date=2003-10-20 |access-date=2008-01-12 }}</ref>

In the early 20th century, circadian rhythms were noticed in the rhythmic feeding times of bees. [[Auguste Forel]], [[Ingeborg Beling]], and Oskar Wahl conducted numerous experiments to determine whether this rhythm was attributable to an endogenous clock.<ref>{{cite journal | vauthors = Antle MC, Silver R | title = Neural basis of timing and anticipatory behaviors | journal = The European Journal of Neuroscience | volume = 30 | issue = 9 | pages = 1643–1649 | date = November 2009 | pmid = 19878281 | pmc = 2929840 | doi = 10.1111/j.1460-9568.2009.06959.x }}</ref> The existence of circadian rhythm was independently discovered in [[Drosophila melanogaster|fruit flies]] in 1935 by two German zoologists, [[Hans Kalmus]] and [[Erwin Bünning]].<ref>{{cite journal| vauthors = Bruce VG, Pittendrigh CS |title=Endogenous Rhythms in Insects and Microorganisms|journal=The American Naturalist|date=1957|volume=91|issue=858|pages=179–195|doi=10.1086/281977|bibcode=1957ANat...91..179B |s2cid=83886607}}</ref><ref name=pitt93>{{cite journal | vauthors = Pittendrigh CS | title = Temporal organization: reflections of a Darwinian clock-watcher | journal = Annual Review of Physiology | volume = 55 | issue = 1 | pages = 16–54 | date = 1993 | pmid = 8466172 | doi = 10.1146/annurev.ph.55.030193.000313 | s2cid = 45054898 }}</ref>

In 1954, an important experiment reported by [[Colin Pittendrigh]] demonstrated that [[eclosion]] (the process of [[pupa]] turning into adult) in ''[[Drosophila pseudoobscura]]'' was a circadian behaviour. He demonstrated that while temperature played a vital role in eclosion rhythm, the period of eclosion was delayed but not stopped when temperature was decreased.<ref>{{cite journal | vauthors = Pittendrigh CS | title = On Temperature Independence in the Clock System Controlling Emergence Time in Drosophila | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 40 | issue = 10 | pages = 1018–1029 | date = October 1954 | pmid = 16589583 | pmc = 534216 | doi = 10.1073/pnas.40.10.1018 | doi-access = free | bibcode = 1954PNAS...40.1018P }}</ref><ref name=pitt93/>

The term ''circadian'' was coined by [[Franz Halberg]] in 1959.<ref>{{cite journal | vauthors = Halberg F, Cornélissen G, Katinas G, Syutkina EV, Sothern RB, Zaslavskaya R, Halberg F, Watanabe Y, Schwartzkopff O, Otsuka K, Tarquini R, Frederico P, Siggelova J | title = Transdisciplinary unifying implications of circadian findings in the 1950s | journal = Journal of Circadian Rhythms | volume = 1 | issue = 1 | pages = 2 | date = October 2003 | pmid = 14728726 | pmc = 317388 | doi = 10.1186/1740-3391-1-2 | quote = Eventually I reverted, for the same reason, to "circadian" ... | doi-access = free }}</ref> According to Halberg's original definition:
{{Blockquote|The term "circadian" was derived from ''circa'' (about) and ''dies'' (day); it may serve to imply that certain physiologic periods are close to 24 hours, if not exactly that length. Herein, "circadian" might be applied to all "24-hour" rhythms, whether or not their periods, individually or on the average, are different from 24 hours, longer or shorter, by a few minutes or hours.<ref>{{cite journal | vauthors = Halberg F | title = [Physiologic 24-hour periodicity; general and procedural considerations with reference to the adrenal cycle] | journal = Internationale Zeitschrift für Vitaminforschung. Beiheft | volume = 10 | pages = 225–296 | date = 1959 | pmid = 14398945 }}</ref><ref name="kouk">{{cite book| vauthors = Koukkari WL, Sothern RB |title=Introducing Biological Rhythms: A Primer on the Temporal Organization of Life, with Implications for Health, Society, Reproduction, and the Natural Environment|date=2006|publisher=Springer|location=New York|isbn=978-1-4020-3691-0|page=23|url=https://books.google.com/books?id=jQWVfKcdct8C}}</ref>}}

In 1977, the International Committee on Nomenclature of the [[International Society for Chronobiology]] formally adopted the definition:
{{Blockquote|Circadian: relating to biologic variations or rhythms with a frequency of 1 cycle in 24 ± 4 h; ''circa'' (about, approximately) and ''dies'' (day or 24 h). Note: term describes rhythms with an about 24-h cycle length, whether they are frequency-synchronized with (acceptable) or are desynchronized or free-running from the local environmental time scale, with periods of slightly yet consistently different from 24-h.<ref>{{cite journal | vauthors = Halberg F, Carandente F, Cornelissen G, Katinas GS | title = [Glossary of chronobiology (author's transl)] | journal = Chronobiologia | volume = 4 | issue = Suppl 1 | pages = 1–189 | date = 1977 | pmid = 352650 }}</ref>}}

[[Ron Konopka]] and [[Seymour Benzer]] identified the first clock mutation in ''Drosophila'' in 1971, naming the gene "[[period (gene)|period]]" (''per'') gene, the first discovered genetic determinant of behavioral rhythmicity.<ref name="pmid5002428">{{cite journal | vauthors = Konopka RJ, Benzer S | title = Clock mutants of Drosophila melanogaster | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 68 | issue = 9 | pages = 2112–2116 | date = September 1971 | pmid = 5002428 | pmc = 389363 | doi = 10.1073/pnas.68.9.2112 | doi-access = free | bibcode = 1971PNAS...68.2112K }}</ref> The ''per'' gene was isolated in 1984 by two teams of researchers. Konopka, Jeffrey Hall, Michael Roshbash and their team showed that ''per'' locus is the centre of the circadian rhythm, and that loss of ''per'' stops circadian activity.<ref name=reddy>{{cite journal | vauthors = Reddy P, Zehring WA, Wheeler DA, Pirrotta V, Hadfield C, Hall JC, Rosbash M | title = Molecular analysis of the period locus in Drosophila melanogaster and identification of a transcript involved in biological rhythms | journal = Cell | volume = 38 | issue = 3 | pages = 701–710 | date = October 1984 | pmid = 6435882 | doi = 10.1016/0092-8674(84)90265-4 | s2cid = 316424 }}</ref><ref name=zehring>{{cite journal | vauthors = Zehring WA, Wheeler DA, Reddy P, Konopka RJ, Kyriacou CP, Rosbash M, Hall JC | title = P-element transformation with period locus DNA restores rhythmicity to mutant, arrhythmic Drosophila melanogaster | journal = Cell | volume = 39 | issue = 2 Pt 1 | pages = 369–376 | date = December 1984 | pmid = 6094014 | doi = 10.1016/0092-8674(84)90015-1 | doi-access = free }}</ref>  At the same time, Michael W. Young's team reported similar effects of ''per'', and that the gene covers 7.1-kilobase (kb) interval on the X chromosome and encodes a 4.5-kb poly(A)+ RNA.<ref name=bargi1>{{cite journal | vauthors = Bargiello TA, Jackson FR, Young MW | title = Restoration of circadian behavioural rhythms by gene transfer in Drosophila | journal = Nature | volume = 312 | issue = 5996 | pages = 752–754 | date = 1984 | pmid = 6440029 | doi = 10.1038/312752a0 | s2cid = 4259316 | bibcode = 1984Natur.312..752B }}</ref><ref name=bargi2>{{cite journal | vauthors = Bargiello TA, Young MW | title = Molecular genetics of a biological clock in Drosophila | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 81 | issue = 7 | pages = 2142–2146 | date = April 1984 | pmid = 16593450 | pmc = 345453 | doi = 10.1038/312752a0 | bibcode = 1984Natur.312..752B }}</ref> They went on to discover the key genes and neurones in ''Drosophila'' circadian system, for which Hall, Rosbash and Young received the [[Nobel Prize in Physiology or Medicine|Nobel Prize in Physiology or Medicine 2017]].<ref name="nobel17">{{Cite web|title=The Nobel Prize in Physiology or Medicine 2017|url=https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/|access-date=2017-10-06|website=www.nobelprize.org}}</ref>

[[Joseph Takahashi]] discovered the first mammalian circadian clock mutation (''clockΔ19'') using mice in 1994.<ref>{{MEDRS|date=November 2013}} {{Cite news |title=Gene Discovered in Mice that Regulates Biological Clock |work=Chicago Tribune |date=29 April 1994}}</ref><ref>{{primary source inline|date=November 2013}} {{cite journal | vauthors = Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, Takahashi JS | title = Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior | journal = Science | volume = 264 | issue = 5159 | pages = 719–725 | date = April 1994 | pmid = 8171325 | pmc = 3839659 | doi = 10.1126/science.8171325 | bibcode = 1994Sci...264..719H }}</ref> However, recent studies show that deletion of ''clock'' does not lead to a behavioral phenotype (the animals still have normal circadian rhythms), which questions its importance in rhythm generation.<ref>{{cite journal | vauthors = Debruyne JP, Noton E, Lambert CM, Maywood ES, Weaver DR, Reppert SM | title = A clock shock: mouse CLOCK is not required for circadian oscillator function | journal = Neuron | volume = 50 | issue = 3 | pages = 465–477 | date = May 2006 | pmid = 16675400 | doi = 10.1016/j.neuron.2006.03.041 | s2cid = 19028601 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Collins B, Blau J | title = Keeping time without a clock | journal = Neuron | volume = 50 | issue = 3 | pages = 348–350 | date = May 2006 | pmid = 16675389 | doi = 10.1016/j.neuron.2006.04.022 | doi-access = free }}</ref>

The first human clock mutation was identified in an extended Utah family by Chris Jones, and genetically characterized by Ying-Hui Fu and Louis Ptacek. Affected individuals are extreme '[[Lark (person)|morning larks]]' with 4-hour advanced sleep and other rhythms. This form of [[familial advanced sleep phase syndrome]] is caused by a single [[amino acid]] change, S662➔G, in the human PER2 protein.<ref>{{cite journal | vauthors = Toh KL, Jones CR, He Y, Eide EJ, Hinz WA, Virshup DM, Ptácek LJ, Fu YH | title = An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome | journal = Science | volume = 291 | issue = 5506 | pages = 1040–1043 | date = February 2001 | pmid = 11232563 | doi = 10.1126/science.1057499 | s2cid = 1848310 | bibcode = 2001Sci...291.1040T }}</ref><ref>{{cite journal | vauthors = Jones CR, Campbell SS, Zone SE, Cooper F, DeSano A, Murphy PJ, Jones B, Czajkowski L, Ptácek LJ | title = Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans | journal = Nature Medicine | volume = 5 | issue = 9 | pages = 1062–1065 | date = September 1999 | pmid = 10470086 | doi = 10.1038/12502 | s2cid = 14809619 }}</ref>