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.
AWAKENING
TO SLEEP AS A SUBJECT
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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