New light shed on supposed blind "abnormality"

From: Bryan Bashin (bashin@calweb.com)
Date: Sat Jan 17 1998 - 00:19:50 PST


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."
     
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