28.   Matthew Walker, Why We Sleep (New York: Scribner, 2017).

  29.   Tarja Porkka-Heiskanen et al., “Adenosine: A Mediator of the Sleep-Inducing Effects of Prolonged Wakefulness,” Science 276 (1997): 1265–68.

  30.   “New Clues to Why We Snooze,” Science, May 22, 1997, https://www.science.org/content/article/new-clues-why-we-snooze.

  31.   Robert E. Strecker et al., “Another Chapter in the Adenosine story,” Sleep 29 (2006): 426–28.

  32.   Jamie M. Zeitzer et al., “Extracellular Adenosine in the Human Brain During Sleep and Sleep Deprivation: An In Vivo Microdialysis Study,” Sleep 29:455–61 (2006).

  33.   J. V. Retey et al., “A Functional Genetic Variation of Adenosine Deaminase Affects the Duration and Intensity of Deep Sleep in Humans,” Proceedings of the National Academy of Sciences 102 (2005): 15676–81.

  34.   Valerie Bachmann et al., “Functional ADA Polymorphism Increases Sleep Depth and Reduces Vigilant Attention in Humans,” Cerebral Cortex 22 (2012): 962–70.

  35.   Theresa E. Bjorness et al., “Control and Function of the Homeostatic Sleep Response by Adenosine A1 Receptors,” Journal of Neuroscience 29 (2009): 1267–76.

  36.   Ehsan Shokri-Kojori et al., “β-Amyloid Accumulation in the Human Brain After One Night of Sleep Deprivation,” Proceedings of the National Academy of Sciences 115:4483–88 (2018).

  37.   David Elmenhorst et al., “Recovery Sleep After Extended Wakefulness Restores Elevated A1 Adenosine Receptor Availability in the Human Brain,” Proceedings of the National Academy of Sciences 114 (2017): 4243–48.

  38.   Hirofumi Toda et al., “A Sleep-Inducing Gene, nemuri, Links Sleep and Immune Function in Drosophila,” Science 363 (2019): 509–15.

  39.   Daniel A. Lee et al., “Genetic and Neuronal Regulation of Sleep by Neuropeptide VF,” eLife 6 (2017): e25727.

  40.   Hiromasa Funato et al., “Forward Genetic Analysis of Sleep in Randomly Mutagenized Mice,” Nature 539 (2016): 378–83.

  41.   Zhiqiang Wang et al., “Quantitative Phosphoproteomic Analysis of the Molecular Substrates of Sleep Need,” Nature 558 (2018): 435–39.

  42.   Takato Honda et al., “A Single Phosphorylation Site of SIK3 Regulates Daily Sleep Amounts and Sleep Need in Mice,” Proceedings of the National Academy of Sciences 115 (2018): 10458–63.

  43.   Zachary Zamore and Sigrid C. Veasey, “Neural Consequences of Chronic Sleep Disruption,” Trends in Neurosciences 45 (2022): 678–91.

  44.   David Zada et al., “Parp1 Promotes Sleep, Which Enhances DNA Repair in Neurons,” Molecular Cell 81 (2021): 4979–93.

  7. MY FAVORITE MISTAKE

    1.   Andria Simmons, “Keeper of Loud Dogs Gets His Day in Court,” Atlanta Journal Constitution, August 29, 2008.

    2.   Joel M. Geiderman, “Central Nervous System Disturbances Following Clarithromycin Ingestion,” Clinical Infectious Diseases 29 (1999): 464–65.

    3.   Paul S. Garcia and Andrew Jenkins, “Inhibition of the GABA(A) Receptor by a Macrolide but Not by a Lincosamide Antibiotic,” American Society of Anesthesiologists 2009 meeting, A1385, http://www.asaabstracts.com/strands/asaabstracts/abstract.htm?year=2009&index=10&absnum=477.

    4.   Lynn M. Trotti et al., “Improvement in Daytime Sleepiness with Clarithromycin in Patients with GABA-Related Hypersomnia: Clinical Experience,” Journal of Psychopharmacology 28 (2014): 697–702.

    5.   Christian M. Jespersen et al., “Randomised Placebo Controlled Multicentre Trial to Assess Short Term Clarithromycin for Patients with Stable Coronary Heart Disease,” BMJ 332 (2006): 22–27.

    6.   Cory Acuff, November 20, 2008, Office of Technology Transfer “Breakfast Club” presentation.

    7.   The raw numbers were posted on https://www.clinicaltrials.gov/ct2/show/NCT01183312 in 2017.

    8.   Lynn M. Trotti, Lorne A. Becker, and Cochrane Movement Disorders Group, “Iron for the Treatment of Restless Legs Syndrome,” Cochrane Database of Systematic Reviews (2019), CD007834; Lynn M. Trotti et al., “Medications for Daytime Sleepiness in Individuals with Idiopathic Hypersomnia,” Cochrane Database of Systematic Reviews (2021), CD012714.

    9.   Catherine A. Hosmer, Taking the Pulse of the U.S. Health Care System (iUniverse, 2007).

  10.   October 2018 Emory Radiology grand rounds.

  11.   Interviews with Anna’s parents and Saraiah Naps.

  12.   Gabe Gutierrez, “Disorder Causes Lawyer to Sleep up to 18 Hours a Day,” Today/MSNBC, November 25, 2012.

  13.   Melinda Beck, “Scientists Try to Unravel the Riddle of Too Much Sleep,” Wall Street Journal, December 10, 2012.

  14.   Interview with Betsy Ashcraft.

  15.   Gene J. Koprowski, “ ‘Sleeping Beauty’ Gene Proves Beastly for Sufferers,” Fox News, November 21, 2012.

  16.   Greg Miller, “Putting Themselves to Sleep,” Science, November 21, 2012.

  17.   Aisha Tyler, “Sleeping Beauty Syndrome Makes It Hard to Wake Up,” WCSC, https://www.live5news.com/story/29629513/sleeping-beauty-syndrome-makes-it-hard-to-wake-up/.

  18.   Johannes A. Romijn, “Pituitary Diseases and Sleep Disorders,” Current Opinion in Endocrinology, Diabetes and Obesity 23 (2016): 345–51.

  8. THE ATLANTA SLEEPERS CLUB

    1.   Living with Hypersomnia website, archived in 2014: http://web.archive.org/web/20140607062515/http://www.livingwithhypersomnia.com/fr/podcast-001-hypersomnia-conference/.

    2.   Lynn M. Trotti, Beth A. Staab, and David B Rye, “Test-Retest Reliability of the Multiple Sleep Latency Test in Narcolepsy Without Cataplexy and Idiopathic Hypersomnia,” Journal of Clinical Sleep Medicine 9 (2013): 789–95.

    3.   David B. Rye, “What’s in a Name? Understanding the Origins of the Terminologies for the Family of Hypersomnias,” YouTube, Hypersomnia Foundation video posted February 25, 2015, https://youtu.be/qUB1NquAxCI. Rye enthuses over Gowers’s term “somnosis” but does not discuss Bedřich Roth extensively.

    4.   Virginia Hughes, “Wake No More,” Matter, January 26, 2015, https://medium.com/matter/wake-no-more-8bbd49528b9.

    5.   Jackie Sturt et al., “Neurolinguistic Programming: A Systematic Review of the Effects on Health Outcomes,” British Journal of General Practice 62 (2012): e757–e764.

    6.   Archived at http://web.archive.org/web/20120217090029/http://www.confidentfuture.com.au/.

    7.   Lloyd Johnson, “NLP—The Secrets to Learning Neuro-Linguistic Programming Online,” learnNLPonline YouTube video posted May 27, 2012, https://www.youtube.com/watch?v=9DwP62Xrt_k.

    8.   Christian Guilleminault and Susanna Mondini, “Mononucleosis and Chronic Daytime Sleepiness. A Long-Term Follow-Up Study,” Archives of Internal Medicine 146 (1986): 1333–35.

    9.   Erin Kelty et al., “Use of Subcutaneous Flumazenil Preparations for the Treatment of Idiopathic Hypersomnia: A Case Report,” Journal of Psychopharmacology 28 (2014): 703–6.

  10.   National Institutes of Health website archived in 2013: http://web.archive.org/web/20130128095235/http://rarediseases.info.nih.gov/RareDiseaseList.aspx?StartsWith=I. An entry for idiopathic hypersomnolence was added by the end of 2013.

  11.   Mayo Clinic website accessed via http://web.archive.org for 2013–2016.

  12.   Talk About Sleep, archived in 2010, http://web.archive.org/web/20100204051157/http://www.talkaboutsleep.com/idiopathic-hypersomnia/.

  13.   Analysis of comments to FDA Docket 2013-N-0815, obtained by Freedom of Information Act.

  14.   Twitter/email conversations with Chadwick. Also Eva Lewicki, “Aussie Mum’s Medical Mystery,” That’s Life!, May 9, 2020, https://www.thatslife.com.au/aussie-mums-medical-mystery-help-i-cant-stop-sleeping.

  15.   Gary Hulse et al., “Withdrawal and Psychological Sequelae, and Patient Satisfaction Associated with Subcutaneous Flumazenil Infusion for the Management of Benzodiazepine Withdrawal,” Journal of Psychopharmacology 27 (2013): 222–27.

  16.   Sujata Gupta, “Blocking the High: One Man’s Quixotic Quest to Cure Addiction,” Mosaic Science, March 17, 2015, https://mosaicscience.com/story/blocking-the-high/.

  17.   Stefano Tamburin et al., “Low Risk of Seizures with Slow Flumazenil Infusion and Routine Anticonvulsant Prophylaxis for High-Dose Benzodiazepine Dependence,” Journal of Psychopharmacology 31 (2017): 1369–73.

  18.   Gary Hulse et al., “Novel Indications for Benzodiazepine Antagonist Flumazenil in GABA Mediated Pathological Conditions of the Central Nervous System,” Current Pharmaceutical Design 21 (2015): 3325–42.

  19.   Hughes, “Wake No More,” last paragraph.

  20.   Samantha Bresnahan, “Living with Hypersomnia: The Woman Who Slept, but Got No Rest,” CNN, April 22, 2015, https://www.cnn.com/2015/04/22/health/hypersomnia-woman-always-tired/index.html.

  21.   Lynn M. Trotti et al., “Clarithromycin in γ-Aminobutyric Acid–Related Hypersomnolence: A Randomized, Crossover Trial,” Annals of Neurology 78 (2015): 454–65.

  22.   Vincent LaBarbera et al., “Central Disorders of Hypersomnolence, Restless Legs Syndrome and Surgery with General Anesthesia: Patient Perceptions,” Frontiers in Human Neuroscience 12 (2018): 99.

  23.   Emails from Kristin Loomis, executive director of the Human Herpesvirus-6 Foundation.

  24.   ProPublica Nonprofit Explorer, Hypersomnia Foundation, https://projects.propublica.org/nonprofits/organizations/464162735. Also Hypersomnia Foundation Inc. (14019717) documents, downloaded from the Georgia Secretary of State website.

  25.   Hypersomnia Foundation announcement, “Passing the Torch,” January 16, 2017, https://www.hypersomniafoundation.org/passing-the-torch/.

  26.   Page-Rye stepped down from the board in late 2019.

  27.   Susannah L. Rose, “Patient Advocacy Organizations: Institutional Conflicts of Interest, Trust, and Trustworthiness,” Journal of Law, Medicine & Ethics 41 (2013): 680–87.

  28.   Christine Miserandino, “The Spoon Theory,” But You Don’t Look Sick, 2003, https://butyoudontlooksick.com/articles/written-by-christine/the-spoon-theory/.

  9. THE STORY OF FLUMAZENIL

    1.   Willy Haefely and Walter Hunkeler, “The Story of Flumazenil,” European Journal of Anaesthesiology 2S (1988): 3–13.

    2.   Andrea Tone, The Age of Anxiety (New York: Basic Books, 2008).

    3.   “Valium Patent Expires, but Generic Equivalent Still Months Away,” Associated Press, March 2, 1985; “Stay Calm,” Economist, September 28, 1991.

    4.   U.S. Senate, Subcommittee on Health and Scientific Research, “Use and Misuse of Benzodiazepines,” 96th Congress, September 10, 1979 (Washington, DC: U.S. Gov’t Printing Office, 1980).

    5.   Hans C. Peyer, “Roche, a Company History 1896–1996” (Editiones Roche, 1996).

    6.   Hanns Möhler and Mose Da Prada, “The Challenge of Neuropharmacology: A Tribute to the Memory of Willy Haefely” (Editiones Roche, 1994), 9.

    7.   Willy Haefely et al., “Possible Involvement of GABA in the Central Actions of Benzodiazepines,” Advances in Biochemistry and Psychopharmacology 14 (1975): 131–51.

    8.   Hanns Möhler and Toshikazu Okada, “Benzodiazepine Receptor: Demonstration in the Central Nervous System,” Science 198 (1977): 849–51.

    9.   Walter Hunkeler et al., “Selective Antagonists of Benzodiazepines,” Nature 290 (1981): 514–16.

  10.   Hanns Möhler and J. G. Richards, “Agonist and Antagonist Benzodiazepine Receptor Interaction in vitro,” Nature 294 (1981): 763–65.

  11.   “Ein Benzodiazepin, das die Wirkung von Benzodiazepinen aufhebt,” Roche 14 (1982): 11–17. Original quote: “Ich bin über die Versuchsituation voll orientiert, fühle mich wie vom Wecker aus dem Schlaf gerissen und möchte aufstehen.”

  12.   Austin Darragh et al., “Reversal of Benzodiazepine-Induced Sedation by Intravenous Ro 15-1788,” Lancet 318 (1981): 1042.

  13.   Austin Darragh et al., “Absence of Central Effects in Man of the Benzodiazepine Antagonist Ro 15-1788,” Psychopharmacology 80 (1983): 192–95.

  14.   Leslie Iversen, “Anti-Anxiety Receptors in the Brain?,” Nature 266 (1977): 678.

  15.   Solomon Snyder , Brainstorming: The Science and Politics of Opiate Research (Cambridge, MA: Harvard University Press, 1989).

  16.   Walter E. Müller, The Benzodiazepine Receptor (Cambridge: Cambridge University Press, 1987), 78.

  17.   Willy Haefely, “Alleviation of Anxiety: The Benzodiazepine Saga,” in Discoveries in Pharmacology: Psycho-and Neuro-pharmacology, ed. M. J. Parnham and J. Bruinvels (Amsterdam: Elsevier, 1983), 293.

  18.   Jeff Goldberg, Anatomy of a Scientific Discovery (New York: Bantam, 1988), 141–59.

  19.   Giuseppe Scollo-Lavizzari, “The Clinical Anti-Convulsant Effects of Flumazenil, a Benzodiazepine Antagonist,” European Journal of Anesthesiology 2S (1998): 129–38.

  20.   Anna Higgitt, Malcolm Lader, and Peter Fonagy, “The Effects of the Benzodiazepine Antagonist Ro 15-1788 on Psychophysiological Performance and Subjective Measures in Normal Subjects,” Psychopharmacology 89 (1986): 395–403.

  21.   Möhler and Da Prada, “The Challenge of Neuropharmacology,” 125–29.

  22.   Peretz Lavie, “Ro 15-1788 Decreases Hypnotic Effects of Sleep Deprivation,” Life Sciences 41 (1987): 227–33; Peretz Lavie, “Intrinsic Effects of the Benzodiazepine Receptor Antagonist Ro 15-1788 in Sleepy and Alert Subjects,” International Journal of Neuroscience 46 (1989): 131–37.

  23.   H. M. Emrich, P. Sonderegger, and N. Mai, “Action of the Benzodiazepine Antagonist Ro 15-1788 in Humans After Sleep Withdrawal, Neuroscience Letters 47 (1984): 369–73; Axel Steiger et al., “Flumazenil Exerts Intrinsic Activity on Sleep EEG and Nocturnal Hormone Secretion in Normal Controls,” Psychopharmacology 113 (1994): 334–38; Erich Seifritz et al., “Effects of Flumazenil on Recovery Sleep and Hormonal Secretion After Sleep Deprivation in Male Controls,” Psychopharmacology 120 (1995): 449–56; Ulrich Hemmeter et al., “Effect of Flumazenil Augmentation on Microsleep and Mood in Depressed Patients During Partial Sleep Deprivation,” Journal of Psychiatric Research 41 (2007): 876–84.

  24.   David J. Nutt et al., “Flumazenil Provocation of Panic Attacks. Evidence for Altered Benzodiazepine Receptor Sensitivity in Panic Disorder,” Archives of General Psychiatry 47 (1990): 917–25.

  25.   Thaddeus J. Marczynski, J. Artwohl, and B. Marczynska, “Chronic Administration of Flumazenil Increases Life Span and Protects Rats from Age-Related Loss of Cognitive Functions,” Neurobiology of Aging 15 (1994): 69–84.

  26.   Jamie Talan, “Help for AIDS, Alcoholism, Memory?,” Newsday, March 30, 1993.

  27.   John Travis, “Biologists Visit New Orleans (Under an Assumed Name),” Science 260 (1993): 162–63.

  28.   Nick Neave et al., “Dose-dependent Effects of Flumazenil on Cognition, Mood, and Cardio-respiratory Physiology in Healthy Volunteers,” British Dental Journal 189 (2000): 668–74.

  29.   Zoya Farzampour, Richard J. Reimer, and John Huguenard, “Endozepines,” Advances in Pharmacology 72 (2015): 147–64.

  30.   Erminio Costa, An Early Attempt to Foster Neuroscience Globalization (Good Life, 2003); Robert Kanigel, Apprentice to Genius: The Making of a Scientific Dynasty (Baltimore, MD: Johns Hopkins University Press, 1993).

  31.   Alan P. Kozikowski, “On the Path from Chemistry to Neuroscience: Early Explorations in Chemical Medicine Under the Mentorship of Dr. Erminio Costa, a Neuroscientist with a Big Brain and a Bigger Heart,” Pharmacological Research 64 (2011): 327–29.

  32.   Pamela Taulbee, “Solving the Mystery of Anxiety,” Science News 124 (1983): 45.

  33.   Erminio Costa et al., “Pharmacology of Neurosteroid Biosynthesis,” Annals of the New York Academy of Sciences 746 (1994): 223–42.

  34.   Maria D. Majewska et al., “Steroid Hormone Metabolites Are Barbiturate-Like Modulators of the GABA Receptor,” Science 232 (1986): 1004–7.

  35.   Graziano Pinna, “Allopregnanolone, the Neuromodulator Turned Therapeutic Agent: Thank You, Next?,” Frontiers in Endocrinology 11 (2020).

  36.   Johanna Berthier et al., “Menstruation-Related Hypersomnia: Three Adolescent Cases Responding to Treatment with the Oral Contraceptive Pill,” Journal of Neuroscience and Neuropsychology 3 (2019): 102.