Circadian Rhythm Science Lesson

Credit: Howard Hughes Medical InstituteThe above graphs show data from teenagers and adults who participated in an 11-day activity study. Each person's Horne-Ostberg score was plotted on the x-axis and his average waking time on the y-axis. The Horne-Ostberg survey identifies a person as an "evening" or "morning" type. As part of its annual educational outreach lecture series, the Howard Hughes Medical Institute recently had high school students participate in a large-scale circadian rhythm science lesson. The twist: Some of the students were themselves the subjects of a circadian rhythm experiment. For the past eight years, the HHMI Precollege Science Education Program has reached out to high schools via December talks, called the "Holiday Lectures." The talks are modeled after similar events at other academic institutions, the original being the Faraday Lectures in London, which feature eminent scientists talking to a lay audience about science. December's two-day HHMI lectures, which focused on the increasingly popular research field of circadian rhythms, featured HHMI investigators Joseph Takahashi, a professor of neurobiology and physiology at Northwestern University who studies rhythms in mammals, and Michael Rosbash, a professor of biology at Brandeis University who studies rhythms in fruit flies. Circadian rhythms are the 24-hour light-regulated sleep/wake cycles that govern physiological and metabolic processes.1 Past topics have ranged from infectious diseases to neurobiology to immunology. To pique participating students' interest this past year, and to help them better grasp the somewhat intangible concept of circadian rhythms, Takahashi and Dennis Liu, the HHMI senior program officer in charge of the Holiday Lectures, decided to equip some of the students with a way to monitor their own internal biological rhythms. Thirty-six of the hundreds of students involved in the lectures wore a small actimeter on their wrist--a thin black box resembling a wristwatch minus the clock face--for 11 days, taking it off only before bathing, swimming, or any activity involving immersion in water. The device, conceived of several years ago by Takahashi in conjunction with the U.K.-based company Cambridge Neurotechnology, measures very slight movement. Several varieties of the miniature actimeter (including one that measures light as well as movement) are now sold by Cambridge Neurotechnology for as much as $1,000 each. Editor's Note: In the interest of full disclosure: The organizers of the ActiWatch circadian rhythm study at the Howard Hughes Medical Institute invited The Scientist Senior Associate Editor Eugene Russo to participate in the study along with 36 high school students and 40 HHMI employees. Like all of the participants, he wore a small, movement-sensing actimeter--a black-box-on-a-strap device resembling a wristwatch without a clock face--for 11 days, removing it only to avoid its getting wet. He also filled out a Horne-Ostberg survey, which asks questions about sleeping and waking habits. According to the survey and the actogram, as suspected, he is neither a "morning person" nor an "evening person," but rather somewhere mid-way between the two. Called an ActiWatch, the device is commonly used by researchers to study activity patterns in humans and by some sleep physicians and to diagnose sleep disorders. The watch's movement detector converts movement into an electrical signal. A circuit records electrical signal activity over a particular time resolution (in this case every two minutes); a memory chip records the count. The data is then downloaded into a computer and the participant's "actogram" charted. Data on whether participants were more the "evening type" or the "morning type" was also gathered using the Horne-Ostberg survey--which asks questions such as, "If you went to bed at 11:00 p.m., at what level of tiredness would you be?" and "How alert do you feel during the first half-hour after having woken in the mornings?" A plot of the Horne-Ostberg score versus the average waking time indicated by the actogram suggests a measure of how well a person's actual schedule fits preferred activity patterns. A lecture by Takahashi revealed some interesting, though not necessarily surprising, details about the activity data provided by the 36 participating students. "I think students got a sense of how messy it is to interpret this kind of information," comments Liu. "At the same time we had some real conclusions." When compared with the activity patterns of 40 Howard Hughes employees, who also wore the watches for 11 days at a time, they came to one major conclusion: teenagers wake up later and sleep more on weekends than do adults. In fact, says Takahashi, many of the students were getting appallingly little sleep--as little as five hours. Rosbash and Takahashi discussed the genetics of circadian rhythms in mammals and fruit flies and illustrated with computer animation the intricate choreography of known circadian rhythm proteins as they interact during sleep/wake cycles. Credit: Courtesy David Osgood, Mini Mitter Co.The ActiWatch wrist-worn activity monitor Reaching a Virtual Audience As with each year's lectures, the general idea was to educate the students about the given topic and about the daily routine of the scientist. "I work very hard to get these lecturers to understand that they're addressing a high school audience," says Liu. "It varies a lot from scientist to scientist as to how successful you can be at doing that." Liu notes that most scientists find it difficult to make the talks interesting, accessible, and low on jargon without watering down the science. "It's the hardest kind of talk to give," he says. Since 1995, Holiday Lecture speakers have addressed not only an audience of high school students who are local to the HHMI headquarters in Chevy Chase, Md., but simultaneously several other groups of high school students via satellite links. Since 1997, the lectures have been Webcast so that any interested party worldwide may look on and ask questions via email. And last year, HHMI set up remote sites where students could listen, watch, and participate in the lectures in real time. The most recent lectures reached audiences in East Lyme, Conn., Miami, Philadelphia, and even the HHMI office in Moscow--the first simulcast to be done internationally. Organizers provide ample opportunity for participants to ask questions from both home and remote satellite sites. At the latest remote sites, students, standing in front of a camera, asked their questions and then heard their responses from the lecturers. All told, HHMI received 500 questions in person, via satellite, e-mail, and phone. Many of the questions got to the heart of the chronobiology field. One student, for example, asked what would happen if the body's clock were not regulated. (Answer: The clock would "free-run" with no regular rhythm; in fact, a small number of blind persons actually have unsynchronized, "free-running" clocks.) Another student asked if people can compensate for lack of sleep. (Answer: Yes. As suggested in the weekend results of the ActiWatch study, the brain does rebound and compensate for lack of sleep to some degree.) "I think it's important for all of us to be aware and more informed about biology and science in general," says Takahashi, noting that the lectures are not just geared toward budding young scientists. "It would be nice if we [scientists] could reach out much more broadly both at high schools and at the university level to nonmajors." Engaging Students Online and In Person Liu says that the ActiWatch study was the most successful lecture-related activity thus far, but other activities have been incorporated into past lectures or set up on the Web, as a byproduct of those lectures. Several "virtual labs," for example, have been created and continue to be available on the HHMI Holiday Lecture Web site. A bacterial ID lab has proven particularly popular with students and educators around the world. Students can do simulated PCR, end up with real gene sequences, and conduct a real BLAST search. "We don't want it to be all conceptual," says Liu. "We want it to be somewhat grounded in what a real lab is like." When lectures on hearts and hypertension were given in 1998, organizers set up an automated blood pressure device and had more than 100 students measure their blood pressure on the first day's lecture. On the second day, one presenter displayed the data and compared teenage to adult blood pressure. For last year's lectures on microbes, Liu considered doing a culture of every lecture attendee upon arrival, then presenting a sample of the results on the second day and drawing some conclusions. He decided against it, however, fearing that someone might test positive for something untoward. Of course, as with any experiment, issues of privacy and consent must be considered. Takahashi recalls the reaction of several of his graduate students to wearing the ActiWatch when he first brought it to his lab for testing a few years ago. While Takahashi himself enthusiastically wore the device for an entire year, many of his graduate students elected to call it quits after only a five-day trial period that happened to coincide with homecoming weekend. "The record actually reveals a lot about what you're doing. It shows when you're not moving and when you're moving," Takahashi remarks. "It became really obvious to them--'I don't know if I want my boss to know what I'm doing every Saturday night.'" For the 2000 lectures, despite the seeming innocuousness of the ActiWatch study, all student participants were required to sign an assent form and their parents a consent form; the Northwestern University Institutional Review Board oversaw the experiment. "That was arguably overkill," says Liu. Lecture topics are typically decided based on what seem to be the hot areas of biomedical research, and which HHMI investigators are considered skilled speakers. Topics are also chosen based on survey feedback from teachers and students. One subject that keeps coming up, says Liu, is cancer; he hopes to organize lectures focusing on cancer and bioinformatics for 2002. Finding an appropriate student activity for the 2001 lectures should be a challenge: the planned topic is "sex determination." "I'm starting to think of something already," he says, adding that, as with the ActiWatch experiment, he's looking to avoid pen-and-paper exercises in favor of a real experiment with real data. S Eugene Russo can be contacted at erusso@the-scientist.com For More Information on the HHMI Holiday Lectures and associated activities: www.holidaylectures.org/

Circadian Rhythm Science Lesson

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