The Time of Our Lives

We all know the feeling: you settle in for a cozy Saturday morning of sleeping in after a long week of work. The blinds are shut, the alarm is off, and nothing is standing between you and the hours of sleep you crave, and then… you wake up. It’s 6 am, the time at which you force yourself to rise every Monday through Friday for a day at the office. The only thing you want to do is sleep in, but apparently, your brain didn’t get the memo. Like clockwork, your groggy eyes open, and against your will, you’re awake. Actually, it’s exactly like clockwork, and that clock, unfortunately, doesn’t have a snooze button.

Humans, along with so many other living organisms, possess biological clocks called circadian rhythms. They are those inner keepers of time that instruct us when to rise, and sleep. These clocks run on approximately 24-hour cycles and are modulated by sunlight, hence the name (circa diem—around a day).

Back in the 1960s, some biologists were convinced this sense of time was engraved into our genes, the wheels and cogs set in motion before we even emerge from the womb. Famed geneticist Seymour Benzer and his graduate student, Ronald Konopka set about opening up the back of the clock up and revealing exactly what mechanics are behind our daily cycle. They embarked on a journey to discover if, and exactly how, genes could control circadian rhythms. I’d like to think Benzer and Konopka real motivation was to fix that aforementioned unwelcome Saturday morning wakeup call. But in reality, they were called by a higher purpose of elucidating how genes could build the potential for animals to produce behaviors, in this case one’s sense of time. They used an organism none other than the humble (and geneticist’s favorite) fruit fly Drosophila melanogaster to crack the case.

Konopka provided the first evidence that genes could control behavior by looking for mutant flies with clocks that were out of time. He fed normal flies a chemical that created mutations in the DNA of their offspring, and then watched which ones had defective circadian rhythms. Konopka looked for these mutants by monitoring the flies’ movements during a 24-hour day. Flies are usually most active in the mornings and evenings, and enjoy an afternoon siesta. This behavioral pattern is controlled by their circadian clock.

Konopka developed an ingenious tool to monitor the movement of flies over several days. Flies were placed into a box which cycled through a day comprised of 12 hours of light, and 12 hours of dark. The flies’ movements were measured with infrared light within the chamber. Using this apparatus, Konopka discovered 3 distinct clock mutants: arrhythmic, short period, and long period. Normal flies have a rhythm of 24-hours, but the short period mutants had a period of about 19 hours, whereas the long period mutants cycled about every 28 hours. Amazingly, all three mutants were altered in the same gene, which Konopka and Benzer called period, or per for short. Years later, scientists would discover that most organisms, including us, control their biological clocks with the exact same gene that flies use.

Mapping the period gene on the X chromosome of D. melanogaster

With Konopka’s discovery of the period gene, a whole new world opened up. Behavior, a quality seemingly apart from mechanisms and genetics, could be mapped and studied from the inside. No longer was genetics confined to the realm of eye color and body pigment. It could now be used to explain how an animal acts and forms decisions. The discovery of the period gene also showed how an individual gene can build the capacity for significant behaviors.

While researchers still have no remedy for that unwanted Saturday wakeup call, Konopka’s discovery of a clock gene provides a flickering ray of hope. More importantly, Benzer and Konopka’s discovery paved the path for a journey that is still ongoing: the quest to discover how genes build neural pathways for innate behaviors, and the clock was just the beginning.