Jeffrey C. Hall: ”Rhythm research is hot as a pistol”

Through the 1980s when there were only three labs studying biological clocks in fruit flies genetically and molecularly the way Hall was, his lab was ridiculed at scientific conferences by other researchers in the rhythm field. The irony was that the disparagement may have created a monopoly for the three labs pursuing their approach, allowing them to push ahead unimpeded, he added.

Now there are tons, as Hall put it, of labs studying circadian rhythms and fewer researchers are laughing at him or fellow Nobel winners Dr. Michael Rosbash, PhD, or Dr. Michael Young, PhD, anymore. They were honored for discovering molecular mechanisms controlling the circadian rhythm, according to the Nobel Prize Committee.

“Our goal was to keep doing what we were doing and liked doing and hope something would come of it,” said Hall. “We were not crushed by all kinds of competitors. It was heady times, to look back at what might have seemed like the bad old days, and enjoyable. Working on rhythms was always interesting; it’s an amazing daily cycle of living organisms’ behavior. Rhythms continue in constant conditions, because of the actions of internal biological clocks.”

They were first to identify a clock gene at the DNA level

Prior researchers had determined that three mutations in a particular gene altered the circadian clock of fruit flies. The insects work well for this type of research because their genes can be accessed molecularly with great proficiency, Hall explained. But it was unclear how the unaltered gene, named period, affected circadian rhythms.

Hall and Rosbash, working together at Brandeis University in Waltham, MA, were able to identify the period gene and determine that PER, the protein encoded by period, increased during the night and broke down during the day. They were the first to identify a clock gene at the DNA level in any organism.

Over 24 hours, PER protein levels fluctuate in harmony with the circadian rhythm, according to the Nobel committee. “It was clear in the 1990s that these genes were not just significant for insects, but relevant to every other creature on the planet, according to Hall.” 

Working together

Rosbash and Hall connected when they became aware of what was going on in each other’s labs at Brandeis, according to Hall. “He [Rosbash] said, ‘You are a geneticist that works with fruit flies, neurobiology, I’m a molecular biologist who works on vertebrates, maybe we could work together.’” 

While the two labored at Brandeis, they were in competition with Young who was working on the same research at Rockefeller University in New York City. “We were aware Young was doing molecular work and he was aware of mutations,” Hall noted. In 1984, Hall and Rosbash and Young independently isolated the PER gene. They finally all connected when a student from Young’s lab contacted Hall with some questions and the competitive relationship became more collaborative. “By the 1990s, we were all working together.”

A career in research

Now retired from Brandeis, where he spent his entire full-time career, Hall’s original goal was to be a “plain old geneticist, studying heredity,” but then his desire grew to add more about biology into his studies and he began taking a more genetic approach to biology, which eventually led to his rhythm studies.

Hall was drawn to genetic research involving fruit flies by a geneticist while an undergraduate biology major at Amherst College.  He had entered college planning to go to medical school, but changed his mind midway through. “It [the research] was very motivational; it made me turn on to doing a career in research.” Hall went on to study genetics at the University of Washington, which exposed him to other research opportunities.

Interest in history and movies

While Hall’s career at Brandeis primarily revolved around genetics research, he is an avid reader and deeply interested in history as well, particularly the American Civil War. He sat in on history courses at Brandeis for two years and then was approached by a member of the history department about teaching a course. Hall wound up teaching a course on the American Civil War over 12 years. “I got to interact with a different part of campus and a whole different group of students.”  Then for two years after retiring he taught a genetics course at the University of Maine. 

Also a huge movie fan, Hall estimates that he watches about 30 films a week from all different genres and decades. “I like everything from the 1930s to the current decade; I find many of them utterly engrossing. I can never predict if I will like or dislike a movie based on its category.” 

Although out of the lab himself, Hall anticipates much more research on circadian rhythms, sleep patterns and sleep, topics of huge interest these days. “There are many irons in the fire, some overly hyped,” he said. “Rhythm research is hot as a pistol, because rhythms are fascinating, comprehensible to almost everyone and exist in every type of organism.”