Resetting the Circadian Clock, continued...

   All of the physiological information going to the digital recorder on the subjects' waists is stored and downloaded daily. On selected days of the protocol, subjects also have an intravenous blood line in their arms from which small amounts of blood are taken every 15 minutes for 26 consecutive hours, using a state-of-the-art miniature blood pump system. A fully equipped blood center processes all the blood extracted from the subjects -- which never exceeds a pint, or the amount one can volunteer to donate to the Red Cross. The blood gets spun down in one of the centrifuges, pipetted into tubes and put in a minus-70-degree freezer. The blood will be studied not only for hormone levels, but for use in other collaborative experiments the laboratory has underway with investigators at Harvard and Baylor on changes in humoral and cellular immune function in response to chronic sleep loss.
   There are also infrared cameras in all the rooms hooked up to closed-circuit monitors at the entrance to the lab. Here at the control console, one of Dinges' students oversees the protocol according to a script that maps out each minute of every day, from nap-time to dinner, lights out to waking, just the way it would be on the ship to Mars. As the subjects prepare to go down for their afternoon nap, Dinges points out that "we deliberately do not give the test subjects their own bedrooms. On a spaceship, quarters are tight, astronauts sleeping right next to each other. Their job is to try to go to sleep. If they can't sleep, they still have to lay there in the dark" -- activities which the infrared cameras allow the lab technicians to track.
   "We try not to burden them with too many probes," Dinges whispers. The subjects get an electrode holiday every four or five days. On those days, they don't have to wear electrodes and they can shower. "Everyone looks forward to those days," he adds, with a smile. "Just psychologically, you can't ask people not to shower for 14 days."
   Who can withstand the rigors of a simulated space flight? All sorts of people, it seems -- provided they're willing to put up with some inconvenience. In the last three years, Dinges has studied more than 100 individuals in sleep deprivation. Subjects complete a screening process that, besides determining their overall fitness for study, also tests their commitment. They wear recording devices at home, and submit to urine tests and psychological tests. They're very healthy people between 22 and 42 years of age, with average or above-average IQs. They're also compensated for their time -- about $100 per day, roughly the equivalent of the minimum wage for a 24-hour working day.
   They earn that $100, and not just for sitting there allowing themselves to be probed. Every day they perform several different kinds of computerized neurobehavioral tests and synthetic work tasks -- most developed in Dinges' lab and used in 1998 NASA space shuttle missions involving Neurolab and Senator John Glenn's recent flight. The tests measure frontal-lobe function and a host of other neuropsychological factors. These neurobehavioral assessment batteries are performed every two hours, for 45 minutes to an hour. Dinges' widely used psychomotor vigilance test is a sustained attention task that measure people's tendency to lapse or drift off. Other tests measure working memory, cognitive speed, ability to estimate time, mood states, mental manipulation and alertness levels. For an electroencephalograph (EEG) assessment, which measures the electrical activity of the brain, subjects stare at a dot for five minutes and aren't allowed to touch their heads. While each subject wears about $15,000 worth of miniaturized technology in the lab, they are also expected to wear a wristwatch-sized recorder for two weeks before and one week after their "voyage" on Starship Dinges.

   It's tempting to imagine that Dinges' research on sleep is motivated by some personal need ("I can't sleep; therefore I will study it"). But no. "I was always regarded as a good sleeper in my family -- going all the way back to infancy," Dinges reports. According to a family story, when he was about nine, his father cut his hair while he slept. "I awoke long after the haircut, none the wiser until my sister's giggling prompted me to look in a mirror -- in those days crew cuts were standard issue for kids in Kansas," he adds. In fact, up through college, "my interest in sleep was mostly as an art form -- something to be enjoyed."
   Not that he had much chance. Dinges received his undergraduate degree from Benedictine College, a modest-sized liberal-arts college on the cliffs overlooking the Missouri River in Atchison, Kansas, about 350 miles east of his home in western Kansas -- which "seemed quite far at the time." Academics were strongly emphasized by the Benedictine monks and "civilian" Ph.D.s who made up the faculty, and it was during those years, Dinges says, that he developed "an intense fascination with psychology, biology, philosophy and mathematics" -- majoring in the first, and minoring in the other three (a course load of 20-24 credits a semester).
   From the age of about 10, Dinges remembers wanting to grow up to be a scientist. "For some reason, I always had a sense that this is what I would do," he says. "It must have come from books or television or great teachers, because where I grew up there were no scientists that I knew. However, my parents stressed the importance and value of education, and the Catholic schools I attended rewarded academic rigor."
   Graduate study in experimental psychology at Saint Louis University -- another 350 miles to the east -- led to Dinges' "obsession with sleep." He studied with Professor Donald Tepas, "a first-rate physiological psychologist," in whose laboratory he undertook his first research involving sleep and the brain, and also worked four summers as the research assistant to Dr. Hallowell Davis at Central Institute for the Deaf and Washington University School of Medicine. "The late Hallowell Davis was among the most inspiring and decent human beings I have had the privilege of knowing and working with. He was internationally renowned for many discoveries and was among a small group of investigators who first recorded the human EEG from scalp electrodes in the 1930s, reporting the first evidence of systematic EEG changes when people went to sleep," Dinges recalls. "The sleep research I performed with Hal Davis while in graduate school served to cement my interest in the topic. Both Professor Davis and Professor Tepas set me on the course I pursue to this day."
   Dinges' first post-graduate position was at George Washington University in Washington (completing his phased move to the East Coast), where he set up and operated an EEG laboratory to study infants born to mothers being treated with methadone, under a federally funded grant to determine if methadone was more harmful to infant brain development than street drugs. During this study, Dinges discovered that "the sleep EEG was a far more sensitive marker of drug effects and developmental alterations in brain function" than the evoked brain response measures he had initially intended to use. "Thus, my first 'real' scientific challenge as a Ph.D. resulted in my turning to sleep physiology as the primary focus of investigation," he says, the results of which were published in the journal Science in 1980.
   Dinges joined Penn as a post-doctoral fellow in 1977, attracted by the opportunity to work and learn more about sleep in the laboratory of Dr. Martin T. Orne, now emeritus professor of psychiatry, and the availability of affordable housing for himself and his wife Christine. "Both reasons for coming to Penn proved correct," Dinges says. His tenure with the lab he now directs "has lasted more than 20 years, and has been highly productive scientifically. Christine and I fell in love with Philadelphia, with Penn, and with southern New Jersey beaches. I have never regretted these decisions a day in my life."
   Penn today boasts one of the country's largest, most productive and internationally recognized communities of scientists and clinicians studying sleep, sleep disorders and circadian biology, Dinges says, crediting both his "outstanding colleagues" and the "bold and visionary leadership" of the medical school. "From a biomedical-research perspective in general, and a sleep-research perspective in particular, the University of Pennsylvania School of Medicine has been the place to be in the 1990s. There is no sign that this will change as we collectively cross into the next century."



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