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Published in final edited form as: Sleep Health. 2024 Feb 7;10(1 Suppl):S4–S10. doi: 10.1016/j.sleh.2024.01.003

A Perspective on the Festschrift of Charles A. Czeisler PhD MD

Elizabeth B Klerman a,b,c, Kenneth P Wright Jr d, Jeanne F Duffy b,c, Frank AJL Scheer b,c, Anne-Marie Chang e, Charles A Czeisler b,c, Shantha MW Rajaratnam b,c,f
PMCID: PMC11031332  NIHMSID: NIHMS1968081  PMID: 38331654

Opportunity (by EB Klerman and SMW Rajaratnam)

Dr. Charles Andrew Czeisler views situations as opportunities: to design an experiment, to introduce a person to research, to translate science into policy.

This volume of Sleep Health contains original reports and reviews written by trainees and colleagues of Dr. Czeisler. This Festschrift was inspired by a two-day event in honor of Dr. Czeisler in October 2019 at the Biological Laboratories at Harvard University. Over 50 people attended, presented scientific results, and told stories about their times with Dr. Czeisler and the influence he has had on their careers. Our happy memories of this event are deepened by the knowledge that, for many, this was the last large scientific gathering before the COVID-19 pandemic.

Biography

Dr. Czeisler obtained his undergraduate degree from Harvard University magna cum laude, partially based on his thesis, entitled Psychoendocrine study on the effects of anxiety: the nychthemeral pattern of plasma cortisol levels in patients awaiting elective cardiac surgery (A.B. thesis, summa cum laude). He then obtained PhD and MD degrees from Stanford University. His PhD thesis, Internal organization of temperature, sleep-wake, and neuroendocrine rhythms monitored in an environment free of time cues, included a thorough study of sleep, temperature, hormone, and other rhythms in humans using the observed spontaneous desynchrony of the circadian and behavioral rhythms in those participants. Some may recall reading an article in the New York Times about this pioneering work. His first post-doctoral work was as a Senior Fellow in Health Policy at the Harvard JFK School of Government. He has been faculty at Harvard Medical School (HMS) and Brigham and Women’s Hospital (BWH) since 1983, and in 2004 he became the Frank Baldino Jr PhD Professor of Sleep Medicine. He is Chief of the Division of Sleep and Circadian Disorders within Medicine and Neurology at the BWH and Director of the Division of Sleep Medicine at HMS.

Dr. Czeisler has held a number of influential leadership positions in government and professional organizations. He served as National Space Biomedical Research Institute (NSBRI) Leader of the Human Performance Factors, Sleep, and Chronobiology Team; Chair of the National Heart, Lung, and Blood Institute (NHLBI) National Center on Sleep Disorders Research (NCSDR), which leads NIH research efforts on sleep and sleep disorders; and President of the Sleep Research Society. He has received multiple honors and awards, including national top 40 of the Westinghouse Science Talent Search; The William C. Dement Academic Achievement Award from the American Academy of Sleep Medicine; The Director’s Award for Scientific Leadership in Occupational Safety and Health from the National Institute of Occupational Safety and Health; honorary fellow of the Royal College of Physicians (London); member of the American Clinical and Climatological Association; Lifetime Achievement Award from the National Sleep Foundation; Lord Adrian Gold Medal of the Royal Society of Medicine (London); Distinguished Scientist Award from the Sleep Research Society; Mark O. Hatfield Public Policy Award from the American Academy of Sleep Medicine; member of the Institute of Medicine of the National Academies; full member, International Academy of Astronautics; Mary A Carskadon Outstanding Educator Award from the Sleep Research Society; Johnson Space Center Director’s Innovation Award (to the International Space Station Flexible Lighting Team) from the NASA Johnson Space Center; Inaugural Fellow of the American Physiological Society; the Green Cross for Safety Innovation Award (for Brigham Health Sleep Matters Initiative) from the National Safety Council; and the J.E. Wallace Sterling Lifetime Achievement Award in Medicine from the Stanford University School of Medicine Alumni Association.

Dr. Czeisler’s trainees are now based at universities and medical schools on 6 continents, many of whom lead influential programs. Dr. Czeisler’s legacy is evidenced by the far-reaching and impactful contributions he and his former trainees continue to make to the field. Dr. Czeisler has authored over 300 peer-reviewed publications – and (as his trainees know) he sees writing and editing each publication as an opportunity to teach the scientific method and writing (and tell stories!). He has co-authored reports for the US Institute of Medicine, US National Academy of Sciences, US Congress Office of Technology Assessment, and US Department of Transportation, and he has been featured in television documentaries.

Most importantly, Dr. Czeisler’s research has been inspired by his passion to improve lives and change policy. This special issue of Sleep Health provides a sample of the depth and breadth of Dr. Czeisler’s research impact. This impact spans the fields of sleep and circadian medicine: basic science (e.g., effects of light on the human circadian system), translational clinical work, advisory work (e.g., melatonin and its agonists and modafinil), and public policy (e.g., drowsy driving, work hours and safety, daylight saving time). We have divided this special issue into four sections (summarized below), reflecting the far-reaching contributions and impacts of Dr. Czeisler’s research and that of his trainees. We end this introductory perspective with Dr. Czeisler’s description of the importance of mentors in his life.

Section 1. Fundamental properties of the human circadian pacemaker and sleep (by KP Wright)

The circadian time keeping system regulates human biology and behavior across the 24-hour day so that humans are prepared for—not simply reactive to—changes in the environment. Dr. Czeisler has explored fundamental properties of the circadian time keeping system in humans throughout his career, including, but not limited to, the regulation of sleep by the circadian pacemaker in the suprachiasmatic nucleus (SCN) (Czeisler et al., 1985; Dijk et al., 1994, 1995), the influence of circadian rhythmicity on physiology and behavior (Johnson et al., 1992; Boivin et al., 1997; Duffy et al., 1999; Czeisler et al., 1999; Wright et al., 2002; Buxton et al., 2012; Burke et al., 2015), the impact of light exposure on human circadian rhythms (Czeisler et al., 1986, 1989, 1995; Jewett et al., 1991; Boivin et al., 1996; Zeitzer et al., 2000; Khalsa et al., 2003; Gronfier et al., 2004; Gooley et al., 2010; Chang et al., 2011, 2012, 2015; Kent et al., 2022; St Hilaire et al., 2022), mathematical models of the circadian pacemaker and its resetting by light (Kronauer et al., 1982; Klerman et al., 1996; Brown & Czeisler, 1992; Brown et al., 1997; St Hilaire et al., 2007), the intrinsic period of the human circadian clock (Czeisler et al., 1999; Scheer et al., 2007; Duffy et al., 2011; Wang et al., 2023), circadian entrainment (Czeisler et al., 1981; Klerman et al., 1998; Wright et al., 2001; Gronfier et al., 2007), and application of knowledge of circadian rhythms and sleep physiology for the treatment of shift work and circadian rhythm disorders (Czeisler et al., 1981, 1982, 1990, 2005; Landrigan et al., 2004, 2020; Rajaratnam et al., 2015).

Dim light melatonin onset (DLMO) is the most commonly used circadian phase marker in humans, and the phase relationship between DLMO and bedtime is the most commonly used metric of the phase of entrainment. In this issue, Cox et al. (2023) examined the timing of dim light melatonin offset (DLMOff) as a circadian phase marker representing the end of the biological night, and its relationship to waketime and chronotype. They showed the range of clock hours of DLMOff in 62 healthy participants was ~7 hours, and that the range of DLMOffs relative to waketime was ~4 hours, with 74% of DLMOffs occurring after waketime. This suggests that many people are awake in the morning during their biological night; this may be a type of misalignment between the circadian system and chosen waketime behaviors.

Circadian rhythms have been reported in the human transcriptome (Archer et al., 2014), human proteome (Depner et al., 2018), and human metabolome (Dallman et al., 2012; Chua et al., 2013; Skene et al., 2018) supporting the widespread influence of circadian rhythms on cellular processes. “Omics” technologies applied in the context of circadian rhythms hold promise to advance our understanding of human physiology and disease broadly, to explore processes that are dysregulated when circadian rhythms are disturbed, and to be used as circadian biomarkers. In this issue, Specht et al. [PLEASE CITE SLEH_916]. used the constant routine (CR; Duffy & Dijk, 2002) circadian protocol to examine the human proteome and they report that hundreds of the ~7,000 proteins examined show circadian rhythms. The findings improve our understanding of human circadian rhythms in multiple tissue and cellular biological processes as measured by the circulating proteome.

Cognitive function is worse during the biological night, especially for individuals in occupations with extended work hours. In this issue, Boivin et al. (2023) used an ecological momentary assessment approach to collect data on subjective alertness and objective performance data from 76 police officers during real-life day and night shifts. They found that changes in subjective alertness with increasing time awake were positively correlated with changes in performance response speed when all data were pooled. When individuals’ data were examined, only ~64% of participants had this positive correlation; the remaining participants had a mismatch in direction of change between their subjective and objective measures.

Mathematical models have been developed to predict performance deficits and perform in silico testing of countermeasure strategies to improve alertness and performance during the biological night. In this issue, Phillips, St. Hilaire et al. (2023), used a biomathematical model to predict the performance of 169 medical residents who participated in a multicenter, cluster-randomized, crossover trial that eliminated extended work shifts. Their model linked three key components for real-world performance prediction: (1) a dynamic model of the human circadian pacemaker and its response to light/dark and sleep/wake timing; (2) a model of effects of chronic sleep restriction on performance; and (3) inclusion of actual real-life sleep/wake and light/dark timing inputs. The model results suggest two target areas for future improvement of resident work schedules: The first is recognition of performance vulnerability during work hours from 0800 to 1100h and the second being a moderately impaired state following short between-shift intervals (i.e., quick returns < 10 hours in duration).

Menstrual cycle phase is a physiological factor reported to influence cognitive function during the biological nighttime. For example, lower core body temperature and worse performance have been reported in women during the follicular compared to luteal phase of the menstrual cycle (Grant et al., 2020; Wright & Badia, 1999). In this issue, Grant et al. (2023) conducted an analysis of the acute effects of monochromatic light exposure of varying spectra and intensities as a countermeasure for menstrual phase-dependent cognitive impairments at night. They found that participants who showed melatonin suppression greater than 33% in response to the light exposures also showed higher body temperature and better performance, without any changes or differences in subjective sleepiness.

Chang, Anderson, et al. (2023) examined circadian entrainment to gradual versus immediate 8-hour phase advances of the light-dark cycle with and without exposure to short-wavelength green light, white light, or green-enriched white light. They found that the combination of an immediate shift of the light-dark cycle, which also included naps, with a gradual advance in the timing of green-enriched white light during the light-dark cycle produced the largest phase shift across the 5 days. None of the interventions, however, were sufficient to fully entrain participants’ circadian rhythms to the 8-hour phase advance. In addition to their importance for shiftwork and jetlag adaptation and managing circadian disruption, “these findings with green-enriched polychromatic light challenge the oversimplification that blue light is always more effective than green light in inducing circadian resetting responses in humans.”

Ultradian rhythms are also present in human physiology; the non-rapid eye movement (NREM)-rapid eye movement (REM) sleep cycle is a well-known example. Cajochen et al. (2023) examined the distribution for the duration of NREM-REM sleep cycle across the night using 6064 archived polysomnography recordings from 369 participants. They found the median NREM-REM sleep cycle duration to be 96 minutes and that across the sleep opportunity, distributions for the duration of NREM sleep (within the NREM-REM sleep cycle) narrowed and for REM sleep (within the NREM-REM sleep cycle) widened. They further found that being female, older age, and having experienced prior sleep deprivation were associated with longer NREM sleep durations within the NREM-REM sleep cycle.

Section 2: Circadian sleep-wake interactions (by JF Duffy)

Under usual entrained conditions, the rhythm in sleep-wake propensity driven by the circadian system interacts with a sleep-wake homeostatic process to allow humans to have a long bout of wakefulness each day and a long and consolidated bout of sleep each night (Dijk & Czeisler, 1994, 1995). Dr. Czeisler’s refinement of the forced desynchrony protocol (FD; Czeisler et al., 1999; Wang et al., 2023), first used by Kleitman in studies in Mammoth Cave in the 1930’s (Kleitman, 1939), has been a remarkable tool to understand how these two sleep-wake regulatory processes interact in humans, informing our understanding not only of sleep (Dijk et al., 1999), but of waking neurobehavioral performance (Dijk et al., 1992; Wyatt et al., 1999; Lee et al., 2009), mood (Boivin et al., 1997; Koorengevel et al., 2003), cardiovascular function (Scheer et al., 2009; Scheer et al., 2010), metabolism (Zitting et al., 2018), and other aspects of human physiology. In this section, authors describe new findings related to understanding circadian and sleep-wake interactions, and the performance and health consequences when those interactions are altered.

The papers by Aeschbach et al. (2023), Broussard et al. (2023), and Yuan et al. (2023) used the FD protocol to explore circadian and sleep-wake interactions. Yuan and colleagues used a 28-hour FD protocol to examine the ability to remember the name associated with a novel face, a critical skill in both social and occupational situations. As with most other aspects of human neurobehavioral performance that have been tested, face-name recognition deteriorated with increased time awake and showed significant circadian variation, with worst performance in the early biological morning. Both Aeschbach and Broussard used a 42.85-hour FD protocol. In the Aeschbach (2023) study, they also imposed chronic sleep restriction and examined the interactions of acute and chronic sleep loss and circadian timing on slow eye movements, a physiological measure of attentional failures. They found that 10-hour sleep episodes could temporarily reverse attentional impairments during the first ~8 hours awake. However, during the subsequent waking hours, attentional failures increased steadily and at a faster rate as the 3-week experiment progressed, and the effects of acute and chronic sleep loss were magnified during the biological night compared to the biological day. Broussard and colleagues (2023) found that both time awake and circadian phase modulated glucose levels, with peaks in glucose after each meal and decreases during the extended sleep/fasting episodes. They also report lower overall glucose levels during the late biological daytime that rose throughout the biological night and then peaked in the biological morning when glucose levels then remained fairly stable over the first half of the biological day. The complex interactions between time awake, circadian phase, and chronic sleep loss revealed in FD studies are especially important in understanding the impact of duty schedules on shiftworkers, and in designing schedules that aim to reduce the risks of insufficient sleep and round-the-clock operations on productivity, health, and safety.

The paper by Scheuermaier et al. (2023) used the CR protocol to explore whether secretion of the hormone aldosterone is under circadian regulation or under sleep-wake control (as had been demonstrated previously). They found a sleep-independent circadian variation of aldosterone, with higher levels at the end of the biological night and lower at the end of the biological day. Aldosterone was also significantly higher during the recovery night following the sleep deprivation inherent in CR conditions, indicating both circadian and sleep-wake regulation of this hormone. These findings contribute to our understanding of how fluid balance and urine output are controlled, and why daytime sleep episodes may be interrupted by the need to urinate.

The papers by Hilditch et al. (2023), Lammers-van der Holst et al. (2023), and Zimberg et al. (2023) relate to the disruption of circadian-sleep-wake interactions that occur as a result of night shift work. Lammers-van der Holst and colleagues (2023) carried out an observational study to evaluate sleep strategies used by shift workers between night shifts and identified four distinct strategies. Their results may help design new sleep interventions that can be individualized to the worker’s preferred sleep timing. In the study by Zimberg and colleagues (2023), they examined how individual differences in circadian adaptation to night work influenced daytime sleep architecture. Participants who were at least partially adapted to the night shift schedule after a week slept longer and had more REM sleep during that week, highlighting the importance of alignment between sleep-wake cycle timing and the circadian phase of sleep. Hilditch and colleagues (2023) tested whether light-emitting glasses, a field-deployable light source worn by participants sleeping in their own homes, would mitigate sleep inertia upon waking at night, as is necessary for many on-call workers. The participants rated themselves as more alert and energetic when the glasses were turned on compared to when they were off and showed better working memory task performance when waking from slow wave sleep. Psychomotor vigilance task performance, however, was worse in the light condition. Thus, this study highlights one of the challenges of translating a laboratory-demonstrated intervention into the field and reinforces the importance of evaluating the feasibility and efficacy of interventions in real-world environments.

Section 3: Circadian and sleep medicine (by FAJL Scheer)

While sleep medicine is well-established, with >2,500 certified US sleep medicine facilities (https://aasm.org/), circadian medicine and its clinics are still in a nascent stage. Public, scientific, and medical recognition of the importance of sleep and circadian health continues to grow, and the first circadian health clinics are being established around the globe (https://circadianhealthclinics.com/), thanks in part to the pioneering research and advocacy work of Dr. Charles Czeisler. This section includes publications with relevance to sleep/circadian health and disease.

Some areas of investigation are sleep extension, sleep-timing variability, circadian phase and cardiometabolic outcomes. Mathew et al. (2023) found that one week of sleep extension (~43 min/night) vs. habitual sleep (before-after analysis; i.e., no control group) in 12 college students decreased systolic blood pressure by ~7 mmHg, post-prandial glucose concentrations, sedentary time, and percentage of wake time spent in moderate-to-vigorous activity. In sub-analysis, those extending sleep by ≥20 min also had improved hydration status (by kidney function metrics). Further studies are justified, particularly those including a randomized design, larger sample size, and investigation of the role of physical activity, eating/drinking behavior, and kidney function. Shafer et al. (2023) investigated 10 night shift and 10 day shift nurses in a cross-sectional study, showing that, compared to day shift nurses, night shift nurses had a later DLMO, more sleep-onset variability, and reduced sleep-episode-associated blood pressure dipping on non-work days. In night workers only, the later circadian phase and sleep variability were each negatively associated with blood-pressure dipping. Future longitudinal and experimental studies are needed to test causality and mechanisms underlying the blunted blood pressure dipping.

Another area of investigation is circadian rhythms in mood, wellbeing, and nausea. Zitting et al., utilizing FD (n=34) and CR (n=81) protocols, demonstrated a consistent endogenous circadian rhythm in nausea peaking at the end of the biological night. Scheer and Chellappa, using a CR protocol, showed an endogenous circadian rhythm in depressive-like and anxiety-like mood and wellbeing in 19 healthy participants, with worst ratings of all measures around habitual waketime. Emens and Lewy, studying 25 first-year medical students, found that a later DLMO relative to mid-sleep was associated with worse mood. These studies add to the larger literature on the link between circadian rhythms and mood, with potential relevance for the prevention, development, and treatment of mood disorders.

A third area is using “-omics” to investigate mechanisms underlying sleep disorders. Cade and Redline (2023, forthcoming) investigated the genetics of the co-occurrence of clinically diagnosed insomnia and sleep apnea (COMISA) in ~50,000 individuals; they found minimal shared genetic architecture between sleep apnea and insomnia, suggesting genetically distinct COMISA components. Future studies with a larger sample size and refined (sub)phenotyping may help understand and treat COMISA. Cederberg et al. (2023) applied proteomics to identify biomarkers of periodic limb movements (PLM) and restless legs syndrome (RLS) in 1400 adults and a replication cohort. Results link PLM with iron deficiency (ferritin, hepcidin) and proteolytic enzyme activity (Cathepsin A), without a clear link for RLS. These results provide further mechanistic evidence underlying PLM and justify follow-up in larger-scale studies.

Section 4: Sleep, circadian rhythms and public health (by A-M Chang)

Sleep is linked to human health on multiple levels. As we learn and understand more about the complex biopsychosocial and behavioral aspects of sleep, we gain insights into the health of individuals and populations. Dr. Czeisler’s work has critically and broadly impacted sleep research and sleep medicine in the public health domain.

Individuals around the world experience myriad factors that influence their sleep health. Although language, culture, customs, and many other contextual variables differ among countries and populations, the goals of research to improve sleep health and to inform public policy focused on optimizing and prioritizing sleep remain the same. Two studies in this section examined the sleep of adolescents living in rural populations. Scheuermaier et al. (2023) evaluated multiple dimensions of sleep in 900 adolescents living in rural and urban areas of Nigeria and reported higher prevalence of poor sleep quality, short sleep duration, daytime sleepiness, and risk of sleep apnea in urban, compared to rural, adolescents. Louzada et al. (2023) examined actigraphy-derived sleep metrics and exposure to late evening electric light (LEEL) in adolescents living in rural areas of Argentina (n=32) and Brazil (n=27). They found an association between LEEL and delayed sleep onset, shortened sleep duration, and lower sleep regularity. These studies provide valuable insights to better understand the role of urban and rural settings in the sleep health of adolescents.

Johnson et al. (2023) also examined the association between actigraphy-derived sleep metrics and light exposure in 6,089 US adults (2011–2014 National Health and Nutrition Examination Survey, NHANES). This study focused on the role of race/ethnicity and sex in this relationship and found that exposure to light at night (LAN) was most common among Black participants, and the association with sleep duration varied by race/ethnicity and sex; exposure to LAN was associated with higher prevalence of short sleep among Black, Mexican, and White women and Mexican and White men. These findings support further examination of the intersection among LAN, race, ethnicity, gender, and sleep.

Several studies assessed sleep health in specialized groups of workers providing service and/or care to the public. First, Tanigawa et al. (2023) reported findings of a sleep intervention, continuous positive airway pressure, in 122 workers of the Fukushima Nuclear Power Plant. They found an association between treatment for those with obstructive sleep apnea (OSA; n=15) and changes in sleepiness and insomnia symptoms in all workers (with and without OSA) sleeping in the same shelter following the deadly 2011 earthquake, tsunami, and nuclear disaster in Japan. Those with OSA reported improvement of their sleepiness, and those without OSA reported improvement of their insomnia symptoms. Next, Weaver et al. (2023) presented results of a 2022 nationally representative cross-sectional survey of 4,763 US adults designed to characterize public opinion regarding resident physician work hours and current regulations and policies. The authors found that the majority of the public disagreed with current work hour regulations and did not support extended duration shifts for resident physicians. Lastly, in another 2022 cross-sectional survey of 6,260 US adults, Czeisler et al. (2023) examined sleep and mental health in unpaid caregivers of children, adults, and both children and adults. They found that unpaid caregivers disproportionately experience adverse effects on sleep health (e.g., insufficient, impaired, or disordered sleep) and mental health symptoms of anxiety, depression, and burnout, compared to those with no caregiving responsibilities. Furthermore, these negative impacts on sleep and mental health were worse for those with dual-caregiving roles. These studies highlight the critical need for public recognition, support, and services (including treatment) to improve sleep health of those who provide vital care and assistance to others.

Concluding Statement: The Importance of Mentorship (by CA Czeisler)

Fifty years ago, on July 17, 1973, I collected my first blood sample for a research study, and continued doing so every 20 minutes for the next 24 hours, in order to assess the nychthemeral pattern of cortisol secretion in a patient the day before open heart surgery (Czeisler, 1974; Czeisler et al., 1976). That first blood sample for my undergraduate thesis project was preceded by about six months of planning. The study design was inspired by Dr. David Hamburg’s elegant study of the parents of children with neoplastic disease, who he had collect their urine in jugs over full 24-hour intervals every day for months. He discovered that the parents of children who suffered a cancer relapse exhibited markedly increased concentrations of a cortisol metabolite in their urine after hearing distressing news about their children’s prognosis (Hamburg, 1962). When I recounted to Dr. Jim Orr, my undergraduate tutor in biochemistry and molecular biology at Harvard College, my amazement that a change in emotional state could elicit a biochemical change in the body, Jim referred me to the then-recent discovery by Dr. Elliott Weitzman of the episodic pattern of cortisol secretion (Weitzman et al., 1971). I then drove to New York to visit Elliott’s lab at Einstein/Montefiore. There, Dr. Howard Roffwarg patiently demonstrated the system involving 12-foot long narrow-lumen tubing that Elliott had developed to sample blood from outside a participant’s room during sleep—a modified version of which we are still using five decades later. Most studies of psychological distress at the time were conducted by collecting a single blood samplebefore and a single blood sample after participants watched a scary movie—with decidedly mixed results. My goal was twofold: 1) collect multiple frequent samples of blood around the clock so that I could account for both the episodic secretory pattern and the circadian variation in cortisol secretion; and 2) use a naturally occurring situation that reliably induced significant anxiety and fear of bodily harm by studying patients awaiting elective coronary artery bypass graft surgery. I was hoping to get a “jump start” on my thesis over the summer while I was home in Chicago. My father, the late Dr. Tibor Czeisler, suggested that I speak with Dr. Toma Hoeksema, a cardiovascular surgeon in Chicago who performed several coronary artery bypass graft procedures every week. He was excited about the proposed project, and he helped me obtain permission to conduct the studies of pre-operative patients at the St. Francis Hospital in Blue Island, Illinois. Dr. Norman Gold, another of my advisors at Boston Children’s Hospital, then arranged for me to work in the laboratory of Dr. Edward Ehrlich at the University of Chicago, where I set up a competitive protein binding assay to measure cortisol concentrations in the 670 plasma samples that I eventually collected. Once I got the assay working, I was able to measure plasma cortisol concentrations in about 25 samples per day. When I returned to Boston, Dr. Gold suggested that I contact Dr. Francis D. Moore, the iconic Chair of Surgery at the Peter Bent Brigham Hospital, who assigned a graduate student to work with me and arranged for me to carry out studies in healthy non-surgical controls in the Thorn Clinical Center there, which was led by Dr. Gordon Williams. Analyzing the data on cortisol secretion that I collected taught me an enormous amount about the secretion of that hormone and about circadian rhythmicity.

I then decided to attend Stanford Medical School to work with Dr. David Hamburg, who had inspired my interest in the field. When I arrived at Stanford, David informed me that Dr. Elliott Weitzman was on sabbatical there, working in the laboratory of the famed sleep researcher Dr. William C. Dement. Elliott convinced me to add polysomnography while carrying out additional studies. When an equipment failure delayed the bedtime of one of the participants in that study by several hours, I was amazed to see that the delayed bedtime had as profound an impact on the cortisol secretory pattern as I had observed in the patients before open heart surgery, albeit in a different direction. At that point, I became fascinated by the relationship between the sleep and circadian regulation of hormonal secretion. Consequently, 48 years ago, on July 17, 1975, working in Dr. Elliott Weitzman’s laboratory in New York, I began the first study of a human participant living in an environment free of time cues, which formed the basis of my doctoral thesis in the Neuro- and Biobehavioral Sciences at Stanford University (Czeisler, 1978; Czeisler et al., 1980, 1980, 1981, 1981). When I reviewed my findings with Dr. David Hamburg, who by then was President of the Institute of Medicine at the National Academies (now the National Academy of Medicine), David convinced me to forego my planned residency in neurology after my upcoming graduation from Stanford Medical School and instead join him as a Senior Fellow in Health Policy at the Division of Health Policy he was establishing at Harvard’s John F. Kennedy School of Government so that I might carve out a new area of occupational medicine related to the scheduling of work in round-the-clock operations—thereby fostering my enduring interest in what today would be called translational research (Czeisler et al., 1982).

I recount this history of how my career started to convey how deeply my career was supported by the many mentors who generously shared their wisdom, time, and expertise with me, and who provided me opportunities at every step of the journey. That experience has motivated me throughout my own career to support the many undergraduate students, graduate students, and post-doctoral fellows who have expressed to me an interest in research. That is why this Festschrift, or “Celebration Writing,” by many of the trainees and colleagues who have worked with me over my career means so much to me, and I want to take this opportunity to thank each author for your contribution both to this volume and to the scientific research that we have done together over the years. I am very, very grateful to Shantha M. Wilson Rajaratnam and Elizabeth B. Klerman, who organized the in-person Festschrift conference in the Biological Laboratories at Harvard University in October, 2019 and who have edited this volume, and to the Section Editors, Anne-Marie Chang, Jeanne F. Duffy, Frank A.J.L. Scheer, and Kenneth P. Wright, Jr., for all of their hard work in reviewing and editing this Festschrift. Finally, I want to thank Orfeu M. Buxton, Editor-in-Chief of Sleep Health; Amanda Applegate, Senior Journal Assistant at Sleep Health; Meir Kryger, Art Editor at Sleep Health; Inne Barber and Joseph M. Dzierzewski, Vice Presidents of the National Sleep Foundation; John Lopos, CEO of the National Sleep Foundation; and the Board of Trustees of the National Sleep Foundation for their support and encouragement of this Festschrift.

Funding:

EBK: NIH R01-NS099055, U01-NS114001, U54-AG062322, R21-DA052861, R01-NS114526-02S1, R01-HD107064; DoD W81XWH201076; and Leducq Foundation for Cardiovascular Research Leducq Trans-Atlantic Network of Excellence On Circadian Effects in Stroke

SWR: Monash University; Australian Research Council; National Health and Medical Research Council

KPW: NIH R01-HL165343, R01-HL159647.

JFD: NIH R01-HL148704, R01-AG044416, R01-DK127254, R21-HL161464.

FAS: NIH R01-HL140574, R01-HL153969, R01-HL164454, R01-HL167746, R01-DK124280, R01-DK127254, U01-DA059472; and Leducq Foundation for Cardiovascular Research Leducq Trans-Atlantic Network of Excellence On Circadian Effects in Stroke

AMC: NIH R01-HD073352, R01-NS113889, Kunasan SRA #231161

CAC: Frank Baldino, Jr., Ph.D. Professorship of Sleep Medicine

Overall: Support for 2019 in person meeting: Gifts from Vanda Pharmaceuticals, Phillips Respironics, Johnson & Johnson Services, Inc.

Declaration of Conflicts of Interest

EBK: Consulting: American Academy of Sleep Medicine Foundation, Circadian Therapeutics, National Sleep Foundation, Sleep Research Society Foundation, Yale University Press. Travel support: European Biological Rhythms Society, Sleep Research Society, EPFL Pavilions, World Sleep Society. Other: unpaid scientific board member of Chronsulting; partner is founder, director, and chief scientific officer of Chronsulting.

SWR: Consulting (through my institution): Circadian Therapeutics, Vanda Pharmaceuticals, Roche, Avecho. Research funding: Whoop Inc; Sponsored webinar: Phillips. Chair, Sleep Health Foundation.

KPW: Scientific advisory board: the U.S. Army Medical Research and Materiel Command-Walter Reed Army Institute of Research, outside the submitted work. Research support/donated materials: DuPont Nutrition & Biosciences, Grain Processing Corporation, and Friesland Campina Innovation Centre, outside the submitted work.

JFD: no conflicts to report.

FAJLS: Board of Directors: Sleep Research Society. Consulting: the University of Alabama at Birmingham and Morehouse School of Medicine, outside the submitted work. Interests were reviewed and managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies.

AMC: Grant support to the Pennsylvania State University from Kunasan, Inc., outside the submitted work. Honoraria from the University of Miami.

CAC: CAC serves as the incumbent of an endowed professorship provided to Harvard Medical School by Cephalon, Inc. and reports institutional support for a Quality Improvement Initiative from Delta Airlines and Puget Sound Pilots; education support to Harvard Medical School Division of Sleep Medicine and support to Brigham and Women’s Hospital from: Jazz Pharmaceuticals PLC, Inc, Philips Respironics, Inc., Optum, and ResMed, Inc.; research support to Brigham and Women’s Hospital from Axsome Therapeutics, Inc., Dayzz Ltd., Peter Brown and Margaret Hamburg, Regeneron Pharmaceuticals, Sanofi SA, Casey Feldman Foundation, Summus, Inc., Takeda Pharmaceutical Co., LTD, Abbaszadeh Foundation, CDC Foundation; educational funding to the Sleep and Health Education Program of the Harvard Medical School Division of Sleep Medicine from ResMed, Inc., Teva Pharmaceuticals Industries, Ltd., and Vanda Pharmaceuticals; personal royalty payments on sales of the Actiwatch-2 and Actiwatch-Spectrum devices from Philips Respironics, Inc; personal consulting fees from Axsome Therapeutics, Bryte Foundation, With Deep, Inc. and Vanda Pharmaceuticals; honoraria from the Associated Professional Sleep Societies, LLC for the Thomas Roth Lecture of Excellence at SLEEP 2022, from the Massachusetts Medical Society for a New England Journal of Medicine Perspective article, from the National Council for Mental Wellbeing, from the National Sleep Foundation for serving as chair of the Sleep Timing and Variability Consensus Panel, for lecture fees from Teva Pharma Australia PTY Ltd. and Emory University, and for serving as an advisory board member for the Institute of Digital Media and Child Development, the Klarman Family Foundation, and the UK Biotechnology and Biological Sciences Research Council. CAC has received personal fees for serving as an expert witness on a number of civil matters, criminal matters, and arbitration cases, including those involving the following commercial and government entities: Amtrak; Bombardier, Inc.; C&J Energy Services; Dallas Police Association; Delta Airlines/Comair; Enterprise Rent-A-Car; FedEx; Greyhound Lines, Inc./Motor Coach Industries/FirstGroup America; PAR Electrical Contractors, Inc.; Puget Sound Pilots; the San Francisco Sheriff’s Department; Schlumberger Technology Corp.; Union Pacific Railroad; United Parcel Service; and Vanda Pharmaceuticals. CAC has received travel support from the Stanley Ho Medical Development Foundation for travel to Macao and Hong Kong; equity interest in Vanda Pharmaceuticals, With Deep, Inc, and Signos, Inc.; and institutional educational gifts to Brigham and Women’s Hospital from Johnson & Johnson, Mary Ann and Stanley Snider via Combined Jewish Philanthropies, Alexandra Drane, DR Capital, Harmony Biosciences, LLC, San Francisco Bar Pilots, Whoop, Inc., Harmony Biosciences LLC, Eisai Co., LTD, Idorsia Pharmaceuticals LTD, Sleep Number Corp., Apnimed, Inc., Avadel Pharmaceuticals, Bryte Foundation, f.lux Software, LLC, Stuart F. and Diana L. Quan Charitable Fund. Dr. Czeisler’s interests were reviewed and are managed by the Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies.

Footnotes

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