The Crucial Third Eye

Monday, October 15, 2018

The Crucial Third is the second place winner of the Synapse Storytelling Contest's science writing category. Comments from category judge, Chronicle science writer Erin Allday: The Crucial Third a compelling topic that is clearly of interest to any reader. The writer did a great job of simplifying complex science in a way that balanced readability with accuracy, without compromising either. The end of the piece was a great forward look into where this science is headed, which is often something that’s missing in science writing for laypeople.


For something we spend a third of our lives doing, we understand remarkably little about sleep. Medical professionals and scientists know that it is intricately tied with a swath of health issues- normal immune response, obesity, dementia, cardiovascular disease- but are at a loss explaining what exactly is happening to our bodies during this time.

Sleep isn’t just an ‘off’ state to give our brains a chance to rest. The sleep state is just as complex as wakefulness, requiring the correct activation of a complex orchestra of synchronized switches and flows. Powerful, regular waves of electrical energy emanate from deep in the brain outwards throughout the deeper stages of sleep. Theories of their purpose range from helping form associations between existing memories to scrubbing out nonessential ones. Both, and more, could be occurring, and may even be doing so at different times of night. Our knowledge of this intricate pattern is just beginning to break ground.

Sleeping patterns, like most other human traits, are the result of a mixture of multiple genetic and environmental influences. A trait that is manifested through the actions of many genes is known as ‘polygenic’, with numerous factors contributing to its resulting manifestation. A good example of a highly polygenic trait is human height. Dozens to hundreds of genes, along with the environment, interact to create what each person outwardly displays, distributed amongst the population in a bell curve-like pattern known as the normal distribution. Research indicates that many aspects of our sleep habits also seem to follow this pattern.

Researchers can use the broad natural variation in sleep habits to gain a foothold into understanding more about this mysterious state. Many current studies intend to tease out sleep’s and the circadian rhythm’s genetic components and evaluate their impact for this purpose.

Some of the first advances in sleep-related genetics were the discoveries of components influencing biologically preferred sleep timing. Rhythmic ‘dancing’ between certain proteins in the brain helps determine the timing and tuning of someone’s internal clock. As a result, some individuals exhibit their most natural sleep patterns much earlier in the evening or later at night than the average person – the ‘morning larks’ or ‘night owls’ of popular culture. As this trait is highly polygenic, our ‘chronotypes’ fall more or less along a normal distribution, partly determined by the composition of our DNA.

Research on this subject is becoming especially important due to sleep’s essential role in healthy living and good medicine. As we begin to plunge into the era of personalized medicine, consideration of chronotypes like these should inform how and- more importantly- when we treat patients. Such individual genetic differences in sleep have important medical consequences for personalized treatment and optimal recovery. Scientists know that certain treatments, such as surgeries or vaccinations, are more effective or have better recovery outcomes when introduced to the body at certain points of its daily rhythm. Eventually doctors could schedule all interventions at times when each individual’s body is most receptive to the treatment.

Another line of research suggests there is are extremely rare families able to consistently and naturally sleep fewer hours every night than others. This cohort of ‘short sleepers’ is what my lab, under Dr Ying-Hui Fu, is currently investigating. What about these people’s brains or bodies allows them to do this? Restricted or unrestful sleep over extended periods of time can increase the chances of developing most diseases.

Are these people’s more resistant to constant sleep restriction’s negative consequences or are they in effect sleeping more efficiently?

These questions return us to the electrical brain waves introduced earlier. Only through an understanding of how these processes work can we distinguish good, ‘efficient’ sleep from worse sleep.

At the most fundamental level, everything in the body is governed by molecular interactions. It follows that differences in sleep function can to some degree be attributed to genetic differences between individuals. The electrical patterns in the brain are derived from complex actions across millions of synapses, whose dynamics are in turn dictated by molecular composition and localization. Similarly to what has been observed with chronotypes, minute changes in any protein involved in this network may magnify to generate the individual differences we see displayed.

By finding potential causative mutations in ‘short sleepers’, we may able to tease apart which proteins in the brain are responsible for this behavior. This will improve our understanding of the molecular underpinnings to sleep, which may eventually help mitigate sleep disorders and sleep restriction-related disease by identifying new drug targets.

Scientists are still extremely far off from understanding the molecular bases to sleep architecture. However, advances in genetics have opened a window that allows us to glimpse possible paradigm shifts in the way we view sleep. As personalized medicine takes center stage, treatment for the millions who suffer from sleep disorders may become more nuanced, as each case stems from a unique interaction between genetics and the environment. Perhaps one day we will be able to use our knowledge to individually tailor interventions to grant everyone restorative, healthy sleep.

In the meantime, even as today’s society begins to correctly place more emphasis on diet and exercise, respect for sleep— the third essential component of this health trinity— lags. Sleep isn’t taken seriously enough; much of our culture still celebrates those who can work off less sleep than others. Medicine is starting to change its approach to this crucial third of our lives; individuals and corporations should consider it too.