TPC NEWS Vol. 3, No. 1 , Spring
1984 (Wholoe Number 5)
(English
Summary) (Revised Edition)
Page-3
Essay: Animal experiments and
animal protection
Recently, we often hear that the criticism and movement against animal
experiments, especially against the one using nonhuman primates, have risen in
various parts of the world. For
instance, it has been reported that some of the regional primate research
centers in the U.S.A. were attacked by the demonstrators of such opposition
movement last spring. In Japan, we
have hardly heard that kind of movement yet, but I think we must not look on the
situation in foreign countries with utter indifference.
That is: we have to listen to what the opponents say in order to judge
whether they are appropriate or not, and have to engage properly in daily works
and studies.
By
the way, it seems that there are two main tendencies in those opposition
movements against animal experiments using nonhuman primates.
The first one is, from the view point of the conservaition of nature, to
protest strongly against various human activities which may bring a decrease in
wild monkey population. Those who
hold this view point protest against the experiments in which wild-originating
monkeys are used, but they do not oppose to the experiments using
domestically-bred nonhuman primates. The
second current of the opposition campaigns is to protest throughly and
completely against all kinds of the experiments which give pain and suffering
such as restraining to monkeys. Sometimes
these two currents join together, resulting in a stronger tide of opposition
movement.
Those who work with nonhuman primates as laboratory animals have a good
understanding about the first concept of the opposition movemets.
Nowadays, scientists and scientific autholities in many countries are
making effort to establish domestic breeding systems for laboratory primates.
On the first step of that establishment, however, they must procure and
maintain a great number of wild-originated monkeys as breeders.
This situation itself is, more or less, contradictory to the first
standpoint. Moreover, there is
another problem that it will not immediately be materialized that all of
nonhuman primates for experiments are provided from the domestic breeding
source. On the other hand, it
is quite natural that we don't agree with the views advocated by the second type
of opposition movements. Of course,
we know enough that the spirit or activities of animal protection are very
important for the aesthetic or cultural side of human life.
However, it is not until we are in good health that we are able to give
enough consideration to the life or existence of animals including nonhuman
primates, I wonder. There are
probably few people who can continue to love animals when they are ruining their
health, with some exceptional cases. Any
way, we must solemnly be aware that we, ourselves, are the living creatures
which have been so evolved that they can not live in health without sacrificing
many kinds of animals. Extending
this way of thinking, therefore, we have to do experiments using animals instead
of human beings in medical and biological research fields. If experiments using humans are done with skipping of animal
experiments, the problem will become more serious. I wonder, how radical animal protectionists protesting
against all kinds of animal experiments think about this point?
Be
that as it may, even today, some of the Japanese scientists participating in
animal experiments donft care about that we must carry out the experiments
with an attitude of moderation. As
every one knows laws and regulations such as The Law of Animal Protection and
Care( October 1, 1973, Law No. 105), The Regulation of Feeding and
Maintenance of Laboratory Animals (March 27,
27, 1980 Notification No. 6 the Prime Ministerfs Office), and Guidelines
for Animal Experiments (November 5, 1980, Recommendation of Japan Science
Council) are in full force in Japan. Those
who are concerned with animal experiments should correctly understand the
fundamental spirit of these laws and regulations, and should conduct their works
with a great gratitude for animals, responding to the appropriate criticism of
animal protectionists, I think.
Page-4
Breeding Topics:
Unusual Presentation as a Cause of Stillbirth
Needs for nonhuman primate of better quality as laboratory animals will
become larger and larger in the future. So
we should be eager to establish more efficient breeding techniques.
After the establishment of TPC we have bred more than 1500 cynomolgus
monkeys of good quality. To our
regret, nine percent of 1500 were stillbirth.
Dr. A.G. Hendrickx of California Regional Primate Research Center in the
U.S.A. has summarized that the ratio of stillbirth in breeding colonies of 11
primate species which appeared in 7 different papers ranged from 5.9 to 20%.
Recently we have found one of the direct causes of stillbirth.
As
an item of health check-ups for the pregnant monkeys of late gestation period,
we have recently made it a rule to palpate their fetal presentation every day
after 155-days of gestation. We
have already performed the serial check-ups with 340 pregnant monkeys, so far. The
relation between the fetal position on the day before delivery and the incidence
of stillbirth was shown in the table. Thirty-three of the 340 pregnant monkeys underwent Cesarean
operation for various experimental purposes.
Two handreds and seventy-five of the remaining 307 pregnant females who
made natural deliveries showed cephalic presntation on the day before delivery.
Only one (0.4%) of the 275 monkeys brought stillbirth.
On the other hand, out of 32 monkeys who showed breech presentation on
the day before delivery, 21 monkeys (65.6%) brought stillbirth.
We
consider, on the bases of these results, the breech presentation is not only an
abnormal fetal position but also one of the valid causes for stillbirth.
Now we are surveying whether or not there are female breeders who show
abnormal presentation in every pregnancy, and the relationships between the do
fetal presentation and weight, gender or gestation length of newborns.
Page-5
Hematlogical and Biochenical Examinations in Periodical Health Inspection
Our monkeys undergo periodical physical inspections once a year after one
year of age. The inspections
consist of such items: observations of general health conditions and ocular
fundus, bacteriological examinations of stool, cerological tests for antibodies
against some viruses and hematological examinations.
The routine items of the hematological and biochemical tests are: red
blood cell count (RBC), hematocrit value (Ht), hemoglobin content (Hb), mean
corpuscular volume (MCV), white blood cell count (WBC), erythrocyte
sedimentation rate, two kinds of transaminase (GOT, GGPT), serum total protein (TP),
serum albumin (ALB), blood glucose (BGLU), blood urea nitrogen (BUN), total
cholesterol (T-chol) , free cholesterol (F-chol), tri-glyceride (TG) and serum
alkaline phosphatase (ALP). We
carry out these tests with 60 to 70 animals once a week
by using an automatic blood-cell counter and an auto-analyzer.
About 7 m1 of blood is taken from every monkey for these tests and
aliquot of the taken blood is kept serum-bank
Needless to say, hematological and biochemical values differ with animal
species, ages, sexes, breeding conditions, etc.
As the periodical inspeotion was set only four years ago, now we are just
at the first stage of knowing about hematological and biochemical values of the
cynomolgus monkeys bred and raised under the artificially controlled
environments. Parameters pertaining
to red blood cell such as RBC, Ht and MCV obviously showed the difference in
value with age and sex. The
activity of ALP showed a great change with growth.
The change of serum lipid value in pregnant female monkeys has an
important meaning for breeding. Generally,
T-chol and TG of pregnant female monkeys showed low lovels until delivery,
unlike humans.
We
can also use these values for screening of abnormal animals.
Especially, blood sedimentation rate is a useful parameter to find out
ill health conditions such as anemia and hypoproteinemia.
By
the way, another purpose of the periodical inspection is to check the invasion
of infectious diseases into our breeding colony.
Fortunately, we have no experience of infection accident yet.
I think that the hematological and biochemical tests are necessary and
important as the first step of checking the suspected cases of some viral
diseases such as viral hepatitis, etc. (Data
of male cynomolgus monkey aged 5 years are shown in the table .)
Page-6
Introduction of the Equipments: Television system
We have adopt a special TV system in order to observe our 2200 monkeys
kept in about 40 animal rooms of five different buildings.
A TV camera is set in every animal room.
It can be put on any place in the room as far as the cord of camera
reaches. Six monitor TV sets with a remote control board, a long time
video tape recorder and a video printer are installed in the corner of
animal technicianfs room. Observers
can choose any TV camera they want, and get pictures on any monitors.
The room they can watch at a time, however, is limited to six in number.
TV cameras used in the behavior observation room are set on two rails in
the camera house placed in front of the monkey cages as shown in the photograph.
The cameras can follow the movement of monkeys through the window of
deflection glass without attracting monkeyfs attention.
The front glass of monkey's cages is made of reinforced glass and fitted
not vertically but aslant in order to avoid light reflection disturbing the
clear pictures on the monitor.
Using this TV system, we can observe not only the conditions of the
monkeys undergoing surgical operations or anesthesia but also their behaviors of
delivery, nursing and mutual relations of infant monkes of group feeding.
Sometimes these TV sets bring us interesting and unexpected discoveries
with monkeysf behaviors .
Page-
7 On the Techniques of Care and
Management of Cynomolgus Monkeys
Notions
used in animal rooms- Clothespins and colored card
It is impossible for us to memorize daily health conditions of all
monkeys kept at TPC. So we use
clothpins and colored cards, which are put on the front of the cages, to mark
health conditions. Usually,
clothespins of five different colcors, red, yellow, blue, orarnge and brown are
used. Red one means a female monkey
with menstrual or postpartum bleeding. Since
the cynomolgus monkeys ovulates regularly about eleven
days after the first day of menstruation, observation of their
menstruation is so important for successful breeding.
Yellow one is put for consecutive three days after the end of
menstruation: and the direction of the pins has meaning as follows: left---the
first day after the end of mense, center---the 2nd day, and right---the 3rd day. Blue clothespin indicates a monkey suffering from diarrhea,
meaning also not giving fruit such as apples and oranges in the morning.
Banana containing a dose of medicine is given to the monkey of the blue
pin in the afternoon. Orange one is put to indicate a monkey having no appetite and bing in bad nutritional conditions.
The monkey also is given banana in the aternoon.
Brown clothespin is used only for the case of an outbreak of specific
diseases ( Nasal bleeding of unknown cause once occured.)
Colored cards are put into the card case of animal raunber.
Mainly, red, orange and blue cards are used. Their meaning are as
follows; Red card---pregnant monkey the date of delivery is filled in.
Orange card---monkeys being in medical treatment, in serious cases the
hem of the card is colored with a red felt-tip pen. Blue card---monkeys given
anesthetic drugs.
Page
8 A case Report: Anatrichosomiasis
in cynomolgus monkeys
Parasitic diseases of nonhuman primates are generally classified into two
main categories according to the parasite, which is transmissible to man or not.
Needless to say, the first one is hazardous not only to nonhuman primates
themselves but also to personnels working with monkeys.
The studies of the second category have an important meaning from the
view point to improve the quality of nonhuman primates as laboratory animals.
This case, Anatrichosoma sp. infection, is supposed to be the first
report in Japan.
It has been reported that
Anatrichosoma is parasitic in the nasal mucosae and skin of several primate
species. In human cases the
parasite brings sclapping disease. As
for the cynomolgus monkey,
parasitism A. cynomolgi has been reported.
But its pathogenicity, significance for public health as well as its life
cycle are hardly known yet.
The present case was
found in the process of pathological inspection for minute nasal bleeding of
unknown cause.
The parasite was found in the epidermis and dermis of itestibulum nasi.
The tissue surrounding the parasite was pressed and degenerate.
The epidirmis was obviously hyperplastic.
Parakeratosis and bleeding were recognized on the surface of the
epidermis . In the dermis, slight
infiltration of plasma cells and easinophilic cells, in addition to giant cells
and round cells were observed around the parasite.
Bacillary bands were recognized in the cross section structure of the
parasite in the lesiorn. The ova of the parasite were yellow brown and its shell
was thick. Its size was 72 .5
(60-80) x 44 (35-55)Ę,
and larva was observed in it.
After the discovery of this case, the examination for the presence of ova
was carried out by swabbing the nasal cavity muscoase with 140 wild-originated
cynomolgus monkeys. As a result,
two of 50 Indonesian monkeys , one of 40 Philippine monkeys were positive.
All 50 Malaysian monkeys were negative .
It can be considered that this parasite has some relation to minute nasal
bleeding of unknown cause from which our cynomlgus monkeys sometimes have
suffered.
Page-9
A Comment on Our Research:- Ophthalmoscopic observations of the ocular
fundus in colony-born cynomolgus monkeys
Examination of ocular fundus is not only a way for diagnosis of ocular
diseases but also a useful item of clinical examinations relating to systemic
diseases. In this note I will mention some of the experiences which I
accumulated in the process of the ocular fundus examination in our cynomolgus
monkey colony.
This survey will come to
an end in May, this year, but I think that the end is the first step to our
ophthalmoscopic studies of the cynomolgus monkeys .
Someday we will have been able to collect more than three thousand
pictures of ocular fundus of the cynomolgus monkeys as laboratory animals.
1)
Normal findings of ocular fundus in different age classes
When we started this examination, there were already several reports
about normal or abnormal ocular fundus of nonhuman primates, but there were no
report regarding the cynomolgus monkeys . Then
we thought that it would be very important for the judgement of abnormal
findings to establish criteria for normal ophthalmoscopic findings in healthy
monkeys whose ages were exactly known. In
those days, a lot of cynomolgus monkeys aged from 0 day to 20 years were fed at
TPC. So an experiment was planed to
obtain normal ophthalmoscopic pictures, using about twenty monkeys each in
different age classes ; 0-day-old neonate, three months old, one year old, three
years old, 5-7 years old, 15 years old and 19 years old.
The examination for the 0 day old monkeys was first tried, but I learned
it was so difficult to open their eyelids.
So, we had to change our plan. Old
aged animals might suddenly die, but new babies were born almost every day.
We thought we had better to begin the examination with the older animals.
This change of examination-order, however, caused delay to meet
interesting discoveries which I am going to describe in the following
paragraphs. When we finished the
observations of the monkeys aged 1 to 19 years, we thought that there were no
significant difference in the findings of ocular fundus among monkeys of
different age classes. Of course,
we had recognized some minor differences, for example, gradual color changing
from blue green to brown with age increasing.
The retinal color showed blue green to brown, the optic disc color was
orange, the macular color was dark and the central pit was detectable clearly.
The diameter of retinal arteries around the optic disc was thin
(two-thirds of the veins). The
arteries were pale reddish and the veins were dark red.
The veins surrounding optic disc branched clearly to two directions up
and down, and some of the veins run through the both upper and lower sides of
the macular, drawing an arc (fig. 1). All
the pictures we had obtained until that time showed such colors and findings.
One day we examined ten three-month-old monkeys and a 0-day-old newborn
neonate according to our plan. We
had no new findings in the observation for three-month-old monkeys.
In the next examination of the 0-day-old monkey, however, his eyelid
could not be opened as once we had tried. . . . ., after a while, the figure of
his ocular fundus appeared clearly . . . . .
It resembled Albino 's ocular fundus : the color of the retina, including
the optic disc, was salmon pink, the macular was not seen clearly, vessells in
the chorioidea was generally transparent, since the pigmentation was not enough
in the retinal epithel. I was
confused for a moment. Do I have
found a case of congenital malformation that has no pigment in the eye?
Or otherwise, do all 0-day-old cynomolgus monkeys have these findings?
After all, it was proved by additional examinations of the 0-day-old
monkeys that the latter hypothesis was right.
Moreover, it was recognized that the retinal arterie's inside diameter
was about one-third of retinal vein's. The
investigations carried out with baby monkeys of different ages in weeks revealed
that there were remarkable differences in findings of ocular fundus, especially
in the color, with ages: the retinal color was salmon pink with the 0 to
3-day-old neonates, green was partly added with the l to 2-week- old animals;
with the 3-week-old monkeys the color completely changed from salmon pink to
blue green, blue to green with the 6-week to 2-year-old, blue to gray with 3 to
5-year-old, and brown with the monkeys more than 7 years old. As
regards optic disc, with the 0 to 2 weeks old monkeys were salmon pink, and with
those of the infants aged more than 4-weeks showed orange.
The retinal arteries were pale reddish and the veins were slightly dark
in color with the monkeys of every age class.
The macular was hardly distinguished in the 0-day-old neonates, but it
became slightly dark in the 3-day-old babies, and it became so dark as to be
distinguished after 2-weeks of age. The
retinal reflex was observable first in the monkeys aged more than 2-weeks, and
its peak was in the 1-year-old monkeys. Central
pit was detected in the monkeys more than 6-month-old.
In addition to these findings, we found another two interdsting findings:
retinal hemorrhages and persistent hyaloid artery in newborn monkeys.
2)
Retinal hemorrhages
As I previously mentioned, it was so difficult to open the eyelids of
0-day to 1-week old mankeys that we had to manage a method for taking good
pictures of their ocular fundus in focuse.
When I was examining those pictured, I usually checked them
within a week after the photo shooting, I noticed hemorrhagic findings
spreading in a line over the retina. I
exammined again some other 0-day-old monkeys' pictures and encountered the one
having clear hemorrhagic spot. Calculating
the incidence of such hemorrhages, I found that about 61% of 36 monkeys born
normally had retinal hemorrhage. The
hemorrhage appeared in various shapes such as spot, line and stain, in
one to ten or more per ocular fundus.
These retinal hemorrhages disappeared naturally by 3-days to 2-weeks of
age, showing the severest picture at 1-week of age.
We performed fluoro-funduscopy for some monkeys, and confirmed that the
hemorrhages occured in the retinal strata, and the bleeding had already stopped
by that time. In respect to the frequency of deliveries of their mother
monkeys, the incidences of retinal hemorrhage were as follows: 3(42%) of 7
monkeys with the first delivery, 8(62%) of 13 monkeys with the second delivery,
11(73%) of 15 monkeys with the third delivery and 0 of 4 with the fourth
delivery. There was no difference
related to the sex of infant in the incidence of retinal hemorrhage.
No significant relation was observed between the retinal hemorrhage and
the infant's birth weight.
Retinal hemorrhage has been detected in 30 per cent of human
neonates. Pressure given to the
head of the newborn in the birth canal during delivery is considered as one of
the causes. In addition, there is a
report, that retinal hemorrhages are found more frequently among the newborns
delivered by the use of a clamp or sucker and less often among the neonates born
by Cesarean section. Then, in
order to examine neonates for the presence of retinal hemorrhages we conducted
Cesarean operation using 30 pregnant cynomolgus monkeys at 154 to 174 days of
gestation age.
(See page 12 of "A
clinical commentary by a cub veterinarian") During the operations, we payed
attention as much as possible not to give pressure to the head of the fetus, so
we took out the uterus from the abdominal cavity pressing it lightly through the
abdominal wall by hands. As a
result of this investigation, it was revealed that the incidence of retinal
hemorrhage was about 33% of the 30 monkeys examined. This incidence was significantly lower than that (67%) of the
neonates born normally and the severity of hemorrhage was slighter in Cesarean
sectioned newborns than in normally born neonates.
Nevertheless, the fact
that retinal hemorrhages were still recognized in 33% of the Cesarean sectioned
neonates, though it was lower in incidence, suggested that there were another
causes besides the pressure given to the fetal head in the birth canal during
delivery. Since these hemorrhages
disappeared by about 1-week of age without exception, we considered that it was
not a pathological phenomenon in newborn monkeys in this period, we would like
to do further investigation to find out another cause of retinal hemorrhage.
3)
Persistence and disappearance of hyaloid artery
On the day of birth, persistence of the hyaloid artery was observed in
all of the neonates examined. We
could see the hyaloid artery with the naked eye by illuminating the crystalline
lens that was made to be mydriatic. Moreover,
during observations of the fundus, it was possible to see the hyaloid arteries
which run through the center of the optic disc and reach the crystalline lens.
The period of the disappearance of hyaloid artery varied with species of
animals. Two species, in which the
arteries disappeard at fetal stage and after birth, had been reported.
So we continued the longitudinal observation following the age in days of
infants, in order to make sure the disappearance period.
The examination was carried out twice a week, once every three or four
days, until no hyaloid artery could be observed in two consecutive observations.
The result was that the hyaloid artery disappeared at 4-weeks of age on
the average ranging from 3 to 6-weeks, without exception.
Then we concluded that the persistence of the hyaloid artery in the
newborns which disappeared during an early period of life was not a congenital
malformation nor an abnormal phenomenon caused by some causes, but a normal
physiologic phenomenon.
4)
Survey of all cynomolgus monkeys at this center
As I mentioned above, we obtained the following normal findings in
colony-born cynomolgus monkeys aged from 0 day to 19 years : marked change of
the retinal color during the period from the day of birth to adulthood, and
retinal hemorrhages and persistent hyaloid artery are seen in 0-day-old monkeys.
We began to examine all cynomolgus monkeys in this center.
Two animal technicians examined 20 to 30 monkeys every week.
At first, laboratory-bred monkeys were examined, after that wild-riginated
monkeys kept as breeders at this center for a long time, and then newly-imported
wild monkeys from Southeast Asia were surveyed.
One year later, this ophthalmoscopic observation was icluded in our
routine physical inspection carried out once a week.
Since then, we have been able to examine sixty monkeys a week, and have
already recorded some abnomal findings of the ocular fundus, such as
micropapilla, optic disc ectasia, myelination, tortuosity of both arterial and
venous vessels, artery-vein crossing, copper-wire artery, inosculation of the
artery, vascularization of the vein, macular degeneration and peripheral
degeneration. In addition to those, abnormal anterior ocular segments such
as cataract and persistent pupillary membrane have been recorded.
These normal and abnormal pictures will be useful for establishing
countermeasures to the diseases and clinical practices in our breeding colony,
as well as, the findings will also become very important references in the field
of ophthalmology using cynomolgus monkey as a model of man.
Page
12 A Clinical Commentar by a Cub Veterinarian: Cesarean section
At nine o'clock in the morning, our animal technicians have gone
respectively to animal rooms in charge of them.
After a while, I caught a wireless calls from Mr, N. who was working at a
room of cynomolgus monkeys. He
said, "I just found a case of rupture of bag in the room number 4." At once, I went to the room and recognized the trace of
amniotic fluid on the filth-plate of a monkey cage.
How is the monkey? I
observed her. She looked calm and
well as usual with the face asking me if there was anything wrong with me.
She had eaten up the diet given the day before.
I began to examine her. First
of all, external inspection revealed no abnormal signs except the wetting of
vulva with amiotic fluid. Then I
tried to palpate the fetus and found it showing cephalic presentation. I felt no
fetal movement, I tried to hear the cardiac sound of the fetus with a
ultra-sound apparatus, Heart-Tone. Judging
from the position of the fetal head, I pressed the probe to the supporsed
position of the heart. Rat-tat-tat,
I could hear the heart-beats through the loud-speaker, but the sound was fairly
weaker than normal one. I decided
to carry out Cesarean section for taking out the fetus more safely.
Immediately I prepared for the operation and began it.
When the abdomen was opened, the uterus of oval shape with the long axis
of about 12 cm appeared. Almost no
amniotic fluid was left in the uterus, the female baby taken out was nearly
moribund. After wiping off the
amniotic fluid in her mouth with sterilized gauze, I handed the newborn to Mr.
N. He massaged it very carefully.
I went on performing operation, taking out the placenta and removing all
other contents in the uterus. When
I almost finished suturing the uterus, I heard the babyfs cry, "Peep,
peep, peep." She has survived. About
ten minutes had passed after I took her out.
I finished the Cesarean section successfully. When we showed the baby to her mother mohkey in that
afternoon, her mother who had recovered from anesthesia stretched her hands and
hold the baby in her arms. This was
indeed that "Mother is strong."
We have about 300 delivery cases per year, in principal,natural
deliveries. In the case of
rupturing bag or bleeding on the last days of pregnancy period as well as in the
difficult deliveriy, we carry out Cesarean section.
Recently we have obtained statistical data revealing that abouzt 70 % of
the cases of breech presentation at the end of pregnancy resulted in stillbirth. To judge the timing of Cesarean operation is very important
and difficult. We are now
seaching the timing Cesarean section to save the life of the babies.
We carry out this kind of operation 20 to 30 times a year, including the
ones for some other research purposes, for example, study of the transfer of
maternal antibody (See, TPC News Vol .2 No. 3) .
By the way, both of my dear two daughters have come into this world by
Cesarean section, too.
Page
13 A Special Article: Research into biological clock by using monkeys
It is one of my great interests to know how various factors of
environments surrounding man affect the circadian rhythm of human physiological
functions and what rules exist between the environmental factors and the
rhythmicity.
There are many people who suffer from insomnia or depression.
And we often hear many complains about not illness but such troubles that
they can not live in good health or they can not concentrate themselves in works
and studies. Evidence that
biological clock may have some relations to these troubles are increasing.
I think, looking over these troubles from the view point of biological
clock is needed.
If the squirrel monkey kept under 600 Lux continuous light and 28
room temperature conditions for a long time is exposed to mild cold environment
(20)
only for 6 hours, the rectal temperature falls by 1(Fuller
er al.). In contrast to this, the
fall of rectal temperature in the monkey reared under the 12-hour-light and
12-hour-darkness cycle condition at 28 ,
is only 0.1.
This means that we should not exclusively pay attention to the ambient
temperature alone as factors responsible for the body temperature regulation.
It has been known that if humans and monkeys are kept in constant light,
their physiological functions such as rhythm of awakening and sleeping, body
temperature and hormone level deviate from their 24-hour-period.
This deviation is called a free-running rhythm.
But all of the physiological functions do not always free-run in the same
period. Each physiological function
shows its own free running rhythm, for example, the rhythm of awakening and
sleeping has a period of 25 hours, the body temperature rhythm is 24.5 hours,
etc. This phenomenon is called
internal desynchronization, and it has been known only with man (Aschoff et al.)
and monkeys (Sulzman et al.) so far.
Fuller et al, considered that the difference in the degree of fall of
their monkeys' rectal temperature has a close relation to the presence or
absence of internal desynchronization. That
is, to live under the constant light gives rise to the internal
desynchronization changing strongly the phase of circadian rhythm.
On the other hand, to live under the 12-hour-light and 12-hour-darkness
cycle condition provokes no inter al desynchronization.
It may be suggested that this situation becomes a cause of the disorder
of temperature regulation. Anyhow the development of internal de-synchronization
may have possibility to cause not only disorder of temperature regulation but
also disorders of other physiological mechanisms resulting in diseases.
In addition, it has been known that even if the internal
desynchronization is not generated, the phase relation among various rhythms of
a living body may change under constant light or different lighting cycles
(Aschoff). For example, it is said
that a patient periodic depression becomes suddenly a very early riser and this
condition continues for a little long time (Wehr et al, ) .
During the manic period, he acts vividly and livelily in a good temper.
The fact that the clinical symptoms of depression vanish by sudden
progress of the phase of awakening-sleeping rhythm suggests that there is a
close relationship between the development of depression and the phase-relations
among various internal rhythms.
It has been known that the light has a marked influence on the phase of
circadian rhythms, which affects their health state and development of the
internal desynchronization, which has been recongnized only in humans and
monkeys, therefore, the monkeys as laboratory animals play very important roll
in the study of human biological clock.
By the way, are there any other lighting conditions which occur the
internal desynchronization, except the one I mentioned above?
It has been reported that if monkeys are kept in the room where they can
switch on the light by themselves, the period of awakening-sleeping rhythm
becomes significantly longer than that under constant light (Tokura and
Aschoff). The biological clock runs
free under the self-selective-lighting. It
is very interesting to know whether or not the internal desynchronization
developes under such circumstance. At
night we turn on the light, and the actions of turning on or off the light
themselves may act as a factor which makes the period of awakening-sleeping
rhythm longer. We live under the
sunshine in daytime, and we enjoy our night life under the electric light.
Natural light and darkness may act as Zeitgeber which makes human
circadian rhythm synchronized to 24-hour-period.
The action to select artificial light for oneself at night may work as a
driving force which makes the period of his biological clock longer.
As the result of artificially lighting up at night, man has become to be
exposed to light for a long time. It
has been demonstrated that whenever the light-darkness ratio is higher or lower
than a certain level, the synchronization mechanism of living body is thrown
into confusion, exceeding the limit of adjustment. Prolongation of the lighting time resulting from the action
to select artificial ligh functions as a driving force that makes the clock run
free. On the other hand, natural
light acts as a driving force that makes the clock synchronize to 24-hour-cycle.
Therefore, I think that the baldnce between these two forces makes
biological thythms run free, detarmining the rhythms synchronized or
desynchronized. It can also be
supposed that the phase relations among circadian rhythms of various parameters
may change even when synchronization occurs.
I am expecting TPC to do experimental studies on man's biological clock
to prove these supposition to be true, using the monkeys as models of humans.
Monkey would easily be able to learn how to turn on or off the light of
the room. I think the new knowledge
of these matters will make a great contribution to the resolution of human
health and disease problems. In
Japan, as far as I know, there is no institution in which we can perform
experimental studies of human biological clock.
The significance of the study on biological clock in primates is very
large.
Once I had observed the awakening-sleeping rhythm, using three pig-tailed
monkeys. They were kept in an
individual cage and could see each other. This
experiment revieled that their circadian rhythms ran entirely free, showing the
same period. No phenomenon like
this has been observed with other animals such as birds or mice except for
humans and monkeys. That is, the
monkey 's biological clock was greatly influenced by the presence of other
monkey's, like humansf. In this respect, the role of monkeys as a model of man
is very important.
Recently it has been reported that temperature or temperature cycle gives
an influence to the biological clock controlling awakening-sleeping rhythm in
monkeys, and at the same time, back-ground luminous intensity and the
temperature also related each other to controlling the mechanism (Tokura and
Aschoff) . Previous investigators judged that the temperature had no
effect on the biological clock with regard to homeothermal animals.
However, it is not always the case with the monkey, one of the higher
homeothermal animals. How does temperature affect human biological clock?
Since the environments surrounding us are becoming more complicated, the
development of studies on biological clock is greatly expected in the field of
environmental physiology and medicine.
I believe, the studies to find out a rule between physical or social
environments and the biological clock using monkeys as laboratory animals is
very much needed.
Page-15
Homeland of the Cynomolgus Monkey : The compound of Mr.Chuck in Indonesia
Monkeys were running and jumping about vividly in cages.
They looked fairly well. The
compound of Mr. Chuck Darsono, C.V. Primates, was in a quiet suburbs of Jakarta,
Indonesia. We finished selecting
monkey in a short time, owing to kind help of Mr. Chuck.
Our next task was to observe the facilities and equipment of his
compound, which was built for both quarantine and breeding.
When we visited there, in February, 1982, 450 cynomolgus monkeys and 110
pigtail monkeys were kept. The
routine care and management taken there were as follows: daily observation of
health conditions and meclical treatment by a
veterinarian, cleaning, disinfection and feeding by seven animal
caretakers, recording of data by two office girls and microbiological
examinations by two researchers.
A building for feeding monkeys was of one story.
The floor was concreted so that it can easily be cleaned with water.
There were four quarantine rooms, two of which were under construction.
Each room was large enough to set 126 cages .
The individual cage of the quarantine room was made of iron and hung on
the wall at a height of 1.5 m from the floor.
The cages were arranged with the space of 50 cm to prevent contact
infections with monkeys in adjacent cages.
Automatic watering device was adopted.
The persons who enter the room were required to put on masks, white
clothes and rubber boots. In
addition to the four quarantine rooms, the building had other 14 rooms for
keeping animals who passed quarantine and for breeders.
Eight of them were available for keeping 50 monkeys in individual cages,
the rest 6 rooms were used for group feeding.
Mating was carried out in large cages.
Pregnant female monkeys were transfered into individual cages.
Four pig-tailed mankeys weighing 10 kg were pregnant at that time.
It is the best organized and equipped monkey compound we have ever seen,
I think.
Page-16
A Memory of a Trainee: My
experience of somatometric study at TPC for half a year
Both somatometry and osteometry used now had already been established in
early years of the 20th century. So
they may be said to be out of date. But
nowadays we can obtain various new knowledges when we analize the data obtained
by the old fashioned method with a new statistical method using an electronic
computer:that is called the multivariate analysis.
Somatometry means, in a word, a physical examination.
It sounds very easy. However,
physical examination for monkeys has a number of difficulties unlike that for
humans. I at first had to spend a lot of time to obtain accuarate
measurements of mankey's body, but at last I have become an expert of the
measurement. Then I planned the
following research subject: (1) Observation on normal body growth in colony-born
and -reared monkeys, (2) Research on the difference in body form between wild-
originated monkeys and colony-reard monkeys, (3) Study on the effect of
environmental factors upon physical growth,
To my very regret, when I finished the subject (1) with many animals of
various age classes and took the data of the subject (2) with wild-originated
animals, I had to stop and give up the work at TPC in the middle, because I had
to move to the Primate Research Institute of Kyoto University for my new
position. I, however, had already
measured more than 200 monkeys for only a half year.
I could not be too thankful to the TPCfs staffs for their kind
cooperation and help.
I have had a chance to
associate myself with not only research but also some routine works and events.
Needless to say, I think that TPC is one of the most ideal institutes for
biomedical studies in primates because of its good environments to breed and
rear laboratory primates, regarding all the aspects of the center such as
facilities, management systems and the talents.
Each staff member of the center is working very actively and vividly to
produce excellent results. I can
point out now that the driving force bringing such high activities is the warm
atmosphere, Visitors are always
welcomed in a family way, while a hi-spiritual tension is being kept at the
center. I have carried out my study
quite freely, too. Furthermore, the
activities of visiting researchers at TPC also have stimulated me very much to
further knowledge. Finally, I thank
all the people of TPC again, and hope the development of studies on nonhuman
primates as laboratory animals .
Page-17
U.S.-Japan Science Cooperatives Prog (Nonhuman Primates)
Dr. Sackettfs Exciting Lecture
at TPC - High risk, low risk monlmys
A lecture by Dr. Sackett, a world-wide authority on the study of
development in nonhuman primate behaviors ( Professor, University of Washington)
, was made at TPC on March 21 in 1984. On
that day a number of researchers and students specializing in psycology and the
science of behavior gathered from other institutes or universities to attend
with a great expectations .
The lecture began with the words of welcome and the introduction of Dr.
Sackett, by Dr. Honjo, TPCfs Director. It
was really wonderful and exciting lecture due to the witty way of his speaking
as well as to the invaluable structure and content of his story.
All the audience were greatly impressed by his passion and affection for
his study. Especially, his history
of research, in which an interest in "Life span psycology" had become
a motive for studying the development of primate 's behavior, and led him to the
study of "High risk, low risk monkey", gave every one a strong
stimulation and a lot of courage to tackle new studies.
Page-17
Characteristic behaviors of monkeys: Catching
We, animal technicians have to take good care of monkeys every day .
In this note I will
introduce you some interesting scenes I come across in our animal rooms.
The way of catching wild-originated monkeys is more or less different
from that of colony-reared monkeys. When
we catch wild-originated monkeys we use a catching net.
But we catch almost all of colony-reared monkeys by the tail without
using a catching net, because they run about in cage very wildly if we use a
catching net. Their movements
against the use of catching nets are too violent to express properly, running
around with high speed, up and down, back and forth and sometimes dashing their
heads against the wall of the cage.
A certain wild-originated monkey begins hopping as if he is warming up to
run away whenever I stand before his cage with a catching net.
He is a habitual runaway in catching time.
I have failed to catdh him several times.
Then I noticed that the ordinary way of catching is not useful for this
monkey, and found out his habit of rushing out in a certain direction when I
opened the door of his cage. I
decided to set a catching net in the place he ran through.
After that time I have never failed to catch him.
Some colony-reared monkeys are also rather peculiar in their behaviors.
For example, there is a monkey who usually jumps out the cage as soon as
I open the door. But, he can not
run but jump just like a rabbit. He
has been raised only in a small cage, he may have had no chance to learn how to
run as a monkey, I think. For
another example, there is a monkey who falls into a systemic convulsions and
lays on the floor immediately after I open the door.
According to my colleague who is in charge of this monkey, this animal
goes into spasm almost every time when he is caught.
The covulsions stop after two or three minutes.
And when I try to catch him again he has no sign of convulsions any more.
He goes into spasm only at the first time.
I am sure that he has a very sensitive heart.
In my every day works, I often meet many other monkeys showing
interesting characteristic behaviors, in addition to the three cases mentioned
above. I think that to know the
behavioral characteristics of each monkey is a duty of animal technicians to
carry out work safely and speedily.
Page-18
What I thought on my Adult's Day (20 Years of Age) Ceremony
I myself celebrated the Adult's Day (20 Years of Age) Ceremony this year.
Taro, a laboratory bred cynomolgus monkey, whose code number is
1126301001, also has become 20 years of age.
This age of twenty means to be young adult for us human, but very old for
monkeys.
It is respectable to live in a small cage for twenty years without being
given any toys, passing throughout the stages such as weaning, paired feeding
and group feeding: so to speak, the courses of kindergarten, elementary school,
junior and senior high schools. If
I were Taro, I would be crazy.
Taro's growing processes at TPC, I imagine, are as follows.
He was with his mother only until weaning, and in this breast-nursing
period he learned how to eat or play from his mother.
After the weaning, he had to live on by himself without mother's help
under the feeding condition with a peer, followed by the group feeding with
several peers.
In the group feeding, he
might have been injured and sometimes become ill.
But he could not depend on his mother even on such occasions.
After the group feeding he was separated from his peer mates into an
individual cage. Taro, since then,
has been very well in his breeding performance and become a good example to
other monkeys.
As for myself, on the other hand, I have lived under the warm protection
and help of my parents since I was born. I
might not have lived without their help and support.
I owe it to them that I am now. I
made up my mind heartily on my Adult's Day, that I would become independent and
be a good and able adult, following Taro .
Five
Big News at TPC in 1983
Page-5
Twin
babies of the cynomolgus monkey were born by Cesarean operation.
These are the second twin case we experienced here at TPC
Page-8
The cubed diet was changed in its shape from AB (solid, biscuit-type) to
AS (granule-type) .
Page-14
Early diagnostic procedure using a ultra-sound apparatus for pregnancy in
the cynomolgus monkeys has been included in our routine inspections for female
breeders.
Page-15
A
cynomolgus baby with congenital cataract was born.
Page
16 Relations
between fetal position and incidence of stillbirth were revealed in pregnant
cynomolgus monkeys .