Are you a morning lark or a night owl? Scientists use that simplified categorization to explain that different people have different internal body clocks, commonly called circadian clocks. Sleep-wake cycles, digestive activities, and many other physiological processes are controlled by these clocks. In recent years, researchers have found that internal body clocks can also affect how patients react to drugs. For example, timing a course of chemotherapy to the internal body time of cancer patients can improve treatment efficacy and reduce side effects.
But physicians have not been able to exploit these findings because determining internal body time is, well, time consuming. It's also cumbersome. The most established and reliable method requires taking blood samples from a patient hourly and tracking levels of the hormone melatonin, which previous research has tied closely to internal body time.
Now a Japanese group has come up with an alternative method of determining internal body time by constructing what it calls a molecular timetable based on levels in blood samples of more than 50 metabolites—hormones and amino acids—that result from biological activity. The researchers established a molecular timetable based on samples from three subjects and validated it using the conventional melatonin measurement. They then used that timetable to determine the internal body times of other subjects by checking the levels of the metabolites in just two blood samples from each subject per day.
Having such a timetable could allow doctors to synchronize drug delivery to internal body time, the team reports online today in the Proceedings of the National Academy of Sciences. "Usually personalized medicine is focusing on genetic differences, but there are also temporal differences [among patients]. That will be the next step in personalized medicine," says systems biologist Hiroki Ueda of the RIKEN Center for Developmental Biology in Kobe, Japan, who heads the research group.
"In principle, the method holds great promise as a way of replacing the cumbersome melatonin assay," says Steven Brown, a molecular biologist at the University of Zurich in Switzerland. "The authors show in a small-scale, well-controlled experiment that they are able to predict internal body time within a precision frame of 3 hours," says Urs Albrecht of the University of Fribourg in Switzerland. Both researchers say further work will be necessary to make the technique more practical and more widely applicable, and Ueda agrees. The experimental subjects were all young men, and different molecular timetables are likely needed for women and for people of different ages. He would also like to improve the precision and make it reliable with just one blood sample per day.