Biologist Joseph S. Takahashi, known for his research on circadian rhythms, has had a lifelong love of nature and animals. Growing up in Burma and Pakistan, seeing unique animals such as elephants and camels wasn’t unusual, and fishing trips to the Arabian Sea with his father sparked in Takahashi curiosity about marine biology. Majoring in biology in college would have seemed a natural choice.
However, biology wasn’t Takahashi’s only area of interest. In high school, he completed elective courses such as mechanical drawing, shop and even took three years of auto mechanics. He found taking apart engines and putting them back together fascinating, and for his senior project in auto mechanics, Takahashi and his best friend rebuilt the V8 engine on the latter’s Ford Thunderbird. So it wasn’t biology that Takahashi initially set out to study when he left for Swarthmore College to begin his undergraduate studies—it was bioengineering.
At Swarthmore College in those days, according to Takahashi, being pre-med was the standard for students in the biological sciences. But being a medical doctor didn’t interest him much. As a junior, Takahashi pivoted toward research as a result of interesting lab courses; in particular, he recalls a project on fish that use weak electric fields to navigate at night or in murky waters. “That experiment in particular fascinated me because when I was a kid, I had tons of tropical fish. I loved breeding them, and I’d never seen these electric fish before,” Takahashi says. So he asked for more information about the fish, and they ultimately decided to record the electric discharges over longer periods of time.
They found that the nocturnal fish only discharged electricity during the night, when they were active—during the day, they were electrically silent, an example of a circadian process. As it turned out, the professor teaching the lab course, Kenneth Rawson, studied circadian rhythms in mice, and he allowed Takahashi to do a senior thesis in his lab. Working in Rawson’s lab not only provided Takahashi with research experience, but also led him to meet Patricia DeCoursey of the University of South Carolina, Columbia, in whose lab he worked for one year after graduating. DeCoursey, who was the external examiner for Takahashi’s senior thesis, also had a lab studying circadian processes, and she provided mentorship that helped him choose where to attend graduate school.
For his PhD in neuroscience, Takahashi chose to continue to work on circadian rhythms under Michael Menaker of the University of Texas, Austin (the group later moved to the University of Oregon, Eugene). As a graduate student, Takahashi used the pineal glands of birds to study circadian biology and demonstrated that there were key similarities between how circadian processes are regulated in mammals and birds. Then, as a postdoctoral researcher under Martin Zatz of the National Institute of Mental Health, Takahashi continued his work on how the pineal gland in birds regulates circadian rhythms.
All this work set the stage for Takahashi’s career as a professor studying circadian biology, which began at Northwestern University. There, his group made major contributions to the field, including the discovery of the Clock gene and its partner gene Bmal1 in mice, which act as master regulators of circadian processes. Takahashi’s lab has deeply investigated the molecular pathways in which Clock is involved and found links between circadian rhythms and several important processes. They now even have a project searching for a connection between the Clock gene and lifespan in mice, and they have found enough clues to provide fodder for more research for years to come.
Although his training in circadian-rhythm research dating back to his undergraduate days has undoubtedly been essential to his success in the field, Takahashi recalls his days working in the garage as a high schooler as being some of the most important in shaping his scientific career. It’s not only that this work gave him an understanding of how machines work—although this is a valuable skill, as Takahashi’s group has demonstrated by building custom apparatuses for their hundreds of mice that would have cost millions of dollars had the lab purchased them prefabricated.
But perhaps more importantly, the auto mechanics courses gave Takahashi practical experience in how things work and an appreciation for the importance of understanding that. This is something he tries to impress on budding scientists, especially in an era when much of molecular biology research is done using premade kits—often with proprietary ingredients—and when so much work with big data is done using scripts put together by others. Takahashi is adamant that researchers should have a full understanding of each experiment they do, taking care to learn why protocols are done in specific ways and what kinds of artifacts can be found in the results. “You always have to start with first principles,” Takahashi says.
Takahashi has received numerous awards and honors, including membership in the American Academy of Arts and Sciences, National Academy of Science, National Academy of Medicine and selection as an Investigator by the Howard Hughes Medical Institute.