RESPONSE TO LIGHT
by John M. Ott, taken
from his book, Health and Light
All of my research, plus external information that came to me from many
sources seemed to indicate, more and more, that animals respond to the
intensity, periodicity and wavelength distribution of light in much the
same way that plants do. Certainly there was sufficient additional evidence
to warrant submitting another grant application to the National Institutes
of Health. Several doctors prominent in research work wrote letters of
recommendation to Dr. James Shannon, Director of The Public Health Service
of The National Institutes of Health, resulting in his taking a personal
interest in our effort and offering some guidelines to follow in submitting
the next grant application. Six of the doctors, including several members
of our Board of Directors, agreed to act as collaborators and actively
participate in the project. They all helped in preparing the forms for
The six doctors included Robert Alexander, M.D., Chief Pathologist, Presbyterian
St. Luke's Hospital, Chicago; Samuel Lee Gabby, M.D., Senior Member of
the staff and member of the research committee, Sherman Hospital, Elgin,
Illinois; Elliot B. Hague, ophthalmologist and Chairman of the New York
Academy of Sciences Conference on "Photo-Neuro-Endocrine Effects
in Circadian Systems with Particular Reference to the Eye;" living
H. Leopold, M.D., ophthalmologist, Director of Wills Eye Hospital, Philadelphia:
Frank J. Orland, D.D.S., Director of the Walter G. Zoller Memorial Dental
Clinic, of the University of Chicago, where we had previously assisted
with an experiment that showed a relationship between the amount of tooth
decay and the type of light environment that laboratory animals were
(mentioned in Annals of Dentistry, Vol. XXVII, No. 1, March
1968, Page II), and Edward F. Scanlon, M.D., member of the staff and
Head of the Tumor Research Committee of the Evan-ston Hospital in Evanston,
Meanwhile, I was invited to speak before the Sarasota County Medical
Society and show the time-lapse pictures. Shortly thereafter, Dr. Thomas
G. Dickinson, who had originally put me in touch with the Wills Eye Hospital,
held a special meeting at his home and invited other doctors who had
indicated their interest in our light experiments. One of the doctors
was Roscoe Spencer, M.D., who had recently retired as Medical Director
of the United States Public Health Service, where he had been in charge
of cancer research. He wrote a strong letter of recommendation to the
new Director of the National Cancer Institute, Dr. Kenneth M. Endicott,
urging that favorable consideration be given to our currently pending
grant application. A month later a letter advised us that the National
Advisory General Medical Sciences Council did not recommend approval
of our application. Upon our request for specific reasons, we were informed
Our reviewers carefully examined your proposal to investigate biological
responses to specific action spectra. They observe that no details
of the experimental design are given; current literature on photobiology
is casually mentioned, and pilot experiments are referred to but
not adequately described. Finally, this vague proposal gives no
of a basis in scientific fact or method. They further commented
that it is not known that the applicant has any specific background
would permit him to analyze physiological phenomena in a meaningful
and that the six persons named as collaborators have impressive
titles and affiliations, butnothing is offered in support of their
to participate in the project.
Chalk up one more disappointment and a big one this time. It was a
real letdown to have to stop thinking about plans for an expanded
research program and to get down to the realities of making the
most of our
limited facilities and finances.
Despite this handicap, we began to study the effect of different
colored light environments on mice. It had been necessary to start
breeding colony of rabbits for the pigment epithelial cell experiment.
wasn't any available space to accommodate the larger rabbit cages,
so the only solution was to push aside some of the time-lapse projects
plants to make way for the rabbit cages. I soon found that the results
we were obtaining in breeding rabbits in the ultraviolet transmitting
plastic greenhouse were so far superior to the average results obtained
in artificially-lighted animal breeding rooms that the delay of the
time-lapse sequences involving plant studies was more than offset.
I began thinking about the results of adding a little long wavelength
or black light ultraviolet to the ordinary incandescent light source
of the microscope and it seemed to me to be quite significant,
especially when coupled with the exceptionally satisfactory results
in the breeding of rabbits in the ultraviolet transmitting greenhouse.
This prompted me to build additional space where laboratory animals
be exposed to natural sunlight conditions through different types
glass and plastic materials that would allow various amounts of
natural ultraviolet to penetrate. The additional space also contained
with a simple air curtain that would allow the natural sunlight
to penetrate unfiltered in any way. The opening was screened to keep
insects out and the air was circulated
from the center of the animal room through the various compartments
and out the air curtain, in a way that would keep the cold weather
The improved results in breeding not only the rabbits in the ultraviolet
transmitting greenhouse as compared to the standard artificially-lighted
breeding room, but also the differences noted in breeding both mice and
rats under the air curtain as compared to the various colored light compartments
were almost unbelievable. In breeding laboratory animals it is standard
procedure to remove the male from the cage before the litter is born
because of his tendency toward cannibalism. However, the male rats in
cages exposed to sunlight through ultraviolet transmitting plastic, quartz
glass or air curtain were observed to help care for the litter, especially
when the female was removed from the cage. Furthermore, the adult male
rats appeared decidedly more docile and friendly when handled, whereas
those kept under fluorescent light seemed more irritable and developed
a tendency to bite.
Although these results were interesting, the numbers of experimental
animals did not approach statistical significance. However, later experiments
involving larger numbers of animals did begin to show significantly different
responses when kept under different colors or wavelengths of light.
In a group of 536 mice born under the air curtain, ultraviolet transmitting
plastic or quartz glass, all except 15 survived to maturity. This represented
a survival ratio of 97 per cent. Under various types of fluorescent
light 88 per cent of 679 mice survived to maturity. Approximately 94
survived to maturity under cool white, warm white and daylight white
lamps, but the percentage of survival noticeably declined under the
different, deeper-colored lights. The lowest survival rate of 61 percent
occurred in the mice exposed to pink fluorescent light.
The animals being kept outdoors under natural sunlight corning through
ordinary window glass, ultraviolet transmitting plastic, quartz glass
and the air curtain, also showed significantly different responses. The
tails of both male and female C3H mice became spotted and would develop
sores under 12 hours daily exposure for three months to pink fluorescent
light. At this stage of development, when some of the mice were transferred
back to the air curtain, the tails would again appear normal after thirty
days. If, however, the mice were left under the pink fluorescent for
six months, the tails would appear gangrenous and, bit by bit, slough
off until some of the more severe conditions resulted in complete necrosis
of the tail. A careful examination of this tail condition revealed no
evidence of the presence of any bacteria or fungi.
A subsequent showing of the mice pictures brought the following letter
from Phyllis A. Stephenson, M.D., who is now a member of our own Medical
and Scientific Advisory Board.
March 2, 1970
Dear Dr. Ott:
As a practitioner of medical oncology, and having spent two years in
research in tumor immunology, I have noted particular difficulty with
two strains of mice at our laboratory at the Sloan-Kettering Institute.
One is the C3H mouse, the other the SJL/J mouse, as far
as the tail lesions are concerned. Multiple attempts to find the
etiology of this
made at the Jackson Memorial Laboratory, our own particular laboratory,
and others. No definitive cause has been found: no good article is
in the literature. It has been felt that bacterial infection (streptococcus?),
humidity and overcrowding does contribute to these particular lesions.
However, placing the animals in cages with smaller numbers of others
and giving them forms of activity
such as a running wheel did not significantly lower the incidence
of lesions. It is significant that these tail lesions alone have
known to decrease the nutrition of the mice sufficiently to eliminate
from significant laboratory experiments. Multiple microscopic sections
and cultures for bacteria and fungus from the lesions of these mice
find only an irritative phenomena in filtration of white cells and
into the area affected, with no constant bacteria or fungus. Autopsy
of these mice show no internal tumor process. The lesions become
so bad that the mice lose their tails, with infection at the stump
invades the rectum, causing an obstructive type of situation The
mouse becomes completely debilitated and may die.
In my experience we have never used any different mode of lighting
for its work-Up. Most of the time these mice are sacrificed by the
laboratory which bought them. We did consider the tail lesions a major
problem in our laboratory. These two strains of mice are used commonly
in research: the SJL/J for lymphoma and leukemia studies (TL 1,2,3,
positive) and the C3H for mammary tumor and Gross virus
studies. It is interesting that other mice do not consistently develop
lesion. It may be specific for the inbreeding of these two strains.
Specific treatments such as topical and systemic steroids, topical
and systemic antibiotics did not help. The SJL/J mice are very active,
nervous mice which are known to occasionally attack each other. However,
the C3H Bittner is a relatively docile animal and we cannot
correlate the temperament of the animal with the tail lesion. Thus,
I feel that
the tail lesion is a significant problem with mice in the laboratory
setting and any answer we could find would be extremely helpful.
Phyllis A. stephenson, M.D.
We were trying to find some of the answers
ourselves.Three months exposure of the same C3H strain
of mouse during the daylight hours to a new purple,
plant growth fluorescent tube would result in the animals losing
much of their fur, and after six months under the purple light they
lose almost all of their fur and appear to be in a relatively unhealthy-looking
condition. Autopsies performed on some of the animals indicated a
normal, healthy condition of the heart tissue in all those from the
compartment, whereas all those from the pink fluorescent light showed
an excessive condition of calcium deposits known as calcific myocarditis.
The tails of the mice under the pink fluorescent light and the fur
of the mice under the purple light were of course exposed directly
lights. The abnormal responses may therefore have been due to the direct
exposure of the tails and the fur to the light, or possibly these results
could have been due to the light entering the eyes and stimulating
the retinal or oculo-endocrine system which may control the body chemistry.
However, the heart tissue is not directly exposed to the light and
results must therefore be mediated in some indirect way, possibly through
the eyes and pathway to the endocrine system.
In a simple preliminary experiment, the cholesterol level in the blood
of mice kept under dark blue fluorescent light was found to be higher
than in the blood of mice under red light. Many of the male mice under
blue light became obese; this tendency was not noticed in the females.
These inconclusive observations are mentioned only to suggest the extent
to which light might possibly be a variable in such research studies,
and again, they emphasize the need for positive scientific control
of all light sources used in the laboratory. Consideration might also
given to establishing some standard color for walls, ceiling and floors.
In the October 25, 1963, issue of Science, the effects of isolation
stress on white rats was reported. A marked difference in the toxicity
community-caged rats and isolated rats provided a criterion for following
the development of isolation stress. According to this group of investigators,
the reversibility of isolation stress was also established, the reversal
being attributed to the effects of short term versus long term isolation.
Short term isolation stress was defined as one to ten days and long
term from ten to thirty days. My particular interest in this article
on the reported condition of caudal dermatitis, or scaly tail,
which also followed a reversibility pattern attributed to the short
versus long term isolation stress. Although this condition was not
serious as the condition of the tails of our mice under the pink fluorescent
light, the similar reversibility patterns were definitely of interest.
Of course the condition of complete necrosis of the tail could not
be reversed, but during the early stages of development it seemed quite
definite that the reversibility was attributable to the mice being
from the pink fluorescent to the full natural sunlight received through
the air curtain.
My interview with the principal investigator in charge of the isolation
stress study, and all of his co-workers, revealed that coincidentally,
at the precise time between that designated as short term and long
term isolation stress, the lighting environment of the two groups of
was drastically changed. All the cages containing the isolated animals
were on one large rack at one end of the animal room, with the cage
doors directly facing the windows. The colony groups of animals were
similar rack in a dark area and with the cage doors facing away from
the windows. During the interview, it was learned that one of the laboratory
assistants had moved the racks when mop-ping the floor and had inadvertently
switched their locations. Needless to say, this emphasizes the need
for having laboratory light sources under scientific control.
Continuing with our experiments with the C3H strain of mouse,
which is so highly susceptible to spontaneous tumor development,
our purpose was
to carry out further experiments to determine the length of time
required for such tumor development in the animals kept under different
environments. This part of the experiments did, I believe, reveal
possibly the most significant data of all of our experimental work.
The C3H strain of mice kept under pink fluorescent light
developed spontaneous tumors
and died, on the average, in 7 1/2 months. The animals under different
types of light with an increasingly wider spectrum showed a progression
in life span up to 16 1/10 months. Over 2,000 mice were used in this
Click to enlarge
It is interesting to note that the most extreme adverse
conditions regarding not only tumor development but also necrosis of
in the heart tissues, smaller numbers in litters, and difficult behavioral
problems, all were caused by pink light.
The question then arises that if these responses are due to the absence
of the shorter wavelengths and the influence of the longer wavelengths,
why then are some of these responses not most severe under red light—as
in the case of the chloroplasts in the cells of Elodea grass? The
answer to this is not clear, but consideration might be given to
that many nocturnal animals do not see red light because these wavelengths
are beyond the range to which their visual receptor mechanism is
responsive. Many zoos are now using red light in rooms where nocturnal
located, and the animals seem to think it is nighttime and are accordingly
more active and interesting to watch. When ordinary lights are turned
on the animals usually curl up and go to sleep.
The indication that some nocturnal animals cannot see red light,
and the suggestion that other nocturnal animals can "see in the dark" because
their eyes are sensitive to infrared is somewhat contradictory.
However, the range of wavelengths to which the visual receptors of
nocturnal animals respond may vary with different species. Likewise,
receptors may not respond to the precise same range of the longer
wave lengths that activate the oculo-endocrine system, which seems
definitely so with the ultraviolet.
The results of the spontaneous tumor development experiment under
different types of lights were indeed quite startling, and several
in cancer research who had assisted in setting up the proper controls
for our experiments agreed that this experiment should certainly
be repeated, and several agreed to do so at the various hospital
with which they were associated.
Dr. Samuel L. Gabby, who had conducted the expert -ment with the
mice in his basement, offered to keep some outside as well if we
him some sort of portable enclosure with an ultraviolet transmitting
cover. We did, and he obtained virtually the same results as shown
in the tumor development chart.
I was also asked to show the films and speak at one of the research
seminars at The Evanston Hospital, north of Chicago, where Dr. Edward
one of our trustees, was head of the Tumor Research Committee and
had been named as principal investigator in our last N.I.H. grant
Immediately following my presentation. Dr. Scanlon advised that work
was actually in progress in injecting hamsters with several different
tumor transplants in connection with their studies of the effectiveness
of various anti-tumor drugs. He suggested that they would postpone
the injection of the drugs for the time being if I would take half
animals, selected at random, and keep them in the air curtain compartment
in our laboratory animal quarters where they would be subjected to
natural daylight. The other half would remain in their regular laboratory
under cool white fluorescent tubes. This plan was agreed on.
Dr. Scanlon and several members of his staff periodically visited
our laboratory as the project proceeded. The results of this experiment
showed that the animals that had received a very fast acting tumor
showed little difference in the life span from those under the air
curtain and those that remained in the regular animal laboratory
the hospital under cool white fluorescent tubes. However, those animals
that received a slower acting type tumor transplant did show a significant
difference. The animals remaining under the cool white fluorescent
tubes showed an average life span of 29 days, whereas those kept
air curtain averaged 43 days.
With the unanimous approval of the entire
research committee of the hospital. Dr. Scanlon wrote a report, together
with a request for a small
research grant to carry on further studies, and submitted this to
the Illinois branch of the American Cancer Society. The Illinois branch
in turn forwarded the report and request on to the American Cancer
headquarters in New York City, and in due course the following reply
was received from the Illinois office:
In a memorandum under date
of December 9 we have received information
from the Assistant Vice President for Research at National that the
Advisory Committee has recommended disapproval of this application,
with the following
It is proposed to study the effects of visible and near-visible light
on the growth of transplantable hamster cancer in hamsters, by exposing
inoculated animals to various bands of the spectrum and following
the animals through their life spans.
It should be noted that the assay—life span—is a summation
of a host of factors not necessarily connected directly with tumor
behavior per se. The results will be difficult or impossible to interpret
meaningful way. Any direct effect of light on tumor cells cannot be
observed in this study and no evidence exists or is presented to warrant
that such exists. No account is taken of the penetration of visible
and near-visible radiations into the animal or the tumor cells, nor
and photochemical effects (e.g. burns); statistical precision for meaningful
correlations will be insufficient.
While there is every likelihood that exposure to different kinds
of light will affect certain physiological response in the animals,
will only confuse the issue.
Support of this proposal and project as presented is not justified
on scientific grounds.
The power and authority of such a distinguishedscientific
committee is awe inspiring. There is no recourse. Their word is final.
combined knowledge and wisdom is supreme. But how can anyone be
so certain as
to what cannot cause cancer until it is known what does? To say
that considering light as a variable would only further confuse the
is difficult to reconcile with the basic concepts of research.
Being turned down again was discouraging, to say the least, but
none of the reasons yet given by any reviewing committee has offered
convincing evidence that light energy might not be a missing link.
In fact, all
of the reasons given opposing the suggested light hypothesis indicated
to me a great need for additional and determined pursuit of the subject.