Hello listers,
Today's NY Times carries a fascinating article detailing some
myth-shattering research about what can really set the human sleep cycle.
For some years now, mounting evidence seemed to suggest that the brain's
production of melatonin, a slee-regulating hormone, was governed by the
time and intensity of light hitting the retina. Since many blind people
lacked such an ability, it has been thought, this might help to explain
sleep disturbances some researchers say are overly-common among us.
Now comes this report, which suggests there may exist another mechanism
entirely which can regulate sleep -- and may send many researchers back to
their laboratories. It will be an interesting field to watch.
--Bryan Bashin
---------- Forwarded message ----------
January 16, 1998
Study Suggests Light to Back of the Knee Alters Master Biological Clock
By SANDRA BLAKESLEE
I n an experiment from the strange but possibly true category,
scientists have shone a bright light on the backs of human knees
and, in some mysterious way, reset the master biological clock in
the human brain.
Those treated with the light had their biological clocks advanced
or delayed up to three hours, enough to overcome the fatigue
associated with familiar forms of jet lag or insomnia. Why shining
light on the knee would have this effect is a mystery.
The finding is so surprising that many experts said they were
withholding judgment until the experiment was done again. But those
who heard the study described at a meeting last summer said it was
carefully done.
"We were all flabbergasted," said Dr. Michael Menaker, a biologist
at the University of Virginia in Charlottesville. "For three days
we tried to find flaws in the experiment and we couldn't."
Dr. Al Lewy, an expert on circadian rhythms at the University of
Oregon Health Sciences University in Portland, said: "We've taken
it as received wisdom that such effects would have to be mediated
through the eyes. I am very surprised. It is so revolutionary."
Dr. Thomas Wehr, chief of the clinical psychobiology branch at the
National Institute of Mental Health in Bethesda, Md., said: "There
are more biological mechanisms underlying the human response to
light than was dreamt of in our original hypothesis. Still, until
others repeat the experiment, the findings have to be regarded as
preliminary."
If the finding does hold up, the experts said, it will have
profound implications for basic biology, overturning conventional
ideas of how biological clocks are set. It may also lead to new
treatments for seasonal depression, sleep disorders and jet lag.
Airline passengers could wear a knee brace with a light source that
would reset their biological clocks as they slept during the
flight.
The study, which is being published Friday in the journal Science,
was done by Dr. Scott Campbell and Dr. Patricia Murphy of the
Laboratory of Human Chronobiology at Cornell University Medical
College in White Plains, N.Y.
When life began, primitive creatures needed to have a way of
keeping time and of knowing when it is light or dark, Campbell
said. And so they evolved a variety of internal biological clocks
-- cells or clumps of cells that oscillate every 24 hours, sending
out signals that control a host of behaviors such as when to wake
up, go to sleep, eat, mate, hibernate and the like.
Some creatures have light sensitive cells on various parts of their
bodies that help regulate the master clock. Horseshoe crabs have
clock sensors on their tail, swallows have them just inside their
skull and, according to a recent finding, fruit flies have
time-keeping genes active in their legs, wings and hair bristles,
suggesting that the entire body helps keep track of time. Because
day length changes through the seasons, every animal has to reset
its clocks every day.
Humans are thought to possess a single master clock in the brain
that "gives temporal organization to everything that we do,"
Campbell said, "but no one ever imagined we had light sensitive
cells on any part of our bodies" outside of the eye.
Even the eye presents a mystery, he said. It contains special cells
that gather light and enable vision. But these cells, called rods
and cones, have nothing to do with resetting biological clocks.
Many blind people experience jet lag, suggesting that other as yet
undiscovered light sensitive cells in the eyes are sending
important information about day length to the brain. Despite years
of looking, no one has ever found such cells in the eye.
"We thought we should look on the skin," Campbell said. An
experiment done a decade earlier by Wehr had found that a couple of
people with winter depression got better when light was
administered to their face, arms, legs and not to the eyes, he
said. "Dr. Wehr said it was so interesting that someone should
someday repeat the experiment," Campbell said. "So we did."
Fifteen volunteers came to the laboratory for four days and nights.
On the first night, researchers determined each person's biological
rhythm using two standard measures: body core temperature and the
rise in a hormone called melatonin.
"Your body temperature rises throughout the day and begins to
decline around 7 or 8 o'clock at night," Campbell said. It falls to
its lowest point about 5 or half past 5 in the morning and slowly
starts to go up again. In a similar vein, melatonin begins to
increase around 10 p.m. and makes people feel sleepy. It falls off
again during the day.
On the second night, the subjects stayed awake in a dimly lighted
room, reclining in a chair with a table over their laps. A thick
black material was draped over their legs and fastened to their
waists. Underneath this skirt, a knee pad with a fiber optic tube
was attached to the back of their knees and a bright light was
delivered through the tube for three hours.
Previous experiments with bright light delivered to the eyes showed
that it is possible to advance or delay the body clock depending on
when the light is given, Campbell said.
In the new experiment, subjects received light behind the knees at
various times between midnight and noon, Campbell said. For
example, one man got the light treatment between 1 and 4 a.m. and
another between 6 and 9 a.m.
Other subjects were put under the same dark skirt, kept awake the
same amount of time and given the same instructions. But
researchers did not turn on the light source. Neither group knew if
it was getting the light treatment or not.
On the third and fourth nights, all subjects were told to stay in
bed from midnight to noon and were allowed to sleep as their
biological rhythms were measured. In similar experiments done with
light to the eyes, body clocks are unstable on the third day and
this was also the case with light to the knees. The fourth day was
a surprise. For those treated with light, the timing of their
minimum body temperature shifted by up to three hours. Those
getting the sham treatment experienced small but statistically
insignificant changes in their bodily rhythms, Campbell said.
"This is the first demonstration that you can affect the human
clock without going through the eyes," Campbell said. "We assume
that somehow a message is getting from the back of the knee to the
master clock" in the brain.
How this happens is a major challenge to biologists. It could be
via skin cells, which are sensitive to light. But how the message
would get back to the brain is puzzling.
Dr. Dan Oren, a researcher at the Yale School of Medicine in New
Haven, Conn., recently suggested a daring hypothesis involving
blood as a carrier of the light signal. Hemoglobin responds to
light in much the same way that chlorophyll does in plants, Oren
said, and chlorophyll regulates plant circadian rhythms. Moreover,
hemoglobin carries nitric oxide, a neurotransmitter that could
carry information about day length to the master clock in the
brain.
The back of the knee happens to have many blood vessels but it is
usually covered by clothing, Oren said. Another place rich in blood
vessels is the retina. Thus the time sensitive cells that everyone
has been looking for in the eye might not be cells at all; they
could be hemoglobin molecules.
The finding may have practical applications. People with winter
depression often have to rise before dawn to look into a light
source to alter their biological clocks, Campbell said. Now they
might get the light treatment while they sleep.
And, when flying to Paris, Campbell said, "With a light to the back
of the knees, you could sleep while your clock is being shifted and
wake up in the new time zone, ready to go."
Home | Sections | Contents | Search | Forums | Help
Copyright 1998 The New York Times Company
This archive was generated by hypermail 2b29 : Sun Dec 02 2012 - 01:30:04 PST