extended notes

INTRODUCTION

This page will be intermittently updated.

x This can sabotage sleep: A small sample of the studies that draw these connections: Junyan Duan, Elyse Noelani Greenberg, Satya Swaroop Karri, and Bogi Andersen, “The Circadian Clock and Diseases of the Skin,” FEBS Letters 595, no. 19 (October 2021): 2413–36, doi.org/10.1002/1873‑3468.14192; Junghyun Noh. “The Effect of Circadian and Sleep Disruptions on Obesity Risk.” Journal of Obesity & Metabolic Syndrome 27, no. 2 (2018): 78–83. doi:10.7570/jomes.2018.27.2.78; Ayesha A. Shafi and Karen E. Knudsen. “Cancer and the Circadian Clock.” Cancer Research 79, no. 15 (2019): 3806–14. doi:10.1158/0008-5472.CAN-19-0566; Sarah L. Chellappa, Nina Vujovic, Jonathan S. Williams, and Frank A. J. L. Scheer, “Impact of Circadian Disruption on Cardiovascular Function and Disease,” Trends in Endocrinology and Metabolism 30, no. 10 (October 2019): 767–79, doi.org/10.1016/j.tem.2019.07.008; Robin M. Voigt, Christopher B. Forsyth, and Ali Keshavarzian, “Circadian Rhythms: A Regulator of Gastrointestinal Health and Dysfunction,” Expert Review of Gastroenterology & Hepatology 13, no. 5 (March 2019): 411–24, doi.org/10.1080/17474124.2019.1595588; Peeraporn Varinthra and Ingrid Y. Liu. “Molecular Basis for the Association between Depression and Circadian Rhythm.” Tzu Chi Medical Journal 31, no. 2 (April-June 2019): 67–72. doi:10.4103/tcmj.tcmj_181_18.

x The consequences of circadian disruption: Peng Zhang et al., “Environmental Perturbation of the Circadian Clock during Pregnancy Leads to Transgenerational Mood Disorder‑like Behaviors in Mice,” Scientific Reports 7, no. 1 (October 2017): 12641, doi.org/10.1038/s41598‑017‑13067‑y.

xii implantable and ingestible bioelectronic: “DARPA Program to Build Travel Adapter for Human Body.” n.d. Darpa.Mil. Accessed October 13, 2023. https://www.darpa.mil/news-events/2020-04-06.

xii How about the 99 percent: Fabio Falchi et al., “The New World Atlas of Artificial Night Sky Brightness,” Science Advances 2, no. 6 (June 2016): e1600377, doi.org/10.1126/sciadv.1600377.

xii while a fetus is in the womb: Wayne I. L.Davies, Soufien Sghari, Brian A. Upton, Christoffer Nord, Max Hahn, Ulf Ahlgren, Richard A. Lang, and Lena Gunhaga. “Distinct Opsin 3 (Opn3) Expression in the Developing Nervous System during Mammalian Embryogenesis.” ENeuro 8, no. 5 (2021): ENEURO.0141-21.2021. doi:10.1523/ENEURO.0141-21.2021.

xii composition of microbial squatters: Yueliang Zhang et al., “The Microbiome Stabilizes Circadian Rhythms in the Gut,” Proceedings of the National Academy of Sciences of the United States of America 120, no. 5 (January 2023), e2217532120, doi.org/10.1073/pnas.2217532120.

xii restricting meals to daylight: Emily N. C. Manoogian et al., “Time‑Restricted Eating for the Prevention and Management of Metabolic Diseases,” Endocrine Re- views 43, no. 2 (April 2022): 405–36, doi.org/10.1210/endrev/bnab027.

xii Even adjusting the time chemotherapy: Pasquale F. Innominato et al., “The Future of Precise Cancer Chronotherapeutics,” Lancet Oncology 23, no. 6 (June 2022): e242, doi.org/10.1016/S1470‑2045(22)00188‑7.

xiii Our immune system is under: Christoph Scheiermann, Yuya Kunisaki, and Paul S. Frenette, “Circadian Control of the Immune System,” Nature Reviews Immunology 13, no. 3 (March 2013): 190–98, doi.org/10.1038/nri3386.

xvi Some moves are surprisingly simple: Jennifer Hahn‑Holbrook et al., “Human Milk as ‘Chrononutrition’: Implications for Child Health and Development,” Pediat- ric Research 85, no. 7 (June 2019): 936–42, doi.org/10.1038/s41390‑019‑0368‑x.

CHAPTER 1. Losing time

7 color least likely: “Module 2. How Shift Work and Long Work Hours Increase Health and Safety Risks,” in NIOSH Training for Nurses on Shift Work and Long Work Hours, National Institute for Occupational Safety and Health, 2020, accessed April 2, 2020, cdc.gov/niosh/work‑hour‑training‑for‑nurses/longhours/mod2/20.html.

11 all three mutations: Ronald J. Konopka and Seymour Benzer, “Clock Mutants of Drosophila melanogaster,” Proceedings of the National Academy of Sciences of the United States of America 68, no. 9 (September 1971): 2112–16, doi.org/10.1073/pnas.68.9.2112.

11 “stumbled straight into the center”: Jonathan Weiner, Time, Love, Memory: A Great Biologist and His Quest for the Origins of Behavior (New York: Alfred A. Knopf, 1999).

13 On July 16, 1962: Michel Siffre, Beyond Time (London: Chatto and Windus, 1965).

14 “My co‑workers and I”: Jürgen Aschoff, “Circadian Rhythms in Man,” Science 148, no. 3676 (1965): 1427–32, doi.org/10.1126/science.148.3676.1427.

14 Aschoff’s team asked participants: The researchers made the bunker apartments as comfortable as possible. There was a bedroom with a cushioned chair, table, and desk. There was a shower and a small kitchen. Artificial lights could be turned on and off. This would become a source of criticism among scientists who feared partici‑ pants’ control of the lights altered outcomes.

15 more stringent restrictions: Wei Wang, Robin K. Yuan, Jude F. Mitchell, Kirsi-Marja Zitting, Melissa A. St Hilaire, James K. Wyatt, Frank A. J. L. Scheer, et al. “Desynchronizing the Sleep—Wake Cycle from Circadian Timing to Assess Their Separate Contributions to Physiology and Behaviour and to Estimate Intrinsic Circadian Period.” Nature Protocols 18, no. 2 (2023): 579–603. doi:10.1038/s41596-022-00746-y.; Kenneth P.Wright, Jr, Rod J. Hughes, Richard E. Kronauer, Derk-Jan Dijk, and Charles A. Czeisler. “Intrinsic Near-24-h Pacemaker Period Determines Limits of Circadian Entrainment to a Weak Synchronizer in Humans.” Proceedings of the National Academy of Sciences of the United States of America 98, no. 24 (2001): 14027–32. doi:10.1073/pnas.201530198.

15 Charles Czeisler, a sleep and circadian researcher: Kenneth P. Wright Jr. et al., “Intrinsic Near‑24‑h Pacemaker Period Determines Limits of Circadian Entrainment to a Weak Synchronizer in Humans,” Proceedings of the National Academy of Sciences of the United States of America 98, no. 24 (November 2001): 14027–32, doi. org/10.1073/pnas.201530198.

15 widely considered the most: J. F. Duffy et al., “Sex Difference in the Near‑24‑Hour Intrinsic Period of the Human Circadian Timing System,” Proceedings of the National Academy of Sciences of the United States of America 108, Supplement 3, (September 2011), doi:10.1073/pnas.1010666108.

CHAPTER 2. what makes you tick?

This chapter leans largely on history lessons from several circadian scientists, including Vincent Cassone, a biologist at the University of Kentucky, and William Schwartz, a neu‑ roscientist at The University of Texas at Austin. Several sources are available for a deeper dig into the history, such as: William J. Schwartz and Serge Daan, “Origins: A Brief Account of the Ancestry of Circadian Biology,” in Biological Timekeeping: Clocks, Rhythms and Behaviour (New Delhi: Springer, India, 2017), 3–22.

27 When mammals first arose: Roi Maor, Tamar Dayan, Henry Ferguson-Gow, and Kate E. Jones. “Temporal Niche Expansion in Mammals from a Nocturnal Ancestor after Dinosaur Extinction.” Nature Ecology & Evolution 1, no. 12 (2017): 1889–95. doi:10.1038/s41559-017-0366-5.

28 I doubt anyone would pay: Filipa Rijo‑Ferreira and Joseph S. Takahashi, “Sleeping Sickness: A Tale of Two Clocks,” Frontiers in Cellular and Infection Microbiology 10 (October 2020): 525097, doi.org/10.3389/fcimb.2020.525097; Filipa Rijo-Ferreira, Daniel Pinto-Neves, Nuno L. Barbosa-Morais, Joseph S. Takahashi, and Luisa M. Figueiredo. “Trypanosoma Brucei Metabolism Is under Circadian Control.” Nature Microbiology 2, no. 6 (2017): 17032. doi:10.1038/nmicrobiol.2017.32.; Filipa Rijo-Ferreira and Joseph S. Takahashi.

29 Our strength generally maxes out: Collin M. Douglas, Stuart J. Hesketh, and Karyn A. Esser, “Time of Day and Muscle Strength: A Circadian Output?,” Physiology 36, no. 1 (January 2021): 44–51, doi.org/10.1152/physiol.00030.2020.

29 sleep through the night: Lisa R.Stow and Michelle L. Gumz. “The Circadian Clock in the Kidney.” Journal of the American Society of Nephrology: JASN 22, no. 4 (2011): 598–604. doi:10.1681/ASN.2010080803.; Stewart Ramsay and Vladimir Zagorodnyuk. “Role of Circadian Rhythms and Melatonin in Bladder Function in Heath and Diseases.” Autonomic Neuroscience: Basic & Clinical 246, no. 103083 (2023): 103083. doi:10.1016/j.autneu.2023.103083; Kim, Su Jin, Jin Wook Kim, Young Sam Cho, Kyung Jin Chung, Hana Yoon, and Khae Hawn Kim. 2019. “Influence of Circadian Disruption Associated with Artificial Light at Night on Micturition Patterns in Shift Workers.” International Neurourology Journal 23 (4): 258–64. https://doi.org/10.5213/inj.1938236.118; Ramsay, Stewart, and Vladimir Zagorodnyuk. 2023.

29 rev you up: Sharon Chan and Miguel Debono. “Review: Replication of Cortisol Circadian Rhythm: New Advances in Hydrocortisone Replacement Therapy.” Therapeutic Advances in Endocrinology and Metabolism 1, no. 3 (2010): 129–38. doi:10.1177/2042018810380214.

29 wax and wane: A sample of this literature: Colleen A. McClung. “How Might Circadian Rhythms Control Mood? Let Me Count the Ways.” Biological Psychiatry 74, no. 4 (2013): 242–49. doi:10.1016/j.biopsych.2013.02.019.; Scheer, Frank A. J. L., Christopher J. Morris, and Steven A. Shea. “The Internal Circadian Clock Increases Hunger and Appetite in the Evening Independent of Food Intake and Other Behaviors.” Obesity (Silver Spring, Md.) 21, no. 3 (2013): 421–23. doi:10.1002/oby.20351.; Christoph Scheiermann, Yuya Kunisaki, and Paul S. Frenette. “Circadian Control of the Immune System.” Nature Reviews. Immunology 13, no. 3 (2013): 190–98. doi:10.1038/nri3386.; Jörg Morf and Ueli Schibler. “Body Temperature Cycles: Gatekeepers of Circadian Clocks.” Cell Cycle (Georgetown, Tex.) 12, no. 4 (2013): 539–40. doi:10.4161/cc.23670.

29 Circadian rhythms could serve: Henrik Oster, Erik Maronde, and Urs Albrecht, “The Circadian Clock as a Molecular Calendar,” Chronobiology International 19, no. 3 (May 2002): 507–16, doi.org/10.1081/CBI‑120004210.

30 It’s a strategy reminiscent of: William Rowan, “Light and Seasonal Reproduction in Animals,” Biological Reviews of the Cambridge Philosophical Society 13, no. 4 (Oc‑ tober 1938): 374–401, doi:10.1111/j.1469‑185x.1938.tb00523.x.

31 That’s when Jean‑Jacques d’Ortous: Jean‑Jacques d’Ortous de Mairan, “Obser‑ vation Botanique,” Histoire de l’Academie Royale des Sciences (January 1729): 35. Translated from the French.

33 paper published in 1898: John H. Schaffner, “Observations on the Nutation of Helianthus annuus,” Botanical Gazette 25, no. 6 (June 1898): 395–403, jstor.org/stable/2464526.

34 Harmer and her team concluded: Hagop S. Atamian et al., “Circadian Regulation of Sunflower Heliotropism, Floral Orientation, and Pollinator Visits,” Science 353, no. 6299 (August 2016): 587–90, doi.org/10.1126/science.aaf9793.

37 Among the first brains: Junko Nishiitsutsuji‑Uwo and Colin S. Pittendrigh, “Central Nervous System Control of Circadian Rhythmicity in the Cockroach: III. The Optic Lobes, Locus of the Driving Oscillation?,” Journal of Comparative Physiology 58, no. 1 (March 1968): 14–46, doi.org/10.1007/BF00302434; Friedrich K. Stephan and Irving Zucker, “Circadian Rhythms in Drinking Behavior and Locomotor Ac‑ tivity of Rats Are Eliminated by Hypothalamic Lesions,” Proceedings of the National Academy of Sciences of the United States of America 69, no. 6 (June 1972): 1583–86, doi.org/10.1073/pnas.69.6.1583; and Curt P. Richter, “‘Dark‑Active’ Rat Trans‑ formed into ‘Light‑Active’ Rat by Destruction of 24‑Hr Clock: Function of 24‑Hr Clock and Synchronizers,” Proceedings of the National Academy of Sciences of the United States of America 75, no. 12 (December 1978): 6276–80, doi.org/10.1073/ pnas.75.12.6276.

37 abandoned outhouse: Circadian. “Colin Pittendrigh (Part 1): An Historical Overview of Circadian Biology.” Youtube, March 10, 2014.

37 suprachiasmatic nucleus: David R. Weaver. “The Suprachiasmatic Nucleus: A 25-Year Retrospective.” Journal of Biological Rhythms 13, no. 2 (1998): 100–112. doi:10.1177/074873098128999952.

38 A series of complex: Michael H. Hastings, Elizabeth S. Maywood, and Marco Brancaccio, “The Mammalian Circadian Timing System and the Suprachiasmatic Nu‑ cleus as Its Pacemaker,” Biology 8, no. 1 (March 2019): 13, doi.org/10.3390/biology8010013.

39 This push‑and‑pull process: While the dogma remains in the field that circadian rhythms are driven by so‑called transcription‑translation feedback loops, some scientists suggest that the concept might not be sufficient or even necessary to explain daily rhythms in our physiology. A few studies show that rhythmic protein activity alone can generate daily rhythms. Redundant processes may reinforce each other to increase circadian robustness. As this science continues to evolve, we’ll focus pri‑ marily on the output of this “black box.” Alessandra Stangherlin, Estere Seinkmane, and John S. O’Neill, “Understanding Circadian Regulation of Mammalian Cell Function, Protein Homeostasis, and Metabolism,” Current Opinion in Systems Biol- ogy 28 (December 2021): 100391, doi.org/10.1016/j.coisb.2021.100391.

39 still in the womb: Keenan Bates and Erik D. Herzog, “Maternal‑Fetal Circadian Communication during Pregnancy,” Frontiers in Endocrinology 11 (April 2020): 198, doi.org/10.3389/fendo.2020.00198.

39 patients with schizophrenia: Madeline R.Scott, Wei Zong, Kyle D. Ketchesin, Marianne L. Seney, George C. Tseng, Bokai Zhu, and Colleen A. McClung, “Twelve‑ Hour Rhythms in Transcript Expression within the Human Dorsolateral Prefrontal Cortex Are Altered in Schizophrenia,” PLoS Biology 21, no. 1 (January 2023): e3001 688, doi:10.1371/journal.pbio.3001688.

40 Scientists disagree on whether: Many scientists suggest that cyanobacteria or something similar likely evolved the first circadian clock. However, other lifeforms may have still independently evolved clocks that converged on the same basic time‑ keeping properties.

40 “If life exists on other”: Hans P. A. Van Dongen et al., “A Circadian Biosignature in the Labeled Release Data from Mars?,” in “Astrobiology and Planetary Missions,” ed. Richard B. Hoover, Gilbert V. Levin, Alexei Y. Rozanov, and G. Randall Glad‑ stone, Proceedings of SPIE 5906 (September 2005): 107–16.

41 By adding three more proteins: Archana G. Chavan et al., “Reconstitution of an Intact Clock Reveals Mechanisms of Circadian Timekeeping,” Science 374, no. 6564 (October 2021): eabd4453, doi.org/10.1126/science.abd4453.

43 His lab followed up: Jérôme Wuarin et al., “The Role of the Transcriptional Activator Protein DBP in Circadian Liver Gene Expression,” in “Transcriptional Regu‑ lation in Cell Differentiation and Development,” ed. Peter Rigby, Robb Krumlauf, and Frank Grosveld, supplement, Journal of Cell Science, no. Supplement 16 (January 1992): 123–27; Jérôme Wuarin and Ueli Schibler, “Expression of the Liver‑Enriched Transcriptional Activator Protein DBP Follows a Stringent Circadian Rhythm,” Cell 63, no. 6 (1990): 1257–66, doi:10.1016/0092‑8674(90)90421‑a.

43 Scientists including Michael Menaker: S. Yamazaki et al., “Resetting Central and Peripheral Circadian Oscillators in Transgenic Rats,” Science 288, no. 5466 (April 2000): 682–85, doi:10.1126/science.288.5466.682.

43 approximately ten trillion cells: Our bodies contain about thirty trillion cells. Approximately twenty trillion of these are red blood cells, which lack a nucleus and therefore circadian clock machinery. The activity of red blood cells does still follow a daily rhythm, however, presumably as a downstream effect of clocks in other cells. And then there are the trillions of bacteria cells we also harbor.

43 As the clock genes: Clock genes can do more than just inform circadian timing, which can complicate the interpretation of research studies that link circadian clock function to various health conditions. Ray Zhang et al., “A Circadian Gene Expression Atlas in Mammals: Implications for Biology and Medicine,” Proceedings of the National Academy of Sciences of the United States of America 111, no. 45 (2014): 16219–24, doi.org/10.1073/pnas.1408886111; and Kimberly H. Cox and Joseph S. Takahashi, “Circadian Clock Genes and the Transcriptional Architecture of the Clock Mechanism,” Journal of Molecular Endocrinology 63, no. 4 (November 2019): R93–102, doi:10.1530/JME‑19‑0153.

43 Each of the twenty thousand: David K. Welsh, Joseph S. Takahashi, and Steve A. Kay, “Suprachiasmatic Nucleus: Cell Autonomy and Network Properties,” Annual Review of Physiology 72 (March 2010): 551–77, doi.org/10.1146/annurev‑physiol‑021909‑135919.

44 relays clock-syncing messages: Roy, Ranjan K., Yifan Yao, Isabella K. Green, Andrew V. Aitken, Vinicia C. Biancardi, Rae Silver, and Javier E. Stern. 2024. “Blood Flows from the SCN toward the OVLT within a New Brain Vascular Portal Pathway.” Science Advances 10 (25): eadn8350. https://doi.org/10.1126/sciadv.adn8350.

44 Instead, an elaborate web: Maria A. Nohales. “Spatial Organization and Coordination of the Plant Circadian System.” Genes 12, no. 3 (2021): 442. doi:10.3390/genes12030442.

CHAPTER 3. power hours

48 From that data, Ptacek: C. R. Jones et al., “Familial Advanced Sleep‑Phase Syndrome: A Short‑Period Circadian Rhythm Variant in Humans,” Nature Medicine 5, no. 9 (September 1999): 1062–65, doi.org/10.1038/12502.

51 sleep is of a higher quality: Andrew J. K. Phillips et al., “Irregular Sleep/Wake Patterns Are Associated with Poorer Academic Performance and Delayed Circadian and Sleep/Wake Timing,” Scientific Reports 7, no. 1 (June 2017): 3216, doi.org/10.1038/s41598‑ 017‑ 03171‑4; and Matthew D. Weaver et al., “Adverse Impact of Polyphasic Sleep Patterns in Humans: Report of the National Sleep Foundation Sleep Timing and Variability Consensus Panel,” Sleep Health 7, no. 3 (June 2021): 293–302, doi.org/10.1016/j.sleh.2021.02.009.

53 Researchers found that members: David R. Samson et al., “Chronotype Variation Drives Night‑Time Sentinel‑like Behaviour in Hunter–Gatherers,” Proceedings of the Royal Society B: Biological Sciences 284, no. 1858 (July 2017): 20170967, doi.org/10.1098/rspb.2017.0967.

54 Neanderthal gene variants: Velazquez-Arcelay, Keila, Laura L. Colbran, Evonne McArthur, Colin M. Brand, David C. Rinker, Justin K. Siemann, Douglas G. McMahon, and John A. Capra. 2023. “Archaic Introgression Shaped Human Circadian Traits.” Genome Biology and Evolution 15 (12). https://doi.org/10.1093/gbe/evad203.

54 circadian rhythms of twins: Nicola L. Barclay, Nathaniel F. Watson, Dedra Buchwald, and Jack Goldberg. “Moderation of Genetic and Environmental Influences on Diurnal Preference by Age in Adult Twins.” Chronobiology International 31, no. 2 (2014): 222–31. doi:10.3109/07420528.2013.842924.

54 The modern chronotype curve has: Several papers coauthored by Till Roenne‑ berg describe the epidemiology of our chronotypes and the implications of this di‑ versity, including Till Roenneberg et al., “Epidemiology of the Human Circadian Clock,” Sleep Medicine Reviews 11, no. 6 (December 2007): 429–38, doi.org/10.1016/j.smrv.2007.07.005; and Till Roenneberg, Eva C. Winnebeck, and Elizabeth B. Klerman, “Daylight Saving Time and Artificial Time Zones—a Battle between Biological and Social Times,” Frontiers in Physiology 10 (August 2019): 944, doi.org/10.3389/fphys.2019.00944.

56 Just a few days: Ellen R. Stothard et al., “Circadian Entrainment to the Natural Light‑Dark Cycle across Seasons and the Weekend,” Current Biology 27, no. 4 (Feb‑ ruary 2017): 508–13, doi.org/10.1016/j.cub.2016.12.041.

57 In our later years: Russell Foster, Life Time: The New Science of the Body Clock, and How It Can Revolutionize Your Sleep and Health (London: Penguin Life, 2022), 182.

57 between the sexes: Jessica A. Mong, Fiona C. Baker, Megan M. Mahoney, Ketema N. Paul, Michael D. Schwartz, Kazue Semba, and Rae Silver. “Sleep, Rhythms, and the Endocrine Brain: Influence of Sex and Gonadal Hormones.” The Journal of Neuroscience: The Official Journal of the Society for Neuroscience 31, no. 45 (2011): 16107–16. doi:10.1523/jneurosci.4175-11.2011; Fischer, Dorothee, David A. Lombardi, Helen Marucci-Wellman, and Till Roenneberg. 2017. “Chronotypes in the US – Influence of Age and Sex.” PloS One 12 (6): e0178782. https://doi.org/10.1371/journal.pone.0178782.

57 Roenneberg and his colleagues coined: Marc Wittmann, Jenny Dinich, Martha Merrow, and Till Roenneberg, “Social Jetlag: Misalignment of Biological and Social Time,” Chronobiology International 23, no. 1–2 (2006): 497–509.

58 The consequences accumulate: Till Roenneberg, “How Can Social Jetlag Affect Health?” Nature Reviews Endocrinology 19, no. 7 (July 2023): 383–84, doi.org/ 10.1038/s41574‑023‑00851‑2; Till Roenneberg, Karla V. Allebrandt, Martha Mer‑ row, and Céline Vetter, “Social Jetlag and Obesity,” Current Biology 22, no. 10 (May 2012): 939–43, doi.org/10.1016/j.cub.2012.03.038; and Sara Gamboa Madeira et al., “Social Jetlag, a Novel Predictor for High Cardiovascular Risk in Blue‑Collar Workers Following Permanent Atypical Work Schedules,” Journal of Sleep Research 30, no. 6 (December 2021): e13380, doi.org/10.1111/jsr.13380.

58 Slightly more common than FASP: This condition goes by many names, including delayed sleep phase disorder. Gian Carlo G. Parico et al., “The Human CRY1 Tail Controls Circadian Timing by Regulating Its Association with CLOCK:BMAL1,” Proceedings of the National Academy of Sciences of the United States of America 117, no. 45 (November 2020): 27971–79, doi.org/10.1073/pnas.1920653117.

59 showed nearly normal rhythms: Alina Patke, Patricia J. Murphy, Onur Emre Onat, Ana C. Krieger, Tayfun Özçelik, Scott S. Campbell, and Michael W. Young. “Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder.” Cell 169, no. 2 (2017): 203-215.e13. doi:10.1016/j.cell.2017.03.027.

61 soak up the sun: Junyan Duan, Elyse Noelani Greenberg, Satya Swaroop Karri, and Bogi Andersen. “The Circadian Clock and Diseases of the Skin.” FEBS Letters 595, no. 19 (2021): 2413–36. doi:10.1002/1873-3468.14192.

62 good and bad times naturally differ: Elisa R. Facer-Childs, Sophie Boiling, and George M. Balanos. “The Effects of Time of Day and Chronotype on Cognitive and Physical Performance in Healthy Volunteers.” Sports Medicine – Open 4, no. 1 (2018). doi:10.1186/s40798-018-0162-z.

62 Tommasi and his colleagues: Alessio Gaggero and Denni Tommasi, “Time of Day and High‑Stake Cognitive Assessments,” Economic Journal 133, no. 652 (May 2023): 1407–29, doi.org/10.1093/ej/ueac090.

62 Circadian variation across the day: Carolyn B. Hines, “Time‑of‑Day Effects on Human Performance,” Journal of Catholic Education 7, no. 3 (2004): 390–413, doi:10.15365/joce.0703072013.

63 likelihood that we act morally: Brian C. Gunia, Christopher M. Barnes, and Sunita Sah, “The Morality of Larks and Owls: Unethical Behavior Depends on Chronotype as Well as Time of Day,” Psychological Science 25, no. 12 (December 2014): 2272–74, doi.org/10.1177/0956797614541989.

63 “flash of illuminance”: Mareike B. Wieth and Rose T. Zacks, “Time of Day Effects on Problem Solving: When the Non‑optimal Is Optimal,” Thinking & Reasoning 17, no. 4 (2011): 387–401, doi.org/10.1080/13546783.2011.625663; and Janet Metcalfe and David Wiebe, “Intuition in Insight and Noninsight Problem Solving,” Memory & Cognition 15, no. 3 (May 1987): 238–46, doi.org/10.3758/BF03197722. Quoted in Daniel Pink, When: The Scientific Secrets of Perfect Timing (New York: Riverhead, 2018), 24.

63 If you’re more interested: Shogo Sato et al., “Atlas of Exercise Metabolism Reveals Time‑Dependent Signatures of Metabolic Homeostasis,” Cell Metabolism 34, no. 2 (February 2022): 329–345.e8, doi.org/10.1016/j.cmet.2021.12.016.

63 Morning workouts appear best: Gali Albalak, Marjon Stijntjes, David van Bodegom, J. Wouter Jukema, Douwe E. Atsma, Diana van Heemst, and Raymond Noordam. “Setting Your Clock: Associations between Timing of Objective Physical Activity and Cardiovascular Disease Risk in the General Population.” European Journal of Preventive Cardiology 30, no. 3 (2023): 232–40. doi:10.1093/eurjpc/zwac239.

63 Yet exercise in the afternoon: Rodrigo Mancilla, Bram Brouwers, Vera B. Schrauwen-Hinderling, Matthijs K. C. Hesselink, Joris Hoeks, and Patrick Schrauwen. “Exercise Training Elicits Superior Metabolic Effects When Performed in the Afternoon Compared to Morning in Metabolically Compromised Humans.” Physiological Reports 8, no. 24 (2021). doi:10.14814/phy2.14669.; Jeroen H.P.M. van der Velde, Sebastiaan C. Boone, Esther Winters-van Eekelen, Matthijs K. C. Hesselink, Vera B. Schrauwen-Hinderling, Patrick Schrauwen, Hildo J. Lamb, Frits R. Rosendaal, and Renée de Mutsert. “Timing of Physical Activity in Relation to Liver Fat Content and Insulin Resistance.” Diabetologia 66, no. 3 (2023): 461–71. doi:10.1007/s00125-022-05813-3.

64 an athlete’s performance: Elise Facer‑Childs and Roland Brandstaetter, “The Impact of Circadian Phenotype and Time since Awakening on Diurnal Performance in Athletes,” Current Biology 25, no. 4 (February 2015): 518–22, doi.org/10.1016/j.cub.2014.12.036.

65 McHill could finally tease apart: Andrew W. McHill and Evan D. Chinoy, “Utilizing the National Basketball Association’s COVID‑19 Restart ‘Bubble’ to Uncover the Impact of Travel and Circadian Disruption on Athletic Performance,” Scientific Reports 10, no. 1 (December 2020): 21827, doi.org/10.1038/s41598‑020‑78901‑2.

66 “one of the worst kept secret[s] in sports”: Meeta Singh, Stephen Bird, Jonathan Charest, Thomas Huyghe, and Julio Calleja-Gonzalez. “Urgent Wake up Call for the National Basketball Association.” Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine 17, no. 2 (2021): 243–48. doi:10.5664/jcsm.8938.

66 Mah collaborated with ESPN: Baxter Holmes, “How Fatigue Shaped the NBA Season, and What It Means for the Playoffs,” ESPN, April 10, 2018, espn.com/nba/story/_/id/23094298/how‑fatigue‑shaped‑nba‑season‑means‑playoffs.

67 One study found MLB teams: The researchers did not analyze game times and, therefore, couldn’t tease out the impact of circadian timing. Alex Song, Thomas Severini, and Ravi Allada, “How Jet Lag Impairs Major League Baseball Performance,” Proceedings of the National Academy of Sciences of the United States of America 114, no. 6 (January 2017): 1407–12, doi:10.1073/pnas.1608847114.

67 Here again, West Coast teams enjoyed a significant edge: Roger S. Smith, Bradley Efron, Cheri D. Mah, and Atul Malhotra. “The Impact of Circadian Misalignment on Athletic Performance in Professional Football Players.” Sleep 36, no. 12 (2013): 1999–2001. doi:10.5665/sleep.3248.

67 West Coast teamsl: R. S. Smith, C. Guilleminault, and B. Efron. “Circadian Rhythms and Enhanced Athletic Performance in the National Football League.” Sleep 20, no. 5 (1997): 362–65.

68 When researchers considered chronotype: Facer‑Childs and Brandstaetter, “The Impact of Circadian Phenotype and Time since Awakening on Diurnal Performance in Athletes.” Current Biology: CB 25, no. 4 (2015): 518–22. doi:10.1016/j.cub.2014.12.036.

CHAPTER 4. rhythm and blues

76 Yet, despite the mice’s blindness: Clyde Keeler referred to “rodless” mice. Because cones would have been extremely difficult to discriminate with technology at the time, Ignacio Provencio noted that Keeler most likely meant photoreceptor‑less mice—or mice deficient in both rods and cones. Clyde E. Keeler, “On the Occurrence in the House Mouse of Mendelizing Structural Defect of the Retina Producing Blindness,” Proceedings of the National Academy of Sciences of the United States of America 12, no. 4 (1926): 255–58, doi:10.1073/pnas.12.4.255; and Clyde E. Keeler, “Iris Movements in Blind Mice,” American Journal of Physiology 81, no. 1 (June 1927): 107–12, doi.org/10.1152/ajplegacy.1927.81.1.107.

76 the idea of a third photoreceptor: Some researchers prefer to call this the fifth photoreceptor, since there are three types of cone cells in the human eye.

76 Foster and his team went: M. S. Freedman et al., “Regulation of Mammalian Circadian Behavior by Non‑rod, Non‑cone, Ocular Photoreceptors,” Science 284, no. 5413 (April 1999): 502–4, doi/10.1126/science.284.5413.502.

76 Scientists including Foster: Farhan H. Zaidi et al., “Short‑Wavelength Light Sensitivity of Circadian, Pupillary, and Visual Awareness in Humans Lacking an Outer Retina,” Current Biology 17, no. 24 (December 2007): 2122–28, doi.org/10.1016/ j.cub.2007.11.034.

77 a “third eye” of sorts: S. Doyle and M. Menaker, “Circadian Photoreception in Ver‑ tebrates,” Cold Spring Harbor Symposia on Quantitative Biology 72, no. 1 (2007): 499–508, doi:10.1101/sqb.2007.72.003; Vincent M. Cassone, “Avian Circadian Or‑ ganization: A Chorus of Clocks,” Frontiers in Neuroendocrinology 35, no. 1 (January 2014): 76–88, doi:10.1016/j.yfrne.2013.10.002.

78 Provencio named it melanopsin: Ignacio Provencio et al., “Melanopsin: An Opsin in Melanophores, Brain, and Eye,” Proceedings of the National Academy of Sciences of the United States of America 95, no. 1 (January 1998): 340 – 45, doi.org/10.1073/pnas.95.1.340.

78 Other investigators followed: D. M. Berson, F. A. Dunn, and M. Takao, “Phototransduction by Retinal Ganglion Cells That Set the Circadian Clock,” Science 295, no. 5557 (February 2002): 1070–73, doi.org/10.1126/science.1067262; and S. Hattar, H. W. Liao, M. Takao, D. M. Berson, and K. W. Yau, “Melanopsin‑Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity,” Science 295, no. 5557 (February 2002): 1065–70, doi.org/10.1126/science.1069609.

78 pump out melatonin: Darkness triggers the release of melatonin in both diurnal and nocturnal animals. For creatures of the night, however, the hormone signals the time to be active.

81 blue cone photopigments: These are also commonly referred to as “S cone” photopigments. Technically, the photopigments can also detect light into violet range of wavelengths.

82 short wavelengths, around 480 nanometers: Peak sensitivity of melanopsin is generally considered to be approximately 480 nanometers. However, many scientists use other estimates. A slightly longer peak of 490 nanometers, for example, may bet‑ ter account for the natural filtering by the retina in an average adult.

82 emphasis on the color of light: Neitz also argues that most research on the impacts of light on the circadian system use laboratory conditions with 12 hours of steady, diffuse, and white light, followed by 12 hours of darkness. In this situation, the cone input to ipRGCs would be missed.

84 Studies in children: Kevin W. Houser, Lisa Heschong, and Richard Lang, “Buildings, Lighting, and the Myopia Epidemic,” LEUKOS: The Journal of the Illuminating Engineering Society 19, no. 1 (2023): 1–3, doi.org/10.1080/15502724.2022.2141503.

84 skin and retina of rodents: Ethan D. Buhr, Shruti Vemaraju, Nicolás Diaz, Richard A. Lang, and Russell N. Van Gelder. “Neuropsin (OPN5) Mediates Local Light-Dependent Induction of Circadian Clock Genes and Circadian Photoentrainment in Exposed Murine Skin.” Current Biology: CB 29, no. 20 (2019): 3478-3487.e4. doi:10.1016/j.cub.2019.08.063.; Buhr, Ethan D., Wendy W. S. Yue, Xiaozhi Ren, Zheng Jiang, Hsi-Wen Rock Liao, Xue Mei, Shruti Vemaraju, et al. “Neuropsin (OPN5)-Mediated Photoentrainment of Local Circadian Oscillators in Mammalian Retina and Cornea.” Proceedings of the National Academy of Sciences of the United States of America 112, no. 42 (2015): 13093–98. doi:10.1073/pnas.1516259112.

84 defend the skin: As our largest organ and barrier to the outside world, the skin tends to better brace itself against all invaders, including bacteria, viruses, and pollutants during the daytime. At night, the skin becomes more permeable as it repairs and sheds cells. This is also when itching usually intensifies. I can vouch for this; damn those mosquitoes. Mary S. Matsui, Edward Pelle, Kelly Dong, and Nadine Pernodet, “Biological Rhythms in the Skin,” International Journal of Molecular Sciences 17, no. 6 (June 2016): 801, doi:10.3390/ijms17060801.

84 exposing a mouse to ultraviolet light: Shobhan Gaddameedhi et al., “Control of Skin Cancer by the Circadian Rhythm,” Proceedings of the National Academy of Sci- ences of the United States of America 108, no. 46 (September 2011): 18790–95, doi:10.1073/pnas.1115249108; Shobhan Gaddameedhi, Christopher P. Selby, Michael G. Kemp, Rui Ye, and Aziz Sancar, “The Circadian Clock Controls Sunburn Apoptosis and Erythema in Mouse Skin,” The Journal of Investigative Dermatology 135, no. 4 (April 2015): 1119–27, doi:10.1038/jid.2014.508.

85 metabolic activity: Research has even shown that you can change the body temperature of a mouse by simply changing its light environment. “Violet light, body temperature goes down,” said Richard Lang of Cincinnati Children’s. “Blue light, body temperature goes up.”

86 She was a chronobiologist: P. J. de Coursey, “Daily Light Sensitivity Rhythm in a Rodent,” Science 131, no. 3392 (January 1960): 33–35, doi.org/10.1126/science.131.3392.33.

87 strengthen the amplitude: Beatriz Bano-Otalora, Franck Martial, Court Harding, David A. Bechtold, Annette E. Allen, Timothy M. Brown, Mino D. C. Belle, and Robert J. Lucas. “Bright Daytime Light Enhances Circadian Amplitude in a Diurnal Mammal.” Proceedings of the National Academy of Sciences of the United States of America 118, no. 22 (2021). doi:10.1073/pnas.2100094118.

87 The best predictor: Gideon P. Dunster et al., “Daytime Light Exposure Is a Strong Predictor of Seasonal Variation in Sleep and Circadian Timing of University Students,” Journal of Pineal Research 74, no. 2 (March 2023): e12843, doi.org/10.1111/jpi.12843.

91 The first scientific case report: Alfred J. Lewy et al., “Bright Artificial Light Treatment of a Manic‑Depressive Patient with a Seasonal Mood Cycle,” American Journal of Psychiatry 139, no. 11 (November 1982): 1496–98, doi.org/10.1176/ajp.139.11.1496.

91 bright light could suppress melatonin: A. J.Lewy, T. A. Wehr, F. K. Goodwin, D. A. Newsome, and S. P. Markey. “Light Suppresses Melatonin Secretion in Humans.” Science (New York, N.Y.) 210, no. 4475 (1980): 1267–69. doi:10.1126/science.7434030.

92 And Cook was the first: Julian Sancton, Madhouse at the End of the Earth: The Belgica’s Journey into the Dark Antarctic Night (New York: Crown, 2021).

95 same level of melatonin suppression: Andrew J. K. Phillips, Parisa Vidafar, Angus C. Burns, Elise M. McGlashan, Clare Anderson, Shantha M. W. Rajaratnam, Steven W. Lockley, and Sean W. Cain. “High Sensitivity and Interindividual Variability in the Response of the Human Circadian System to Evening Light.” Proceedings of the National Academy of Sciences of the United States of America 116, no. 24 (2019): 12019–24. doi:10.1073/pnas.1901824116.

97 anticipation of those meals: Cheryl M. Isherwood, Daan R. van der Veen, Hana Hassanin, Debra J. Skene, and Jonathan D. Johnston. “Human Glucose Rhythms and Subjective Hunger Anticipate Meal Timing.” Current Biology: CB 33, no. 7 (2023): 1321-1326.e3. doi:10.1016/j.cub.2023.02.005.

97 Also high on the list: Philip Lewis, Horst W. Korf, Liz Kuffer, J. Valérie Groß, and Thomas C. Erren. “Exercise Time Cues (Zeitgebers) for Human Circadian Systems Can Foster Health and Improve Performance: A Systematic Review.” BMJ Open Sport & Exercise Medicine 4, no. 1 (2018): e000443. doi:10.1136/bmjsem-2018-000443.

97 Research has shown that exercise: Dietmar Weinert and Denis Gubin, “The Impact of Physical Activity on the Circadian System: Benefits for Health, Performance and Wellbeing,” Applied Sciences 12, no. 18 (September 2022): 9220, doi.org/10.3390/app12189220; and Ryan A. Martin and Karyn A. Esser, “Time for Exercise? Exer‑ cise and Its Influence on the Skeletal Muscle Clock,” Journal of Biological Rhythms 37, no. 6 (December 2022): 579–92, doi.org/10.1177/07487304221122662.

97 delayed their phase and rise in melatonin: Shawn D. Youngstedt, Jeffrey A. Elliott, and Daniel F. Kripke. “Human Circadian Phase–Response Curves for Exercise.” The Journal of Physiology 597, no. 8 (2019): 2253–68. doi:10.1113/jp276943.

97 Because the Earth’s rotation results: Derk‑Jan Dijk and Anne C. Skeldon, “Human Sleep before the Industrial Era,” Nature 527, no. 7577 (November 2015): 176 –77, doi.org/10.1038/527176a.

97 This internal temperature flux: Ethan D. Buhr, Seung‑Hee Yoo, and Joseph S. Takahashi, “Temperature as a Universal Resetting Cue for Mammalian Circadian Oscillators,” Science 330, no. 6002 (October 2010): 379–85, doi.org/10.1126/science.1195262.

98 The moon’s gravitational pull: C. Helfrich‑Förster et al., “Women Temporarily Synchronize Their Menstrual Cycles with the Luminance and Gravimetric Cycles of the Moon,” Science Advances 7, no. 5 (January 2021): eabe1358, doi.org/10.1126/sciadv.abe1358.

98 Meanwhile, Horacio de la Iglesia: Leandro Casiraghi et al., “Moonstruck Sleep: Synchronization of Human Sleep with the Moon Cycle under Field Condi‑ tions,” Science Advances 7, no. 5 (January 2021): eabe0465, doi.org/10.1126/sciadv. abe0465.

98 The idea that magnetic fields: R. Wever, “The Effects of Electric Fields on Circadian Rhythmicity in Men,” Life Sciences and Space Research 8 (1970): 177–87.

98 Evidence suggests other environmental signals: Musoki Mwimba et al., “Daily Humidity Oscillation Regulates the Circadian Clock to Influence Plant Physiology,” Nature Communications 9 (October 2018): 4290, doi.org/10.1038/s41467‑018‑06692‑2.

98 bird song melodies: Namni Goel. “An Arousing, Musically Enhanced Bird Song Stimulus Mediates Circadian Rhythm Phase Advances in Dim Light.” American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 291, no. 3 (2006): R822-7. doi:10.1152/ajpregu.00550.2005.

CHAPTER 5. dark days

103 Glass windows eventually: Shirin Hirsch and Andrew Smith, “A View through a Window: Social Relations, Material Objects and Locality,” Sociological Review 66, no. 1 (January 2018): 224–40, doi.org/10.1177/0038026117724068.

103 Between 1696 and 1851: Meredith R. Conway, “And You May Ask Yourself, What Is That Beautiful House: How Tax Laws Distort Behavior through the Lens of Archi‑ tecture,” Columbia Journal of Tax Law 10, no. 2 (Summer 2019): 165–97, doi.org/10.7916/cjtl.v10i2.3468.

105 “distorted” property owners’ decisions: Wallace E. Oates and Robert M. Schwab, “The Window Tax: A Case Study in Excess Burden,” Journal of Economic Perspectives 29, no. 1 (Winter 2015): 163–80, doi.org/10.1257/jep.29.1.163.

106 we live our days in constant twilight: Dennis Khodasevich, Susan Tsui, Darwin Keung, Debra J. Skene, Victoria Revell, and Micaela E. Martinez. “Characterizing the Modern Light Environment and Its Influence on Circadian Rhythms.” Proceedings. Biological Sciences 288, no. 1955 (2021): 20210721. doi:10.1098/rspb.2021.0721.

107 Amish community in Lancaster, Pennsylvania: Ellen E. Lee, Ameya Amritwar, L. Elliot Hong, Iqra Mohyuddin, Timothy Brown, and Teodor T. Postolache. “Daily and Seasonal Variation in Light Exposure among the Old Order Amish.” International Journal of Environmental Research and Public Health 17, no. 12 (2020): 4460. doi:10.3390/ijerph17124460.

108 Warnings from the medical community: The Lancet, February 22, 1845, 214–15.

108 biological trickery of ubiquitous artificial light: Marc Hébert, Stacia K. Martin, Clara Lee, and Charmane I. Eastman. “The Effects of Prior Light History on the Suppression of Melatonin by Light in Humans.” Journal of Pineal Research 33, no. 4 (2002): 198–203. doi:10.1034/j.1600-079x.2002.01885.x.; Anne-Marie Chang, Frank A. J. L. Scheer, Charles A. Czeisler, and Daniel Aeschbach. “Direct Effects of Light on Alertness, Vigilance, and the Waking Electroencephalogram in Humans Depend on Prior Light History.” Sleep 36, no. 8 (2013): 1239–46. doi:10.5665/sleep.2894.

109 linked low light during the day: The possibility remains that mental health problems drive unhealthy light and dark exposures. Experts even suggest it might go both ways, causing a vicious cycle as people stay indoors and cut off from natural cycles. Angus C. Burns et al., “Day and Night Light Exposure Are Associated with Psychiatric Disorders: An Objective Light Study in >85,000 People,” Nature Mental Health 1, no. 11 (November 2023): 853–62, doi.org/10.1038/s44220‑023‑00135‑8.

109 animals living with daily shifts: Rohan Nagare, Bernard Possidente, Sarita Lagalwar, and Mariana G. Figueiro, “Robust Light‑Dark Patterns and Reduced Amyloid Load in an Alzheimer’s Disease Transgenic Mouse Model,” Scientific Reports 10, no. 1 (July 2020): 11436, doi.org/10.1038/s41598‑020‑68199‑5.

109 didn’t see enough light: Mariana G. Figueiro, Bryan Steverson, Judith Heerwagen, Kevin Kampschroer, Claudia M. Hunter, Kassandra Gonzales, Barbara Plitnick, and Mark S. Rea. “The Impact of Daytime Light Exposures on Sleep and Mood in Office Workers.” Sleep Health 3, no. 3 (2017): 204–15. doi:10.1016/j.sleh.2017.03.005.

111 In 2022, a team: Timothy M. Brown et al., “Recommendations for Daytime, Evening, and Nighttime Indoor Light Exposure to Best Support Physiology, Sleep, and Wakefulness in Healthy Adults,” PLoS Biology 20, no. 3 (March 2022): e3001571, doi.org/10.1371/journal.pbio.3001571.

115 shadows cover most Manhattan neighborhoods: Quoctrung Bui, and Jeremy White. “Mapping the Shadows of New York City: Every Building, Every Block.” The New York Times. December 21, 2016. https://www.nytimes.com/interactive/2016/12/21/upshot/Mapping-the-Shadows-of-New-York-City.html.

116 snapped a photo: “Billionaire-Building Shadows Creep Across Central Park; ‘Olmsted and Vaux Would Not Be Happy.’” West Side Rag, November 11, 2018.

123 deactivate SARS-CoV-2: Shanna Ratnesar-Shumate, Gregory Williams, Brian Green, Melissa Krause, Brian Holland, Stewart Wood, Jordan Bohannon, et al. “Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces.” The Journal of Infectious Diseases 222, no. 2 (2020): 214–22. doi:10.1093/infdis/jiaa274.

123 Modern science supports her intuition: R. S. Ulrich, “View through a Window May Influence Recovery from Surgery,” Science 224, no. 4647 (April 1984): 420–21,doi.org/10.1126/science.6143402.; Jeffrey M. Walch, Bruce S. Rabin, Richard Day, Jessica N. Williams, Krissy Choi, and James D. Kang. “The Effect of Sunlight on Postoperative Analgesic Medication Use: A Prospective Study of Patients Undergoing Spinal Surgery.” Psychosomatic Medicine 67, no. 1 (2005): 156–63. doi:10.1097/01.psy.0000149258.42508.70.

CHAPTER 6. bright nights

125 live under light-polluted skies: Fabio Falchi, Pierantonio Cinzano, Dan Duriscoe, Christopher C. M. Kyba, Christopher D. Elvidge, Kimberly Baugh, Boris A. Portnov, Nataliya A. Rybnikova, and Riccardo Furgoni. “The New World Atlas of Artificial Night Sky Brightness.” Science Advances 2, no. 6 (2016): e1600377. doi:10.1126/sciadv.1600377.

125 Reflections off asphalt: Researchers found a combination of cloud cover and snow cover increased the nighttime artificial skyglow in a suburb by a factor of 188. An‑ dreas Jechow and Franz Hölker, “Snowglow—the Amplification of Skyglow by Snow and Clouds Can Exceed Full Moon Illuminance in Suburban Areas,” in “Light Pollu‑ tion Assessment with Imaging Devices,” ed. Andreas Jechow, special issue, Journal of Imaging 5, no. 8 (August 2019): 69, doi.org/10.3390/jimaging5080069.

126 That compounds to light pollution: Christopher C. M. Kyba, Yiğit Öner Altıntaş, Constance E. Walker, and Mark Newhouse, “Citizen Scientists Report Global Rapid Reductions in the Visibility of Stars from 2011 to 2022,” Science 379, no. 6629 (January 2023): 265–68, doi.org/10.1126/science.abq7781.

126 That surge in short‑wavelength light: Alejandro Sánchez de Miguel, Jonathan Bennie, Emma Rosenfeld, Simon Dzurjak, and Kevin J. Gaston, “Environmental Risks from Artificial Nighttime Lighting Widespread and Increasing across Eu‑ rope,” Science Advances 8, no. 37 (September 2022): eabl6891, doi.org/10.1126/ sciadv.abl6891.

127 “giant silvery cloud”: Joe Sharkey. “Helping the Stars Take Back the Night.” The New York Times. August 30, 2008. https://www.nytimes.com/2008/08/31/business/31essay.html.

128 nearly one of every two homes: Sean W. Cain et al., “Evening Home Lighting Adversely Impacts the Circadian System and Sleep,” Scientific Reports 10, no. 1 (No‑ vember 2020): 19110, doi.org/10.1038/s41598‑020‑75622‑4.

128 similar conclusions: A selection of these other studies:Diana Paksarian, Kara E. Rudolph, Emma K. Stapp, Gideon P. Dunster, Jianping He, Daniel Mennitt, Samer Hattar, Joan A. Casey, Peter James, and Kathleen R. Merikangas. “Association of Outdoor Artificial Light at Night with Mental Disorders and Sleep Patterns among US Adolescents.” JAMA Psychiatry (Chicago, Ill.) 77, no. 12 (2020): 1266. doi:10.1001/jamapsychiatry.2020.1935.; Maurice M. Ohayon and Cristina Milesi. “Artificial Outdoor Nighttime Lights Associate with Altered Sleep Behavior in the American General Population.” Sleep 39, no. 6 (2016): 1311–20. doi:10.5665/sleep.5860.

128 Artificial light at night has: A sample of this literature: Yong‑Moon Mark Park et al., “Association of Exposure to Artificial Light at Night While Sleeping with Risk of Obesity in Women,” JAMA Internal Medicine 179, no. 8 (August 2019): 1061– 71, doi.org/10.1001/jamainternmed.2019.0571; A. Green et al., “0029 Light Emitted from Media Devices at Night Is Associated with Decline in Sperm Quality,” Sleep 43, no. Supplement_1 (April 2020): A12, doi.org/10.1093/sleep/zsaa056.028; Kenji Obayashi, Keigo Saeki, and Norio Kurumatani. “Bedroom Light Exposure at Night and the Incidence of Depressive Symptoms: A Longitudinal Study of the HEIJO-KYO Cohort.” American Journal of Epidemiology 187, no. 3 (2018): 427–34. doi:10.1093/aje/kwx290.; Ivy C. Mason, Daniela Grimaldi, Kathryn J. Reid, Chloe D. Warlick, Roneil G. Malkani, Sabra M. Abbott, and Phyllis C. Zee. “Light Exposure during Sleep Impairs Cardiometabolic Function.” Proceedings of the National Academy of Sciences of the United States of America 119, no. 12 (2022); Laura M. Argys, Susan L. Averett, and Muzhe Yang. “Light Pollution, Sleep Deprivation, and Infant Health at Birth.” Southern Economic Journal 87, no. 3 (2021): 849–88. doi:10.1002/soej.12477.

129 bacteria in our guts: Chi-Chan Lee, Feng Liang, I-Chi Lee, Tsung-Hao Lu, Yu-Yau Shan, Chih-Fan Jeng, Yan-Fang Zou, Hon-Tsen Yu, and Shih-Kuo Chen (Alen). “External Light‐dark Cycle Shapes Gut Microbiota through Intrinsically Photosensitive Retinal Ganglion Cells.” EMBO Reports 23, no. 6 (2022). doi:10.15252/embr.202052316.

129 rates and severity of COVID‑19 infections: The findings held after researchers accounted for other relevant factors, such as population density and wealth. Amedeo Argentiero, Roy Cerqueti, and Mario Maggi, “Outdoor Light Pollution and COVID‑19: The Italian Case,” Environmental Impact Assessment Review 90 (Septem‑ ber 2021): 106602, doi.org/10.1016/j.eiar.2021.106602; and Yidan Meng, Vincent Zhu, and Yong Zhu, “Co‑distribution of Light at Night (LAN) and COVID‑19 Inci‑ dence in the United States,” BMC Public Health 21 (August 2021), 1509doi.org/10.1186/s12889‑021‑11500‑6.

129 In a separate study: Minjee Kim et al., “Light at Night in Older Age Is Associated with Obesity, Diabetes, and Hypertension,” Sleep 46, no. 3 (March 2023), doi.org/10.1093/sleep/zsac130.

129 comparison might be fitting: William H. Walker II, Jacob R. Bumgarner, James C. Walton, Jennifer A. Liu, O. Hecmarie Meléndez-Fernández, Randy J. Nelson, and A. Courtney DeVries. “Light Pollution and Cancer.” International Journal of Molecular Sciences 21, no. 24 (2020): 9360. doi:10.3390/ijms21249360.

129 Participants who felt like they: Ivy C.Mason et al., “Light Exposure during Sleep Impairs Cardiometabolic Function,” Proceedings of the National Academy of Sciences of the United States of America 119, no. 12 (March 2022): e2113290119, doi.org/10.1073/pnas.2113290119.

129 A study using astronauts’ photos: Ariadna Garcia‑Saenz et al., “Evaluating the Association between Artificial Light‑at‑Night Exposure and Breast and Prostate Cancer Risk in Spain (MCC‑Spain Study),” Environmental Health Perspectives 126, no. 4 (April 2018): 047011, doi.org/10.1289/EHP1837.

129 used satellite images and found: Dong Zhang et al., “Associations between Artificial Light at Night and Risk for Thyroid Cancer: A Large US Cohort Study,” Cancer 127, no. 9 (May 2021): 1448–58, doi.org/10.1002/cncr.33392.

130 Delirium is extremely common: Melissa P. Knauert, Najib T. Ayas, Karen J. Bosma, Xavier Drouot, Mojdeh S. Heavner, Robert L. Owens, Paula L. Watson, et al. “Causes, Consequences, and Treatments of Sleep and Circadian Disruption in the ICU: An Official American Thoracic Society Research Statement.” American Journal of Respiratory and Critical Care Medicine 207, no. 7 (2023): e49–68. doi:10.1164/rccm.202301-0184st.; Jingjing Li, Shining Cai, Xiao Liu, Jinghua Mei, Wenyan Pan, Ming Zhong, and Yuxia Zhang. “Circadian Rhythm Disturbance and Delirium in ICU Patients: A Prospective Cohort Study.” BMC Anesthesiology 23, no. 1 (2023). doi:10.1186/s12871-023-02163-4.

130 lack of light during the day: Hyo Jin Lee, Eunhye Bae, Hong Yeul Lee, Sang-Min Lee, and Jinwoo Lee. “Association of Natural Light Exposure and Delirium According to the Presence or Absence of Windows in the Intensive Care Unit.” Acute and Critical Care 36, no. 4 (2021): 332–41. doi:10.4266/acc.2021.00556.; Hannah J. Durrington, Richard Clark, Ruari Greer, Franck P. Martial, John Blaikley, Paul Dark, Robert J. Lucas, and David W. Ray. “‘In a Dark Place, We Find Ourselves’: Light Intensity in Critical Care Units.” Intensive Care Medicine Experimental 5, no. 1 (2017). doi:10.1186/s40635-017-0122-9.

133 Wildlife also suffers: Annika K. Jägerbrand and Kamiel Spoelstra, “Effects of Anthropogenic Light on Species and Ecosystems,” Science 380, no. 6650 (June 2023): 1125–30, doi.org/10.1126/science.adg3173.

135 squirrel residents: Scott E. Henke, David B. Wester, and Cord B. Eversole. “Holiday Lights Create Light Pollution and Become Ecological Trap for Eastern Fox Squirrels: Case Study on a University Campus.” Human–Wildlife Interactions 16, no. 1 (2022): 12. doi:10.26077/00D4-03EB.

139 In 1990, a federal court: Keenan v. Hall, 83 F.3d 1083 (9th Cir. 1996).

138 And, in 2018: Charles A. Czeisler, “Housing Immigrant Children—the Inhumanity of Constant Illumination,” New England Journal of Medicine 379, no. 2 (July 2018): e3, doi.org/10.1056/NEJMp1808450.

140 People of color and low‑income residents: Shawna M. Nadybal, Timothy W. Collins, and Sara E. Grineski, “Light Pollution Inequities in the Continental United States: A Distributive Environmental Justice Analysis,” Environmental Research 189 (October 2020): 109959, doi.org/10.1016/j.envres.2020.109959.

143 One study found reductions: David Mitre‑Becerril, Sarah Tahamont, Jason Lerner, and Aaron Chalfin, “Can Deterrence Persist? Long‑Term Evidence from a Randomized Experiment in Street Lighting,” Criminology & Public Policy 21, no. 4 (November 2022): 865–91, doi.org/10.1111/1745‑9133.12599.

145 proclamation mandating blackouts and dimouts: “WEST COAST DIMS OUT FOR DURATION OF WAR; Non-Essential Lights on Shore Are Dark, Others Shielded.” The New York Times. August 20, 1942.

146 adopted strict national laws: Martin Morgan‑Taylor, “Regulating Light Pollution: More Than Just the Night Sky,” Science 380, no. 6650 (June 2023): 1118–20, doi.org/10.1126/science.adh7723.

147 core tenets for minimizing light pollution: “Five Principles for Responsible Outdoor Lighting.” Accessed November 20, 2023. https://darksky.org/resources/guides-and-how-tos/lighting-principles/.

149 A 359‑page report: War Department, Control of Coastal Lighting in Anti-submarine Warfare, no. 756 (Fort Belvoir, VA: Engineer Board, April 30, 1943): apps.dtic.mil/sti/pdfs/ADA954894.pdf.

CHAPTER 7. clock scramblers

154 To Hurley’s surprise: Kayla D. Coldsnow, Rick A. Relyea, and Jennifer M. Hurley, “Evolution to Environmental Contamination Ablates the Circadian Clock of an Aquatic Sentinel Species,” Ecology and Evolution 7, no. 23 (December 2017): 10339–49, doi.org/10.1002/ece3.3490.

155 Many traditional contaminants: A few selections from this research: Xiangming Hu et al., “Long‑Term Exposure to Ambient Air Pollution, Circadian Syndrome and Cardiovascular Disease: A Nationwide Study in China,” Science of the Total Environment 868 (April 2023): 161696, doi.org/10.1016/j.scitotenv.2023.161696; and Renate Kopp, Irene Ozáez Martínez, Jessica Legradi, and Juliette Legler, “Expo‑ sure to Endocrine Disrupting Chemicals Perturbs Lipid Metabolism and Circadian Rhythms,” Journal of Environmental Sciences 62 (December 2017): 133–37, doi.org/10.1016/j.jes.2017.10.013; Xuehan Zheng, Kun Zhang, Yanbin Zhao, and Karl Fent. “Environmental Chemicals Affect Circadian Rhythms: An Underexplored Effect Influencing Health and Fitness in Animals and Humans.” Environment International 149, no. 106159 (2021): 106159. doi:10.1016/j.envint.2020.106159.

155 small amounts of bisphenol A: Dinushan Nesan, Kira M. Feighan, Michael C. Antle, and Deborah M. Kurrasch. “Gestational Low-Dose BPA Exposure Impacts Suprachiasmatic Nucleus Neurogenesis and Circadian Activity with Transgenerational Effects.” Science Advances 7, no. 22 (2021): eabd1159. doi:10.1126/sciadv.abd1159.

155 The timing of these exposures: Jacqueline M. Leung and Micaela E. Martinez, “Circadian Rhythms in Environmental Health Sciences,” Current Environmental Health Reports 7, no. 3 (September 2020): 272–81, doi.org/10.1007/s40572‑020‑00285‑2.

157 Caffeine affects both the circadian: Tina M. Burke et al., “Effects of Caffeine on the Human Circadian Clock In Vivo and In Vitro,” Science Translational Medicine 7, no. 305 (September 2015): 305ra146, doi.org/10.1126/scitranslmed.aac5125.

158 circadian clocks in animals who eat a lot of fat can break: Lukasz Chrobok, Jasmin D. Klich, Anna M. Sanetra, Jagoda S. Jeczmien-Lazur, Kamil Pradel, Katarzyna Palus-Chramiec, Mariusz Kepczynski, Hugh D. Piggins, and Marian H. Lewandowski. “Rhythmic Neuronal Activities of the Rat Nucleus of the Solitary Tract Are Impaired by High-Fat Diet – Implications for Daily Control of Satiety.” The Journal of Physiology 600, no. 4 (2022): 751–67. doi:10.1113/JP281838.

159 Half of adults: The average was around 14 hours and 45 minutes. However, that was a conservative measure, as the researchers eliminated the earliest and latest two-and-a-half percent of eating times in their study. Shubhroz Gill and Satchidananda Panda, “A Smartphone App Reveals Erratic Diurnal Eating Patterns in Humans That Can Be Modulated for Health Benefits,” Cell Metabolism 22, no. 5 (November 2015): 789–98, doi.org/10.1016/j.cmet.2015.09.005.

162 Our fat‑burning system: Satchin Panda, The Circadian Code: Lose Weight, Super- charge Your Energy, and Transform Your Health from Morning to Midnight (New York: Rodale, 2018), 192.

164 Mice who ate those unhealthy: Megumi Hatori et al., “Time‑Restricted Feeding without Reducing Caloric Intake Prevents Metabolic Diseases in Mice Fed a High‑Fat Diet,” Cell Metabolism 15, no. 6 (June 2012): 848–60, doi.org/10.1016/j.cmet.2012.04.019.

164 In 2019, researchers from Salk: Michael J. Wilkinson, Emily N. C. Manoogian, Adena Zadourian, Hannah Lo, Savannah Fakhouri, Azarin Shoghi, Xinran Wang, et al., “Ten-Hour Time-Restricted Eating Reduces Weight, Blood Pressure, and Atherogenic Lipids in Patients with Metabolic Syndrome,” Cell Metabolism 31, no. 1 (January 2020): 92–104.e5, doi.org/10.1016/j.cmet.2019.11.004.

164 In studies of mice: Daniel S. Whittaker, Laila Akhmetova, Daniel Carlin, Haylie Romero, David K. Welsh, Christopher S. Colwell, and Paula Desplats, “Circadian Modulation by Time-Restricted Feeding Rescues Brain Pathology and Improves Memory in Mouse Models of Alzheimer’s Disease,” Cell Metabolism 35, no. 10 (October 2023): 1704–1721.e6, doi.org/10.1016/j.cmet.2023.07.014.

164 reduced the beta-amyloid plaques: Daniel S. Whittaker, Laila Akhmetova, Daniel Carlin, Haylie Romero, David K. Welsh, Christopher S. Colwell, and Paula Desplats. “Circadian Modulation by Time-Restricted Feeding Rescues Brain Pathology and Improves Memory in Mouse Models of Alzheimer’s Disease.” Cell Metabolism 35, no. 10 (2023): 1704-1721.e6. doi:10.1016/j.cmet.2023.07.014.

165 After designing and constructing feeders: Victoria Acosta-Rodríguez, Filipa Rijo-Ferreira, Mariko Izumo, Pin Xu, Mary Wight-Carter, Carla B. Green, and Joseph S. Takahashi, “Circadian Alignment of Early Onset Caloric Restriction Promotes Longevity in Male C57BL/6J Mice,” Science 376, no. 6598 (May 2022): 1192–1202, doi.org/10.1126/science.abk0297.

165 decreased the activity of genes involved in inflammatory signaling: Shaunak Deota, Terry Lin, Amandine Chaix, April Williams, Hiep Le, Hugo Calligaro, Ramesh Ramasamy, Ling Huang, and Satchidananda Panda. “Diurnal Transcriptome Landscape of a Multi-Tissue Response to Time-Restricted Feeding in Mammals.” Cell Metabolism 35, no. 1 (2023): 150-165.e4. doi:10.1016/j.cmet.2022.12.006.

166 The findings so far have overthrown the paradigm: Maria M. Mihaylova, Amandine Chaix, Mirela Delibegovic, Jon J. Ramsey, Joseph Bass, Girish Melkani, Rajat Singh, et al., “When a Calorie Is Not Just a Calorie: Diet Quality and Timing as Mediators of Metabolism and Healthy Aging,” Cell Metabolism 35, no. 7 (July 2023): 1114–31, doi.org/10.1016/j.cmet.2023.06.008.

167 the women who ate like queens: Daniela Jakubowicz, Maayan Barnea, Julio Wainstein, and Oren Froy, “High Caloric Intake at Breakfast vs. Dinner Differentially Influences Weight Loss of Overweight and Obese Women,” Obesity 21, no. 12 (December 2013): 2504–12, doi.org/10.1002/oby.20460.

170 circadian system is primed for a meal: Sarah L. Chellappa, Jingyi Qian, Nina Vujovic, Christopher J. Morris, Arlet Nedeltcheva, Hoa Nguyen, Nishath Rahman, et al. “Daytime Eating Prevents Internal Circadian Misalignment and Glucose Intolerance in Night Work.” Science Advances 7, no. 49 (2021): eabg9910. doi:10.1126/sciadv.abg9910.

170 study of firefighters: Emily N. C. Manoogian, Adena Zadourian, Hannah C. Lo, Nikko R. Gutierrez, Azarin Shoghi, Ashley Rosander, Aryana Pazargadi, et al. “Feasibility of Time-Restricted Eating and Impacts on Cardiometabolic Health in 24-h Shift Workers: The Healthy Heroes Randomized Control Trial.” Cell Metabolism 34, no. 10 (2022): 1442-1456.e7. doi:10.1016/j.cmet.2022.08.018.

171 New mothers commonly: Jennifer Hahn-Holbrook, Darby Saxbe, Christine Bixby, Caroline Steele, and Laura Glynn, “Human Milk as ‘Chrononutrition’: Implications for Child Health and Development,” Pediatric Research 85, no. 7 (June 2019): 936–42, doi.org/10.1038/s41390-019-0368-x.

174 When the microbiome is confronted:  Bishehsari, Faraz, Robin M. Voigt, and Ali Keshavarzian. 2020. “Circadian Rhythms and the Gut Microbiota: From the Metabolic Syndrome to Cancer.” Nature Reviews. Endocrinology 16 (12): 731–39. https://doi.org/10.1038/s41574-020-00427-4.

174 shared between mice via fecal transplantation: Christoph A.Thaiss, David Zeevi, Maayan Levy, Gili Zilberman-Schapira, Jotham Suez, Anouk C. Tengeler, Lior Abramson, et al. “Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis.” Cell 159, no. 3 (2014): 514–29. doi:10.1016/j.cell.2014.09.048.

CHAPTER 8. mismatched hours

177 The unfortunate aptness of Boom: If you’re curious, my car’s name was inspired by a group of Seahawks players nicknamed the “Legion of Boom.”

188 slightly greater risks: A selection of the literature: Josef Fritz, Trang VoPham, Kenneth P. Wright Jr, and Céline Vetter. “A Chronobiological Evaluation of the Acute Effects of Daylight Saving Time on Traffic Accident Risk.” Current Biology: CB 30, no. 4 (2020): 729-735.e2. doi:10.1016/j.cub.2019.12.045.; Osborne-Christenson, Eric Jonathon. “Saving Light, Losing Lives: How Daylight Saving Time Impacts Deaths from Suicide and Substance Abuse.” Health Economics 31, no. S2 (2022): 40–68. doi:10.1002/hec.4581.; Liu, Constance, Joseph A. Politch, Evan Cullerton, Kathryn Go, Samuel Pang, and Wendy Kuohung. “Impact of Daylight Savings Time on Spontaneous Pregnancy Loss in in Vitro Fertilization Patients.” Chronobiology International 34, no. 5 (2017): 571–77. doi:10.1080/07420528.2017.1279173.

188 altruistic giving: Eti Ben Simon, Raphael Vallat, Aubrey Rossi, and Matthew P. Walker. “Sleep Loss Leads to the Withdrawal of Human Helping across Individuals, Groups, and Large-Scale Societies.” PLoS Biology 20, no. 8 (2022): e3001733. doi:10.1371/journal.pbio.3001733.

188 judges more liable to dole out longer sentences: Shai Danziger, Jonathan Levav, and Liora Avnaim-Pesso. “Extraneous Factors in Judicial Decisions.” Proceedings of the National Academy of Sciences of the United States of America 108, no. 17 (2011): 6889–92. doi:10.1073/pnas.1018033108.

188 One team of economists estimated: The researchers used a sophisticated statistical method called regression discontinuity design, which allowed them to account for obvious potential confounders such as the presence of high-earning metropolitan areas along the eastern seaboard. Osea Giuntella and Fabrizio Mazzonna, “Sunset Time and the Economic Effects of Social Jetlag: Evidence from US Time Zone Borders,” Journal of Health Economics 65 (May 2019): 210–26, doi.org/10.1016/j.jhealeco.2019.03.007.

188 car accidents are higher: Jeffery Gentry, Jayson Evaniuck, Thanchira Suriyamongkol, and Ivana Mali. “Living in the Wrong Time Zone: Elevated Risk of Traffic Fatalities in Eccentric Time Localities.” Time & Society 31, no. 4 (2022): 457–79. doi:10.1177/0961463×221104675.

190 The sudden change can botch: Thomas Kantermann, Myriam Juda, Martha Merrow, and Till Roenneberg, “The Human Circadian Clock’s Seasonal Adjustment Is Disrupted by Daylight Saving Time,” Current Biology 17, no. 22 (November 2007): 1996–2000, doi.org/10.1016/j.cub.2007.10.025.

190 More than 40 percent: “Why Change?,” Start School Later, accessed November 24, 2023, startschoollater.net/why-change.html.

191 Teenagers’ predilection to stay: Till Roenneberg, Internal Time: Chronotypes, Social Jet Lag, and Why You’re So Tired (Cologne: DuMont Buchverlag, 2012), 102.

192 Starting as early as elementary: Giulia Zerbini, Vincent van der Vinne, Lana K. M. Otto, Thomas Kantermann, Wim P. Krijnen, Till Roenneberg, and Martha Merrow, “Lower School Performance in Late Chronotypes: Underlying Factors and Mechanisms,” Scientific Reports 7 (June 2017): 4385, doi.org/10.1038/s41598-017-04076-y; Talat Arbabi, Christian Vollmer, Tobias Dörfler, and Christoph Randler. “The Influence of Chronotype and Intelligence on Academic Achievement in Primary School Is Mediated by Conscientiousness, Midpoint of Sleep and Motivation.” Chronobiology International 32, no. 3 (2015): 349–57. doi:10.3109/07420528.2014.980508.

192 owls earn lower incomes than larks: Jens Bonke. “Do Morning-Type People Earn More than Evening-Type People? How Chronotypes Influence Income.” Annals of Economics and Statistics, no. 105/106 (2012): 55. doi:10.2307/23646456.

194 Shift workers are also now thought to face: A sample of studies: Li Wang, Qi Ma, Binbin Fang, Yinxia Su, Wanxian Lu, Mengdi Liu, Xue Li, Jiwen Liu, and Lijuan He. “Shift Work Is Associated with an Increased Risk of Type 2 Diabetes and Elevated RBP4 Level: Cross Sectional Analysis from the OHSPIW Cohort Study.” BMC Public Health 23, no. 1 (2023). doi:10.1186/s12889-023-16091-y.; Lauren A. Booker, Tracey L. Sletten, Pasquale K. Alvaro, Maree Barnes, Allison Collins, Ching Li Chai-Coetzer, Aqsa Naqvi, et al. “Exploring the Associations between Shift Work Disorder, Depression, Anxiety and Sick Leave Taken amongst Nurses.” Journal of Sleep Research 29, no. 3 (2020). doi:10.1111/jsr.12872.

194 One study found hospitalized shift: Robert Maidstone, Simon G. Anderson, David W. Ray, Martin K. Rutter, Hannah J. Durrington, and John F. Blaikley, “Shift Work Is Associated with Positive COVID-19 Status in Hospitalised Patients,” Thorax 76, no. 6 (June 2021): 601–6, thorax.bmj.com/content/76/6/601.

195 Still, the conflicting results: Aziz Sancar and Russell N. Van Gelder, “Clocks, Cancer, and Chronochemotherapy,” Science 371, no. 6524 (January 2021): eabb0738, doi.org/10.1126/science.abb0738.

195 Pregnant women working: Danielle A. Clarkson‑Townsend et al., “Maternal Cir‑ cadian Disruption Is Associated with Variation in Placental DNA Methylation,” PloS One 14, no. 4 (2019): e0215745, doi.org/10.1371/journal.pone.0215745.

195 Dad, too, could transfer troubles: Maximilian Lassi et al., “Disruption of Paternal Circadian Rhythm Affects Metabolic Health in Male Offspring via Nongerm Cell Factors,” Science Advances 7, no. 22 (May 2021): eabg6424, doi.org/10.1126/sciadv.abg6424.

CHAPTER 9. goodbye, alarm clock

203 In a photograph taken: Much of Mary Smith’s story, and that of the knocker‑upper profession, is recounted in this paper: Arunima Datta, “Knocker Ups: A Social History of Waking Up in Victorian Britain’s Industrial Towns,” Journal of Victorian Culture 25, no. 3 (July 2020): 331–48, doi.org/10.1093/jvcult/vcaa013.

209 chronotype-adjusted schedules: Céline Vetter, Dorothee Fischer, Joana L. Matera, and Till Roenneberg. “Aligning Work and Circadian Time in Shift Workers Improves Sleep and Reduces Circadian Disruption.” Current Biology: CB 25, no. 7 (2015): 907–11.

211 Younger workers tend: This section leans on an interview with Helen Burgess and her paper: Helen J. Burgess, Katherine M. Sharkey, and Charmane I. Eastman, “Bright Light, Dark and Melatonin Can Promote Circadian Adaptation in Night Shift Work‑ ers,” Sleep Medicine Reviews 6, no. 5 (October 2002): 407–20, doi.org/10.1016/S1087‑0792(01)90215‑1.

212 partially re‑entrained workers: Mark R. Smith, Louis F. Fogg, and Charmane I. Eastman, “A Compromise Circadian Phase Position for Permanent Night Work Im‑ proves Mood, Fatigue, and Performance,” Sleep 32, no. 11 (November 2009): 1481–89, doi.org/10.1093/sleep/32.11.1481.

216 Before‑and‑after data collected: Gideon P. Dunster et al., “Sleepmore in Seattle: Later School Start Times Are Associated with More Sleep and Better Performance in High School Students,” Science Advances 4, no. 12 (December 2018): eaau6200, doi.org/10.1126/sciadv.aau6200.

218 economic and public health boon: “The Economic Benefits of Later School Start Times in the U.S.” Accessed November 20, 2023. https://www.rand.org/randeurope/research/projects/economic-benefits-of-later-school-start-times.html.

221 Or that rates dropped again: Vidya Krishnan and Karin G. Johnson. “Debunking Myths about Daylight Saving Time: Ten Things Everyone Should Know about the Benefits of Permanent Standard Time.” Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine 19, no. 9 (2023): 1573–76. doi:10.5664/jcsm.10666.

223 failed to find an overall energy savings: Kotchen, Matthew, and Laura Grant. “Does Daylight Saving Time Save Energy? Evidence from a Natural Experiment in Indiana.” Cambridge, MA: National Bureau of Economic Research, 2008.; “Does Extending Daylight Saving Time Save Energy? Evidence from an Australian Experiment.” Accessed November 24, 2023. https://www.iza.org/publications/dp/2704/does-extending-daylight-saving-time-save-energy-evidence-from-an-australian-experiment.

224 Again, scientists fervently warn: Till Roenneberg et al., “Why Should We Abolish Daylight Saving Time?,” Journal of Biological Rhythms 34, no. 3 (June 2019): 227– 30, doi.org/10.1177/0748730419854197.

224 David Prerau, author, David Prerau, “Advantages Abound with Changing Clocks Twice a Year,” The Sun (Lowell, MA), March 12, 2023, lowellsun.com/2023/03/12/david‑prerau‑advantages‑abound‑with‑changing‑clocks‑twice‑a‑year.

226 Till Roenneberg and colleagues have: Till Roenneberg, Eva C. Winnebeck, and Elizabeth B. Klerman, “Daylight Saving Time and Artificial Time Zones—a Battle between Biological and Social Times,” Frontiers in Physiology 10 (August 2019): 944, doi.org/10.3389/fphys.2019.00944.

CHAPTER 10. Let there be light, and dark

238 reacted faster and had fewer lapses in attention: Steven W. Lockley, Erin E. Evans, Frank A. J. L. Scheer, George C. Brainard, Charles A. Czeisler, and Daniel Aeschbach. “Short-Wavelength Sensitivity for the Direct Effects of Light on Alertness, Vigilance, and the Waking Electroencephalogram in Humans.” Sleep 29, no. 2 (2006): 161–68. doi:10.1093/sleep/29.2.161.

238 an hour dose of 40-lux blue light: C. Martyn Beaven and Johan Ekström. “A Comparison of Blue Light and Caffeine Effects on Cognitive Function and Alertness in Humans.” PloS One 8, no. 10 (2013): e76707. doi:10.1371/journal.pone.0076707.

238 studies led by Mariana Figueiro: Mariana G. Figueiro et al., “The Impact of Day‑time Light Exposures on Sleep and Mood in Office Workers,” Sleep Health 3, no. 3 (June 2017): 204–15, doi.org/10.1016/j.sleh.2017.03.005.

239 students from preschool through college: Alana Pulay and Amy Williamson. “A Case Study Comparing the Influence of LED and Fluorescent Lighting on Early Childhood Student Engagement in a Classroom Setting.” Learning Environments Research 22, no. 1 (2019): 13–24. doi:10.1007/s10984-018-9263-3.; Leilah K. Grant, Brianne A. Kent, Matthew D. Mayer, Robert Stickgold, Steven W. Lockley, and Shadab A. Rahman. “Daytime Exposure to Short Wavelength-Enriched Light Improves Cognitive Performance in Sleep-Restricted College-Aged Adults.” Frontiers in Neurology 12 (2021): 624217. doi:10.3389/fneur.2021.624217.

239 In a 2023 paper: Martin Moore‑Ede et al., “Lights Should Support Circadian Rhythms: Evidence‑Based Scientific Consensus,” Frontiers in Photonics 4 (2023): 1272934, doi.org/10.3389/fphot.2023.1272934.

240 She described a cautionary case: Food and Drug Administration, “Lamp’s Label‑ ing Found to be Fraudulent,” FDA Talk Paper T86‑69, September 10, 1986, cdn.centerforinquiry.org/wp‑content/uploads/sites/33/2021/03/22170721/vitalite_fraud_notice_1986.pdf.

241 fivefold variation in circadian-stimulating light: Sarah Safranek and Belal Abboushi. “The Impact of Circadian Lighting Design Strategies on Lighting and Cooling Energy of an Office Space.” Office of Scientific and Technical Information (OSTI), 2023.

242 putting light “only where it is useful,”: Morgan Pattison, Monica Hansen, Norman Bardsley, Gregory Thomson, Kelly Gordon, Andrea Wilkerson, Kyung Lee, Valerie Nubbe, and Sean Donnelly. “2022 Solid-State Lighting R&D Opportunities.” Office of Scientific and Technical Information (OSTI), 2022.

247 These small changes combined: Robert Soler and Erica Voss, “Biologically Relevant Lighting: An Industry Perspective,” Frontiers in Neuroscience 15 (2021): 637221, doi.org/10.3389/fnins.2021.637221.

247 Now slightly sleep deprived: Leilah K. Grant et al., “Supplementation of Ambient Lighting with a Task Lamp Improves Daytime Alertness and Cognitive Performance in Sleep‑Restricted Individuals,” Sleep 46, no. 8 (August 2023): zsad096, doi.org/10.1093/sleep/zsad096.

247 Models can now evaluate: John Mardaljevic. “The Implementation of Natural Lighting for Human Health from a Planning Perspective.” Lighting Research & Technology (London, England: 2001) 53, no. 5 (2021): 489–513. doi:10.1177/14771535211022145.

249 premature infants who get cycles of light and dark: Iris Morag and Arne Ohlsson. “Cycled Light in the Intensive Care Unit for Preterm and Low Birth Weight Infants.” Cochrane Database of Systematic Reviews 2020, no. 8 (2016): CD006982. doi:10.1002/14651858.CD006982.pub4.; Samuel Vásquez-Ruiz, José Alfonso Maya-Barrios, Patricia Torres-Narváez, Benito Rubén Vega-Martínez, Adelina Rojas-Granados, Carolina Escobar, and Manuel Angeles-Castellanos. “A Light/Dark Cycle in the NICU Accelerates Body Weight Gain and Shortens Time to Discharge in Preterm Infants.” Early Human Development 90, no. 9 (2014): 535–40. doi:10.1016/j.earlhumdev.2014.04.015.; Esther M. Hazelhoff, Jeroen Dudink, Johanna H. Meijer, and Laura Kervezee. “Beginning to See the Light: Lessons Learned from the Development of the Circadian System for Optimizing Light Conditions in the Neonatal Intensive Care Unit.” Frontiers in Neuroscience 15 (2021): 634034. doi:10.3389/fnins.2021.634034.

250 ipRGCs begin responding to light: Jiaxi Hu, Yiming Shi, Jiaming Zhang, Xinfeng Huang, Qian Wang, Hang Zhao, Jiawei Shen, et al. “Melanopsin Retinal Ganglion Cells Mediate Light-Promoted Brain Development.” Cell 185, no. 17 (2022): 3124-3137.e15. doi:10.1016/j.cell.2022.07.009.

250 linked to the season of birth: Among the studies: Brian K. Lee, Raz Gross, Richard W. Francis, Håkan Karlsson, Diana E. Schendel, Andre Sourander, Abraham Reichenberg, et al. “Birth Seasonality and Risk of Autism Spectrum Disorder.” European Journal of Epidemiology 34, no. 8 (2019): 785–92. doi:10.1007/s10654-019-00506-5.

250 Blue light and violet light could be: D. Van Gilst et al., “Effects of the Neonatal Intensive Care Environment on Circadian Health and Development of Preterm In‑ fants,” Frontiers in Physiology 14 (August 2023): 1243162, doi.org/10.3389/fphys.2023.1243162; James Greenberg, Katherine Gruner, Lousette Rodney, Jaime Struve, Daniel Kang, Yuying Cao, and Richard Lang. “Biologically Aware Lighting for Newborn Intensive Care.” Research Square, 2023. doi:10.21203/rs.3.rs-3120637/v1.

253 seven times the illuminance: P. L. Turner and M. A. Mainster. “Circadian Photoreception: Ageing and the Eye’s Important Role in Systemic Health.” The British Journal of Ophthalmology 92, no. 11 (2008): 1439–44. doi:10.1136/bjo.2008.141747.

253 One study linked cataract removal: Cecilia S. Lee et al., “Association between Cataract Extraction and Development of Dementia,” JAMA Internal Medicine 182, no. 2 (February 2022): 134–41, doi.org/10.1001/jamainternmed.2021.6990.

254 randomly assigning corridors: Rosa Baier, Ellen McCreedy, Naomi J. Miller, Eunice N. Waggoner, Scott Stringer, David R. Gifford, Rebecca Uth, and Terrie F. Wetle. “Impact of Tuned Lighting on Skilled Nursing Center Residents’ Sleep.” Seniors Housing & Care Journal 28, no. 1 (2020). https://www.osti.gov/biblio/1735940.

255 nursing homes in Wisconsin: Leilah K. Grant et al., “Impact of Upgraded Lighting on Falls in Care Home Residents,” Journal of the American Medical Directors As- sociation 23, no. 10 (October 2022): 1698–1704.e2, doi.org/10.1016/j.jamda.2022.06.013.

CHAPTER 11. hacking rhythms

262 Reducing short wavelength light: Christian Cajochen, Sylvia Frey, Doreen Anders, Jakub Späti, Matthias Bues, Achim Pross, Ralph Mager, Anna Wirz-Justice, and Oliver Stefani. “Evening Exposure to a Light-Emitting Diodes (LED)-Backlit Computer Screen Affects Circadian Physiology and Cognitive Performance.” Journal of Applied Physiology (Bethesda, Md.: 1985) 110, no. 5 (2011): 1432–38. doi:10.1152/japplphysiol.00165.2011.; Stéphanie van der Lely, Silvia Frey, Corrado Garbazza, Anna Wirz-Justice, Oskar G. Jenni, Roland Steiner, Stefan Wolf, Christian Cajochen, Vivien Bromundt, and Christina Schmidt. “Blue Blocker Glasses as a Countermeasure for Alerting Effects of Evening Light-Emitting Diode Screen Exposure in Male Teenagers.” The Journal of Adolescent Health: Official Publication of the Society for Adolescent Medicine 56, no. 1 (2015): 113–19. doi:10.1016/j.jadohealth.2014.08.002.

264 She referred me to: “Woman Who Drinks 6 Cups of Coffee Per Day Trying to Cut Down on Blue Light at Bedtime,” The Onion, April 4, 2017, theonion.com/woman‑who‑drinks‑6‑cups‑of‑coffee‑per‑day‑trying‑to‑cut‑1819579770.

266 nudges the circadian system: Deanna M. Minich, Melanie Henning, Catherine Darley, Mona Fahoum, Corey B. Schuler, and James Frame. “Is Melatonin the ‘next Vitamin D’?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements.” Nutrients 14, no. 19 (2022): 3934. doi:10.3390/nu14193934.

267 Mattress companies including: Shahab Haghayegh et al., “Novel Temperature‑Controlled Sleep System to Improve Sleep: A Proof‑of‑Concept Study,” Journal of Sleep Research 31, no. 6 (December 2022): e13662, doi.org/10.1111/jsr.13662.

270 The US Department of Defense reported: Sarah Chabal, Rachel R. Markwald, Evan D. Chinoy, Joseph DeCicco, and Emily Moslener, Personal Light Treatment Devices as a Viable Countermeasure for Submariner Fatigue (Groton, CT: Naval Subma‑ rine Medical Research Laboratory, 2022), apps.dtic.mil/sti/pdfs/AD1166064.pdf.

273 the 2020 Summer Olympics: Due to the COVID-19 pandemic, the games were held in 2021.

275 selecting more night owls: Elise Facer‑Childs and Roland Brandstaetter, “Circadian Phenotype Composition Is a Major Predictor of Diurnal Physical Performance in Teams,” Frontiers in Neurology 6 (October 2015): 208, doi.org/10.3389/fneur.2015.00208.

275 The average peak performance: R. Lok, G. Zerbini, M. C. M. Gordijn, D. G. M. Beersma, and R. A. Hut, “Gold, Silver or Bronze: Circadian Variation Strongly Affects Performance in Olympic Athletes,” Scientific Reports 10 (October 2020): 16088, doi.org/10.1038/s41598‑020‑72573‑8.

278 my visit to Palo Alto: Renske Lok, Marisol Duran, and Jamie M. Zeitzer, “Moving Time Zones in a Flash with Light Therapy during Sleep,” Scientific Reports 13 (Sep‑ tember 2023): 14458, doi.org/10.1038/s41598‑023‑41742‑w.

279 forty-three minutes more sleep per night: Katherine A.Kaplan, Meital Mashash, Rayma Williams, Holly Batchelder, Lolly Starr-Glass, and Jamie M. Zeitzer. “Effect of Light Flashes vs Sham Therapy during Sleep with Adjunct Cognitive Behavioral Therapy on Sleep Quality among Adolescents: A Randomized Clinical Trial.” JAMA Network Open 2, no. 9 (2019): e1911944. doi:10.1001/jamanetworkopen.2019.11944.

280 The aim is to create: Christopher Bettinger, “ADvanced Acclimation and Protec‑ tion Tool for Environmental Readiness (ADAPTER),” Defense Advanced Research Projects Agency, accessed November 24, 2023, https://www.darpa.mil/program/advanced‑acclimation‑and‑protection‑tool‑for‑environmental‑readiness.

CHAPTER 12. circadian medicine

282 accelerate arthritis: Xiaopeng Song, Tianwen Ma, Hailong Hu, Mingchao Zhao, Hui Bai, Xinyu Wang, Lin Liu, et al. “Chronic Circadian Rhythm Disturbance Accelerates Knee Cartilage Degeneration in Rats Accompanied by the Activation of the Canonical Wnt/β-Catenin Signaling Pathway.” Frontiers in Pharmacology 12 (2021): 760988. doi:10.3389/fphar.2021.760988.

282 Morning is apparently also preferred: Daniel H. Pink, When: The Scientific Secrets of Perfect Timing (New York: Riverhead Books, 2018), 54–55.

282 accounting for daily rhythms: A sampling of the literature: Michelle L. Gumz et al., “Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension—2021 NHLBI Workshop Report,” Hypertension 80, no. 3 (March 2023): 503–22, doi.org/10.1161/hypertensionaha.122.19372; Yihao Liu et al., “The Impact of Circadian Rhythms on the Immune Response to Influenza Vaccination in Middle‑Aged and Older Adults (IMPROVE): A Randomised Controlled Trial,” Immunity & Ageing 19, no. 1 (October 2022): 46, doi.org/10.1186/s12979‑022‑00304‑w; and Maurizio Cutolo, “Glucocorticoids and Chronotherapy in Rheumatoid Arthritis,” RMD Open 2, no. 1 (January 2016): e000203, doi.org/10.1136/rmdopen‑2015‑000203.; S. Chan, L. Rowbottom, R. McDonald, G. A. Bjarnason, M. Tsao, C. Danjoux, E. Barnes, et al. “Does the Time of Radiotherapy Affect Treatment Outcomes? A Review of the Literature.” Clinical Oncology (Royal College of Radiologists (Great Britain)) 29, no. 4 (2017): 231–38. doi:10.1016/j.clon.2016.12.005.; Mark J. Burish, Zheng Chen, and Seung-Hee Yoo. “Emerging Relevance of Circadian Rhythms in Headaches and Neuropathic Pain.” Acta Physiologica (Oxford, England) 225, no. 1 (2019). doi:10.1111/apha.13161.; Maurizio Cutolo. “Glucocorticoids and Chronotherapy in Rheumatoid Arthritis.” RMD Open 2, no. 1 (2016): e000203. doi:10.1136/rmdopen-2015-000203.; Sheng-Sheng Ren, Liang-Liang Xu, Peng Wang, Lian Li, Yi-Tao Hu, Ming-Qing Xu, Ming Zhang, et al. “Circadian Rhythms Have Effects on Surgical Outcomes of Liver Transplantation for Patients with Hepatocellular Carcinoma: A Retrospective Analysis of 147 Cases in a Single Center.” Transplantation Proceedings 51, no. 6 (2019): 1913–19. doi:10.1016/j.transproceed.2019.03.033.

283 Levels of circulating tumor: Zoi Diamantopoulou et al., “The Metastatic Spread of Breast Cancer Accelerates during Sleep,” Nature 607, no. 7917 (July 2022): 156– 62, doi.org/10.1038/s41586‑022‑04875‑y.

284 In 1869, Hyde Salter: Hyde Salter, “On the Treatment of Asthma by Belladonna,” The Lancet 93, no. 2370 (January 30, 1869): 152–53, doi.org/10.1016/S0140‑6736(02)65754‑X.

284 More than a century: Frank A. J. L. Scheer et al., “The Endogenous Circadian System Worsens Asthma at Night Independent of Sleep and Other Daily Behavioral or Environmental Cycles,” Proceedings of the National Academy of Sciences of the United States of America 118, no. 37 (2021): e2018486118, doi.org/10.1073/ pnas.2018486118.

285 fluctuating with the seasons: Ludovic S. Mure et al., “Diurnal Transcriptome Atlas of a Primate across Major Neural and Peripheral Tissues,” Science 359, no. 6381 (February 2018): doi.org/10.1126/science.aao0318.

285 a lot of these rhythmic: Marc D. Ruben, David F. Smith, Garret A. FitzGerald, and John B. Hogenesch, “Dosing Time Matters,” Science 365, no. 6453 (August 2019): 547–49, doi.org/10.1126/science.aax7621.; Ray Zhang, Nicholas F. Lahens, Heather I. Ballance, Michael E. Hughes, and John B. Hogenesch. “A Circadian Gene Expression Atlas in Mammals: Implications for Biology and Medicine.” Proceedings of the National Academy of Sciences of the United States of America 111, no. 45 (2014): 16219–24. doi:10.1073/pnas.1408886111.; James C. Walton, William H. Walker II, Jacob R. Bumgarner, O. Hecmarie Meléndez-Fernández, Jennifer A. Liu, Heather L. Hughes, Alexis L. Kaper, and Randy J. Nelson. “Circadian Variation in Efficacy of Medications.” Clinical Pharmacology and Therapeutics 109, no. 6 (2021): 1457–88. doi:10.1002/cpt.2073.

285 Research suggests that the majority: Timed treatments are most relevant for drugs formulated to be short‑acting, or with a half‑life of less than around eight hours.

285 Pertinent to my surgery: H. Al‑Waeli et al., “Chronotherapy of Non‑steroidal Anti‑inflammatory Drugs May Enhance Postoperative Recovery,” Scientific Reports 10 (January 2020): 468, doi.org/10.1038/s41598‑019‑57215‑y..; Zaid Tamimi, Mohammad Abusamak, Haider Al-Waeli, Mohammad Al-Tamimi, Rola Al Habashneh, Mohammad Ghanim, Mohammed Al-Nusair, Qiman Gao, Belinda Nicolau, and Faleh Tamimi. “NSAID Chronotherapy after Impacted Third Molar Extraction: A Randomized Controlled Trial.” Oral and Maxillofacial Surgery 26, no. 4 (2022): 663–72. doi:10.1007/s10006-021-01029-8.

285 when a person with diabetes takes metformin: Henriksson, Emma, Anne-Laure Huber, Erin K. Soto, Anna Kriebs, Megan E. Vaughan, Drew Duglan, Alanna B. Chan, et al. 2017. “The Liver Circadian Clock Modulates Biochemical and Physiological Responses to Metformin.” Journal of Biological Rhythms 32 (4): 345–58. https://doi.org/10.1177/0748730417710348.

286 Researchers discovered that timing mattered: A few examples: Guy Hazan et al., “Biological Rhythms in COVID‑19 Vaccine Effectiveness in an Observational Cohort Study of 1.5 Million Patients,” Journal of Clinical Investigation 133, no. 11 (June 2023): e167339, doi.org/10.1172/jci167339; Candace D. McNaughton et al., “Diurnal Variation in SARS‑CoV‑2 PCR Test Results: Test Accuracy May Vary by Time of Day,” Journal of Biological Rhythms 36, no. 6 (December 2021): 595–601, doi.org/10.1177/07487304211051841; Michael J. McCarthy, “Circadian Rhythm Disruption in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Implications for the Post‑acute Sequelae of COVID‑19,” Brain, Behavior, & Immunity—Health 20 (March 2022): 100412, doi.org/10.1016/j.bbih.2022.100412.

286 jabs with an mRNA vaccine: Researchers found this midday window to be optimal in a large retrospective study of mRNA COVID vaccination. But not all vaccine studies reach the same conclusion. For example, protein antigen vaccines and vaccines against influenza may peak in effectiveness at different times of day. Different biological pathways and different targets likely require different timing.

287 clever things to dodge dangers and acquire food, like telling time: Reece’s team relies on mouse malaria in their research. Because of the pervasiveness of these rhythmic strategies throughout the animal, plant, and pathogen kingdoms, Sarah Reece said, “it would be pretty shocking if this didn’t apply to human malaria.”

288 We now know the microscopic: Filipa Rijo‑Ferreira et al., “The Malaria Parasite Has an Intrinsic Clock,” Science 368, no. 6492 (May 2020): 746–53, doi.org/10.1126/science.aba2658.

288 entrain that rhythm to their host: Kimberley F.Prior, Filipa Rijo-Ferreira, Patricia A. Assis, Isabella C. Hirako, David R. Weaver, Ricardo T. Gazzinelli, and Sarah E. Reece. “Periodic Parasites and Daily Host Rhythms.” Cell Host & Microbe 27, no. 2 (2020): 176–87. doi:10.1016/j.chom.2020.01.005.

290 rhythms dysregulate and dampen: Yanyan Xu, Shaoyong Su, Xinyue Li, Asifhusen Mansuri, William V. McCall, and Xiaoling Wang. “Blunted Rest-Activity Circadian Rhythm Increases the Risk of All-Cause, Cardiovascular Disease and Cancer Mortality in US Adults.” Scientific Reports 12, no. 1 (2022): 20665. doi:10.1038/s41598-022-24894-z.

291 Circadian rhythm disruption and neurodegeneration: Erik S. Musiek, David D. Xiong, and David M. Holtzman, “Sleep, Circadian Rhythms, and the Pathogene‑ sis of Alzheimer Disease,” Experimental & Molecular Medicine 47, no. 3 (March 2015): e148, doi.org/10.1038/emm.2014.121.; Gretchen T.Clark, Yanlei Yu, Cooper A. Urban, Guo Fu, Chunyu Wang, Fuming Zhang, Robert J. Linhardt, and Jennifer M. Hurley. “Circadian Control of Heparan Sulfate Levels Times Phagocytosis of Amyloid Beta Aggregates.” PLoS Genetics 18, no. 2 (2022): e1009994. doi:10.1371/journal.pgen.1009994.

292 Research suggests that daytime: Nathaniel P. Hoyle et al., “Circadian Actin Dynamics Drive Rhythmic Fibroblast Mobilization during Wound Healing,” Science Translational Medicine 9, no. 415 (November 2017): doi.org/10.1126/scitranslmed.aal2774.

293 His data collected from neurons: Kayla E. Rohr and Michael J. McCarthy, “The Impact of Lithium on Circadian Rhythms and Implications for Bipolar Disorder Pharmacotherapy,” Neuroscience Letters 786 (August 2022): 136772, doi.org/10.1016/j.neulet.2022.136772.

294 This discovery has led: Zhen Dong et al., “Targeting Glioblastoma Stem Cells through Disruption of the Circadian Clock,” Cancer Discovery 9, no. 11 (November 2019): 1556–73, doi.org/10.1158/2159‑8290.CD‑19‑0215.

295 They tested their theory: Anna R. Damato et al., “Temozolomide Chronotherapy in Patients with Glioblastoma: A Retrospective Single‑Institute Study,” Neurooncology Advances 3, no. 1 (January–December 2021): vdab041, doi.org/10.1093/noajnl/vdab041.

295 Medical schools pay scant: Julia M. Selfridge, Kurtis Moyer, Daniel G. S. Capel‑ luto, and Carla V. Finkielstein, “Opening the Debate: How to Fulfill the Need for Physicians’ Training in Circadian‑Related Topics in a Full Medical School Curricu‑ lum,” Journal of Circadian Rhythms 13 (November 2015): 7, doi.org/10.5334/jcr.ah.

296 Lo decided to dig: Elga Esposito et al., “Potential Circadian Effects on Translational Failure for Neuroprotection,” Nature 582, no. 7812 (June 2020): 395–98, doi.org/10.1038/s41586‑020‑2348‑z.

298 In one analysis of drug: Marc D. Ruben et al., “A Large‑Scale Study Reveals 24‑h Operational Rhythms in Hospital Treatment,” Proceedings of the National Academy of Sciences of the United States of America 116, no. 42 (October 2019): 20953–58, doi.org/10.1073/pnas.1909557116.

299 Carole Godain remembers: Lynne Peeples, “Medicine’s Secret Ingredient—It’s in the Timing.” Nature 556, no. 7701 (2018): 290–92. doi:10.1038/d41586‑018‑04600‑8. Further correspondence with Godain in 2023.

299 Lévi, also a chronobiologist: Francis Lévi, Rachid Zidani, and Jean‑Louis Misset, “Randomised Multicentre Trial of Chronotherapy with Oxaliplatin, Fluorouracil, and Folinic Acid in Metastatic Colorectal Cancer,” The Lancet 350, no. 9079 (Sep‑ tember 1997): 681–86, doi.org/10.1016/S0140‑6736(97)03358‑8.

300 broken down by sex: Sylvie Giacchetti, Georg Bjarnason, Carlo Garufi, Dominique Genet, Stefano Iacobelli, Marco Tampellini, Rune Smaaland, et al. “Phase III Trial Comparing 4-Day Chronomodulated Therapy versus 2-Day Conventional Delivery of Fluorouracil, Leucovorin, and Oxaliplatin as First-Line Chemotherapy of Metastatic Colorectal Cancer: The European Organisation for Research and Treatment of Cancer Chronotherapy Group.” Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology 24, no. 22 (2006): 3562–69. doi:10.1200/jco.2006.06.1440.

300 in women: Lévi showed that a colorectal drug was least toxic for men at the time it was most toxic for women: 9 a.m. Women tolerated the drug best between 1 p.m. and 5 p.m. Pasquale F. Innominato, Annabelle Ballesta, Qi Huang, Christian Focan, Philippe Chollet, Abdoulaye Karaboué, Sylvie Giacchetti, et al. “Sex‐dependent Least Toxic Timing of Irinotecan Combined with Chronomodulated Chemotherapy for Metastatic Colorectal Cancer: Randomized Multicenter EORTC 05011 Trial.” Cancer Medicine 9, no. 12 (2020): 4148–59. doi:10.1002/cam4.3056.

302 predict things: Azure Grant and Benjamin Smarr. “Feasibility of Continuous Distal Body Temperature for Passive, Early Pregnancy Detection.” PLOS Digital Health 1, no. 5 (2022): e0000034. doi:10.1371/journal.pdig.0000034.

CHAPTER 13. extended hours

304 Of course, life on Mars: Rujia Luo, Yutao Huang, Huan Ma, and Jinhu Guo, “How to Live on Mars with a Proper Circadian Clock?,” Frontiers in Astronomy and Space Sciences 8 (January 2022): 796943, doi.org/10.3389/fspas.2021.796943.

307 harness and hack the clocks: The following section leans on lessons from several researchers, including Alex Webb (University of Cambridge), Joanna Chiu (University of California, Davis), Mark Rea (Mount Sinai), David Gadoury (Cornell University), Jose Pruneda‑Paz (University of California, San Diego), Kath‑ leen Greenham (University of Minnesota), Carlos Hotta (University of São Paulo), and Antony Dodd (John Innes Centre). A couple of in‑depth review papers on the subject: Gareth Steed, Dora Cano Ramirez, Matthew A. Hannah, and Alex A. R. Webb, “Chronoculture, Harnessing the Circadian Clock to Improve Crop Yield and Sustainability,” Science 372, no. 6541 (April 2021): eabc9141, doi.org/10.1126/sci‑ ence.abc9141; and Carlos Takeshi Hotta, “From Crops to Shops: How Agriculture Can Use Circadian Clocks,” Journal of Experimental Botany 72, no. 22 (December 2021): 7668–79, doi.org/10.1093/jxb/erab371.

308 The political geography: Santiago Mora‑ García and Marcelo J. Yanovsky, “A Large Deletion within the Clock Gene LNK2 Contributed to the Spread of Tomato Cultivation from Central America to Europe,” Proceedings of the National Academy of Sciences of the United States of America 115, no. 27 (June 2018): 6888–90, doi.org/10.1073/pnas.1808194115.

311 But if you artificially place: Danielle Goodspeed et al., “Arabidopsis Synchronizes Jasmonate‑Mediated Defense with Insect Circadian Behavior,” Proceedings of the National Academy of Sciences of the United States of America 109, no. 12 (February 2012): 4674–77, doi.org/10.1073/pnas.1116368109.

312 farmers need to spray: Fiona E. Belbin et al., “Plant Circadian Rhythms Regulate the Effectiveness of a Glyphosate‑Based Herbicide,” Nature Communications 10 (Au‑ gust 2019): 3704, doi.org/10.1038/s41467‑019‑11709‑5.

312 Reducing application of Roundup: Who.int, “IARC Monographs Volume 112: Evaluation of Five Organophosphate Insecticides and Herbicides,” accessed Febru‑ ary 5, 2024, https://www.iarc.who.int/news‑events/iarc‑monographs‑volume‑112‑evaluation‑of‑five‑organophosphate‑insecticides‑and‑herbicides.

315 The clock can keep ticking: John D. Liu et al., “Keeping the Rhythm: Light/Dark Cycles during Postharvest Storage Preserve the Tissue Integrity and Nutritional Content of Leafy Plants,” BMC Plant Biology 15 (March 2015): 92, doi.org/10.1186/s12870‑015‑0474‑9.

316 kept under constant environmental conditions: Danielle Goodspeed, John D. Liu, E. Wassim Chehab, Zhengji Sheng, Marta Francisco, Daniel J. Kliebenstein, and Janet Braam. “Postharvest Circadian Entrainment Enhances Crop Pest Resistance and Phytochemical Cycling.” Current Biology: CB 23, no. 13 (2013): 1235–41. doi:10.1016/j.cub.2013.05.034.

318 bolstering beer fermentation: Zheng Eelderink-Chen, Jasper Bosman, Francesca Sartor, Antony N. Dodd, Ákos T. Kovács, and Martha Merrow. “A Circadian Clock in a Nonphotosynthetic Prokaryote.” Science Advances 7, no. 2 (2021): eabe2086. doi:10.1126/sciadv.abe2086.

319 maximally harvest food: Matteo Camporese and Majdi Abou Najm, “Not All Light Spectra Were Created Equal: Can We Harvest Light for Optimum Food‑Energy Co‑ generation?,” Earth’s Future 10, no. 12 (December 2022): e2022EF002900, doi.org/10.1029/2022EF002900.