Modern Life and Its Diseases: The Light Connection

Here is something most people don’t know about artificial light: Imagine you’re a researcher with a colony of elderly mice, and you decide that it’s time, after a lifetime of service to science, to put them to rest in the most humane way you can conjure. One surefire method would be to ensure that the lights in their room switch on and off each week precisely six hours later than the preceding week.

If, for example, they are accustomed to the lights coming on at 8:00 a.m. each day, and switching off at 8:00 p.m., change that to 2:00 p.m. and 2:00 a.m. for a week. And then to 8:00 p.m. and 8:00 a.m. the week after. Keep up the rotation and you’ll find that after just a couple of months of such treatment — which simulates chronic jet lag in humans — most of your mice will be dead.

We have no clear idea why this happens — why lab animals quickly expire if exposed to aberrant light cycles; or why plants wilt and flies age faster under artificial days lasting anything other than 24 hours; or why our best and brightest epidemiologists are discovering that more and more human diseases have links to “unnatural” day/night schedules.

We can see the links, but not the underlying mechanism. We just know that they are there — and on an intuitive level, it’s not all that surprising.

Life on this planet is 3.8 billion years old. Over this period, countless species arose. They lived and died in primordial oceans that were acid bodies of freshwater, or on lava-flooded continents under a canopy of volcanic gasses. Some of those species flourished when most of the Earth was a steaming tropical jungle, or in geological eras during which snow covered the land and floating ice drifted to the equator.

Yet, for all the dazzling change, one thing remained constant throughout: The Sun kept rising and setting over the biosphere in a cycle of about 24 hours. Natural selection couldn’t fail to take notice, and has sculpted this history into nearly all living beings, from bacteria to humans, who exhibit circadian rhythms in most of their physiology and behavior.

Sleep and activity levels, hormone secretion and metabolism, even complex mental abilities such as mathematical prowess — all of these wax and wane regularly in 24-hour cycles with astonishing precision. At the most fundamental level, evolution has endowed us with molecular clocks dancing to the music of time in every single one of our cells. In mammals, a brain nucleus called the SCN acts as an orchestra conductor of sorts, marshaling all the peripheral clocks to a single tune thanks to “time-giving cues” from the outside world, of which light is the most important.

Clockwork precision implies an inherent complexity, and this in turn an easily upset organization. What did we expect the consequences would be, then, when the soft glow of the Milky Way was no longer the only thing casting shadows on a clear, moonless night? Whether it is shift work in brightly-lit buildings, late evenings spent staring at a screen, or the gleam of streetlamps straying into one’s bedroom, in evolutionary timescales all these are last-minute inventions. These newfangled ways are now known to be associated not just with psychiatric disorders such as depression, but with certain cancers. This has led government agencies to classify shift work as a probable carcinogen in the same class as nitrogen mustards, obesity and diabetes.

These are the very epidemics that have stalked the West since the lightbulb began its triumphal spread after WWII. And the problem is only going to get worse with the new popularity of tablets and e-readers, as the blueish light emitted by these devices is the most biologically disruptive, while our ancestors, perennially huddled at the edge of night by candlelight and campfires, had been spared for precisely the same reason.

The challenge for science now is to unlock the biological mechanisms underlying these effects of artificial light on our bodies and minds.

The mystery has proved remarkably unyielding. Most people recall from their schooldays that the retina has two types of light detectors: Rods and cones, both of which have been known for centuries — the sort of basic fact whose discovery marks a milestone in the history of medicine, like the circulation of the blood or the germ theory of disease. Imagine the surprise, then, when when scientists discovered just a decade or so ago that this account — while not complete bunk — is certainly not the whole story.

The first suspicions were raised in the 1990s, when it became plain that many blind people still had perfect biorhythms synchronized to the rising and setting of the Sun, even if they moved to a new time zone. How was that possible? The enigma was only solved in 2002, when at long last the retina was caught hiding a third type of photoreceptor, known as “intrinsically-photosensitive retinal ganglion cells,” or ipRGCs for short. This newly discovered receptor proved to be the one responsible for sending light information to the brain for all non-visual purposes, including the setting of the biological clock.

More recent still is the discovery that aberrant light exposure might impair mood and memory even directly — beyond its derailment of circadian rhythms. The exact mechanism is not clear, but researchers have speculated that it alters a neurological circuit that nobody suspected even existed until last year. This means that a whole new neural pathway, existing right beside the classic visual tract, had somehow managed to elude the multitudes.

All of this hints at how primitive our knowledge still is with regard to light and our physiological interactions with it. A breakthrough in this field would immensely benefit human health, by yielding radically new insights into the causes of disorders in which light plays a role.

And if the prospect of defeating diabetes and depression and all the other “diseases of modernity” were not enough, an even more tantalizing promise awaits.

After all, the core evolutionary importance of light — the fact that it was just about the only regularly-timed element during life’s infancy on this planet — has been theorized to have driven the very emergence of memory in biological systems. Likewise, mood may have evolved from a primordial mechanism for an organism to adapt to regular changes in the environment.

Uncovering the ancient neural system that processes light for both mood and circadian regulation could be one long-overlooked key to the great classical questions in neuroscience — most notably the neural underpinning of memory and emotional states.

The development of artificial lighting has allowed humanity to conquer the night and live longer, fuller, more productive lives. Indeed, modern lifestyles are predicated on it to such an extent that it is perhaps unrivaled by any other single invention. Only much later have we come to realize that the benefits do not come without a cost.

That’s not meant as a Luddite renunciation. Rather, it strikes me as an exhilarating scientific challenge. Major breakthroughs could boost the quality of human life to new heights — precisely because we bumped on unsuspected ills on the path of progress, and we did not hesitate to keep up our inquiry. If we succeed, we might just find that the rewards, like a spark of Promethean fire, were well worth the endeavor.

Lorenzo Ospri is a neuroscience Ph.D. candidate in the Hattar Lab at Johns Hopkins University.