What makes us get sleepy or stay awake is a complex of protein signals, chemical messengers, and biological responses to our environments.
For example, if you’ve ever seen the television ad for Hetlioz, it is FDA-approved to treat a condition called ‘non-24.’ This technical-sounding diagnosis simply means that its sufferers don’t respond to day/night cycles that correspond to a 24-hour cadence. For example, if a person is blind, he or she does not necessarily get light cues from the outside world to signal what level of physiological vigilance is appropriate. It is one of many chronic circadian rhythm sleep disorders (CRSDs).
After many years of theorizing what happens in our bodies to produce day/night cycles of biological patternicity, Jeffrey C. Hall, Michael Rosbash, and Michael W. Young were just awarded the 2017 Nobel Prize in Medicine for determining that clock genes are involved in our bodies’ ability to properly and adequately signal sleepiness and wakefulness. A particular protein is degraded during the day and accumulates at night, allowing the physiological experience of alertness and somnolence. The Nobel Prize award speech included that “Their discoveries explain how plants, animals and humans adapt their biological rhythm so that it is synchronized with the Earth’s revolutions.”
These clocks are universal in life. They are ticking inside plants, fungi, protozoa, and animals. Circadian, or daily, rhythms are “just as fundamental as respiration,” says Charalambos Kyriacou, a molecular geneticist at the University of Leicester in the United Kingdom. “There isn’t any aspect of biology that circadian rhythms aren’t important for. They are totally fundamental in a way that we didn’t anticipate” before the discoveries honored today.
This work is a capstone on centuries of speculation and research. In 1729, French astronomer Jean Jacques d’Ortous de Mairan showed that mimosa leaves, which open at dawn and close at dusk, continued this cycle even when kept in darkness. It wasn’t until the 20th century that the idea of an internal clock—as opposed one that responds to external cues like light—became settled science. The genetic basis for a daily physiological cycle was first discovered in fruit flies in the 1970s.
Clock genes are extremely influential, affecting the activity of most other genes in the body in one way or another. Circadian mechanisms influence metabolism—how our body uses and stores energy—blood pressure, body temperature, inflammation, and brain function. Time of day can influence the effectiveness of drugs and their side effects. And mismatches between the clock and the environment, for instance as a result of jet lag or shift work, have been shown to play a role in mood disorders and even cancer risk.
Previously, I conducted research on the neuroscience of sleep, and within many sleep clinics there are already trials being developed to test drug treatments for their ability to modify these particular genes to manage hypersomnia or hyposomnia. Current sleep therapies typically bring with them fairly significant side effects and adverse events, such as loss of motor function or cognition, daytime sleepiness, parasomnias, and other phenomena.
If we could precisely target appropriate genetic signals, it would be possible to develop “cleaner” therapies that don’t have as many off-target effects, such as hypnotics often do. Misalignments in this system of clock genes is likely involved in diseases and disorders, and regularly impacts how many people function in the form of jet lag, where periodicity of certain chemicals occurs to how we evolved with the planet and sun, and isn’t easily forceable into artificial reset by jumping timezones. It has also been found that this system totally breaks down when there are no light cues for long periods of time. This is also why pulling the covers over your head or installing room-darkening blinds can help with extending sleep duration.
Elon Musk is sending people to Mars… Who will have trouble sleeping
One of the latest pronouncements from Elon Musk is to have humans sent to Mars by 2024. There are many psychological, physiological, and technological hurdles which must be crossed in order to make this happen, but the actual goal is not that difficult to develop strategies for.
One thing that will be difficult to address is the diurnal cycles experienced by most people compared with what the travelers will have to contend with. Astronauts have notoriously difficult and broken sleep due to a lack of signaling from the sun as to when they should be asleep versus awake, as happens on the surface of the Earth. Some efforts to offset this include timed sleep periods, white noise, and onboard full-spectrum lighting to simulate the light flux during ‘daytime.’
Travelers to Mars will take several months to reach their destination, and so will have no reliable solar signal to tell their bodies what they should be doing. There have been engineering proposals for “torpor-induced hibernation” among other options. Separately, Mars has a ‘day’ which lasts about 40 minutes longer than a day on Earth. This means that every 10 days that elapse on Mars will put our travelers out of sync with Earth by about 7 hours. There have been artificial habitat experiments on Earth to study the effects of precession or recession of time on study participants.
It’s interesting how ubiquitous this clock system is in organisms across the planet. Whether it’s due to divergent evolutionary paths or highly-conserved genes, many plants and animals have been found to have this endogenous protein for regulating day/night cycles. It’s also a potential target for future agricultural techniques where harvest size and yield can be altered by affecting the production of these proteins.