87-1
6 February 1987
Dear Alf,
We are sending you our warmest greetings for your 77th birthday ? I’m sorry a
bit late. With the tie you gave me, I very often work in the university. This
produces the feeling as if you were looking my work, sometimes speaking to me. I
am enclosing a picture of my family, recently taken on the bay of the
in-land-sea near-by. Takako works in the hospital once or twice a week. From
April, Yoko will be a high-school student, fifteen years old. Her age reminds me
of the real career of my academic life, started in Oslo under your guidance.
We hope from the bottom of heart that the metastasis to the pelvis, very sorry
to hear, will not progress further!
Take the best care, please and relax and be peaceful. I ruminate on the
wonderful days we spent together.
With kind wishes,
Yours as ever,
Koki, Takako, Yoko
87-2
CEREBELLUM ? ORGANIZATION AND OPERATION
Symposium ? Soria Moria March 7, 1987
In honour of Alf Brodal
Supported by
Andres Jahres Fond til vitenskapens fremme
Norges almenvitenskapelige forskningsrad
Ciba-Geigy A/S
Tidsskrift for Den norske lageforening
Aftenposten
87-3
AB/G March 9, 1987
Professor Koki Kawamura, M.D.
Department of Anatomy
Okayama University Medical School
Okayama 700
JAPAN
Dear Koki,
Thank you for your last letter with congratulations to my 77 birthday, and also
for the nice picture of you, Takako and Yoko. Time passes fast, you notice it
best on the children. Before you are aware, they are grown up and have to manage
for themselves.
As to me I have had a rather good time the last months, thanks to Prednison (stereoid
preparations, the full-moon face is developing). So I have been able to do quite
a bit of work, such as writing a small piece about Moruzzi, for a forthcoming
issue of Archives italiennes, and an editorial for our Norwegian Medical
Journal. The last paper on group z in the rat is finished, and together with Per
I have started to prepare a fifth edition of my small textbook of Neuroanatomy
in Norwegian. There is enough to do. I think it is better to be occupied with
something than just to relax and take it easy.
Recently Fred and Per Andersen arranged a symposium in my honour here in Oslo.
In addition to our own people, such as Fred, Per, Espen and Ole Petter, there
were participants from Sweden, England, The Netherlands, France and the USA. I
send you a copy of the programme, and a copy of my closing remarks, that may
perhaps interest you.
I also often recall the fine days we spent together this fall, and it amuses me
that you uses the tie you got. May it bring you luck!
With my best wishes to you all,
Yours as ever,
Alf
(A. Brodal)
87-3a
Cerebellar Symposium 7/3-87
Dear friends, dear colleagues.
I am deeply moved by being honoured with a meeting this, and I will thank the
organizers, Fred and Per Oscar, and also all of you who today have contributed
to the entertainment, so to speak. For various reasons, in recent years my own
activity in the field has been very modest. Nor have I been able in any way to
keep up with what has been going on in cerebellar research in later years. It
has been very interesting, therefore, to get an orientation about this, although
admittedly much goes far beyond my comprehension.
In many ways I feel today like those persons who are invited to a meeting to
“kaste glans over begivenheten”, as we say in our language, my dictionary
translates it “to give a prestige to the meeting”. Of such persons, as you know,
nothing is expected, except their bodily presence (they are even permitted to
fall asleep during the proceedings). Nevertheless, I am tempted today to air
some personal opinions about the nervous system, which are probably well known
to many of you, and to relate some of them to personal experiences.
It is almost incredible to me that more than fifty years have passed since I was
introduced to neuroanatomy by the late professor Jan Jansen. Except for some
diversions into neurology, psychiatry and ophthalmology I have remained in
neuroanatomy. I have never regretted this. I believe it has suited my concrete
and materially oriented mind.
About 1940 nobody could foresee the wealth of new information that was to come,
due chiefly to the development of improve methods. In addition to investigations
of normal brains and malformations with the Nissl and Golgi methods at that time
we had at our disposal in anatomy a few anatomical methods that could be used
for experimental studies, such as the Weigert method and the Marchi method for
study of degenerating myelinated fibers and the mapping of retrograde cellular
changes in Nissl sections. Today we realize that our concepts of the
organization and working of the brain were extremely primitive, simple and
rigid. For example, until about 1940, the corticospinal tract was believed to
originate only from Betz cells in the motor cortex, their axons made
monosynaptic contact with motoneurons, and they were responsible for voluntary
movements. That was about all. In 1977 Phillips and Porter devoted a book of 450
pages to the subject, and still there are open questions.
Let me start with some personal experiences. My first contact with the broader
world of neurology took place at the International Congress of Neurology in
Copenhagen in 1939. Here I met many of those leading in neurology at that time.
To mention a few: Ariens Kappers and Brower from Holland, Gordon Holmes from
Great Britain, Pette from Germany, Krabbe and Wimmer from Denmark, Antoni and
Sven Ingvar from Sweden, Alajouanine and Laruelle from France. Except for
Kristian, who was also present at that congress, most of these people are
probably only names for most of you. Our own professor Monrad-Krohn took care of
introducing me to them. My reason for mentioning this meeting is the following:
After my lecture on my experimental studies of the olivocerebellar localization
both Ariens Kappers and Brower rose and expressed their appreciation of my work.
I had not expected anything of that kind, feeling very young and unexperienced
at the age of 29. It taught me a lesson which I have tried to remember when I
later got younger scientists to advise: It is important to encourage young
people when they embark on their scientific career, and not only point to faults
and weaknesses in their work.
I would like to mention another personal experience. In 1946 I went to Oxford
for a year with a Rockefeller fellowship to work under the guidance of professor
Le Gros Clark. E.D. Adrian, who was then in Cambridge, had recently demonstrated
physiologically the somatotopical pattern in the cerebellum, and I asked for an
audience. Adrian received me very cordially. I think we spent about 2 hours in
his lab. The famous neurophysiologist who had received the Nobel-prize already
in 1932, impressed me by his kind and friendly way of treating a young, immature
scientist. He was an outstanding example of what I later have experienced over
and over again: Most great neuroscientists are also very fine human beings.
Inborn personal characteristics of course contribute to this, but very likely a
lifelong occupation in any fields of the neurosciences will give the researcher
a profound awe for the wonderful complex and intricate organization of our
finest organ. Let me mention a few others: Bremer, Granit, Elizabeth Crosby,
Moruzzi, Penfield, Woolsey, Jerzy Rose, Kluver, Francis O. Schmitt, Olszewski.
Many of them are not among us any longer.
About 1950 it was still possible to know personally most leading people engaged
in the neurosciences. Since then the number of workers in our field has
increased dramatically, and new branches have evolved and expanded. At a party
in our home in 1961 John Eccles said: “The next generation will reproach us for
not having invested more in the neurosciences”. I have not met him for some
years, but I doubt whether he will subscribe to this statement today!
Within the many fields of contemporary neurosciences each largely uses its
particular methods. Main trends have been clarified in all of them. Most papers
appearing today in a steadily growing number of journals deal with details in a
particular field. It happens that findings made with different methods are not
in agreement. Provided that the studies are made with reliable methods, and that
the observations are carefully reported, there is reason to assume that the
discrepancies are only apparent. Not yet clarified details may explain them. So
we have to delve deeper into the mysteries. That is, we have to look for ever
more intricate details. There seems to be no end to this procedure.
If we are searching for main principles in the organization of the nervous
system, integration of observations from various fields is needed. This requires
the collaboration between specialists in different disciplines. There is
nowadays a growing proportion of such so-called “interdisciplinary” studies. If
this collaboration is to be fruitful, however, each of the participants must
have a general knowledge of methods and principles of the other fields involved.
As the wealth of data increases, in the future integration will become
incessantly more difficult.
In the study of any organ knowledge of its function is essential. It is
difficult, if at all possible, to imagine a function that is not mediated by ?
and dependent on ? a structural basis. This holds true from the macroscopical
down to the so-called utlrastructural level. This means that for a full
understanding of any functional phenomenon we will have to know also its
morphological substrate, that is its anatomy. In addition, anatomy serves as a
common reference frame for observations in all other fields.
In modern neuroanatomical research two main fields are noteworthy. One concerns
the large amount of new information of the structure of synapses and their
arrangements. I will restrict myself to the other feature, the detection of a
wealth of new, hitherto unknown, fiber connections. Details in the pattern of
connections go far beyond what was formerly known. Some of the newly discovered
connections are not massive, but it is difficult to imagine that they have no
function. If so, they would probably have fallen the victim of atrophy.
Among the variety of interconnections certain arrangements appear to be common
to probably all parts of the C.N.S. There are parallel, monosynaptic ? or
indirect, polysynaptic ? interconnections between them. Reciprocal, feed back
connections are the rule. Most connections are to a certain extent bilateral.
Commissural connections occur at all levels of the nervous system. Internuncials
and local circuits appear to exist everywhere. All axons give off collaterals.
Localization between regions is not, as was formerly often believed, sharp, but
overlapping and arranged in multiple foci in a mosaic pattern. We find examples
of these arrangement in the cerebellum as we heard today. Finally, let us not
forget that the plasticity of the nervous system, which seems to be a
prerequisite for any kind of learning, is also valid for the cerebellum.
If I were to give a general view of the organization of the central nervous
system based on its structure, I may quote myself from a lecture entitled “The
wiring pattern of the brain”, delivered at a symposium in honour of Francis O.
Schmitt in 1973: “We may consider the nervous system as being made up of a
multitude of small units, each with its particular morphological (and presumably
functional) features. These units collaborate by way of an immensely rich,
complicated and differentiated network of connections, which are very precisely
and specifically organized. The anatomical possibilities for (more or less
direct) cooperations between various parts of the brain must be almost
unlimited.” In essence this means that by way of its multifarious connections
under given circumstances any small part of the brain must be able to influence
practically every “function” or kind of behaviour.
The older I have grown, the more I have been fascinated by the extremely close
relations between somatic, visceral and mental functions. In accord with the
view I have just mentioned, recent research has brought forward more and more
evidence for the close cooperation between psychic and bodily functions. The
most clearcut example of a morphological basis for concordant psychosomatic
action is perhaps given by cells of the reticular formation. Dichotomizing axons
of many of its cells are common, one branch passing to the spinal cord, the
other to the thalamus. In addition they give off collaterals to cranial nerve
nuclei and other cell groups in the brain stem. It is indeed interesting that
even the immune apparatus has been shown to be modulated by the nervous system.
A new field is developing: Psycho-neuro-immunology.
As to the cerebellum, it has been known for a long time that it is involved in
the control of motor functions, including oculomotor activity, and in vegetative
processes. The demonstration that the cerebellum has direct reciprocal
connections with the hypothalamus contributes to explain its influence on
emotional behaviour and reactions. Although the various spheres of cerebellar
control are to some extent the tasks of different parts of the cerebellum, the
machinery they employ appears to be essentially identical. In recent years the
idea of the cerebellum as a “learning machine” has been in focus. If so, it
might be imagined to be of importance for all kinds of learning.
In the Behavioral Sciences in 1986, Leiner, Leiner and Dow from Oregon have
published an article entitled “Does the Cerebellum Contribute to Mental Skills?”
(Behavioral Neuro-Sciences, vol.100, 443-454, 1986) and discuss this problem.
Neurosurgeons have noted that stereotactic lesions of the most lateral parts of
the cerebellar hemisphere in man do not give rise to detectable motor
disturbances, as one might have expected. The authors point to the fact that in
man the cerebellar hemispheres and particularly the lateral part of the dentate
nucleus are more developed than even in anthropoid apes. This lateral part is
histologically, embryologically and histochemically different from the medial
part. Several anatomical and physiological studies in monkeys and apes indicate
that fibers from the dentate nucleus supply divisions of the thalamus that
project to the frontal association cortex. Scanty evidence from human studies
seems to be in agreement. The authors studied a patient who had a lesion of the
lateral part of the dentate and found that there was a defect in his capacity to
respond to anticipatory clues, in addition to the defects in performing motor
acts correctly. As they phrase it: “the ideational manipulations that precede
planned behaviour were suffering.” The findings made concern only effects on the
planning of motor functions. To discover whether the cerebellum is of importance
for the learning and performance of purely mental skills, will be a difficult
task, particularly since the studies will have to be made on human beings. It is
not inconceivable, however, that by using appropriate psychological tests and
tomographic procedures, demonstrating areal differences in blood flow and
metabolism some information could be obtained.
We must admit that we still know rather little about the projections from the
parietal cortex via the pons. Could the heavy projections to the cerebellum be
an indication that they are not primarily or only of importance for the motor
functions of the cerebellum?
I must confess that to me Leiner, Leiner and Dow’s hypothesis is attractive. The
cerebellum and the cerebrum may both be engaged in all our activities. Perhaps
the old German terms, Kleinhirn and Grosshirn (adapted in Norwegian as
lillehjernen og storhjernen) are justified in a wider sense than with reference
to their relative sizes only? To prove an answer to this field be the task of
the young generation of neuroscientists. Let me add finally that, regardless of
how much we will be toiling with the central nervous system, I believe we shall
never be able to solve the mind-body-problem.
87-4
KK/kf
Professor emeritus Alf Brodal
Anatomical Institute
University of Oslo
Karl Johans gate 47
Oslo 1, Norway
24 March 1987
Dear Alf,
Thank you for your letter of 9th of March and a copy of your closing remarks of
the Cerebellum symposium in honour of yourself. I am very grateful and feel very
happy to have got such a kind privilege from you to read and think seriously
about the academic life and future prospect of Neurology-Psychiatry-Immunology
in which I am deeply interested in and through which I wish to walk if or when
circumstances allow me.
Recently, I have started to study, possibly in connection with CNS, Immunology
and genetics. To say the truth, this is rather exaggeration, modestly speaking
it is the level of post-graduate student.
We are indeed glad to hear that you have been doing in recent months such nice
scientific works as mentioned in your letter, in spite of your less favourable
bodily condition. Three of us respect, admire and encourage you.
A picture, enclosed, of myself with the tie may amuse you. Other two pictures
were taken several weeks ago while we were traveling in Osaka.
With best wishes and warmest greetings from Takako, Yoko and myself.
Yours as ever,
(Koki Kawamura)
Encl. 3 pictures
87-5
April 20, 1987
Dear Koki,
Thank you for your last letter and the three enclosed nice photos.
It is interesting that you are planning to work in the direction of neuro
immunological problems, but I am afraid that it will be rather laborious and
time-consuming to get sufficient insight in there without previous knowledge.
But certainly there will be important and interesting things to find in this
field.
As to myself I am still almost free from pains on “Prednisone” treatment, but
unfortunately it is not possible to work in the garden where we now have
krokuses and other flowers coming up. If I do, the pains reappear. So I am
confined to mental work, and try to be busy that way. All is well with the
children and their families, they have all been up in the mountains during
Easter.
With kind wishes to all three of you
yours as ever,
Alf
87-6
13 / Aug ’87
Dear Alf,
I am sorry I have not written for some time. We are fine. We do hope all’s well
with you, keeping reduced activities as you told me. I am going to IBRO meeting
in Budapest and I see Per there and other Oslo people.
Do you remember last time at your home that you gave me suggestion to rewrite a
fastigial paper ? visual imputes ?.
It looks a fairly long time because if some reasons ? main one is a long
distance to each other among authors for doing discussion.
Now the manuscript is about the final stage for submitting. I am sending the new
version of the manuscript under separate cover. I would be very grateful if you
could take your time for reading this and give me comments (and also linguistic
correction). If you feel it’s better to be read by other people, e.g. Per, I’m
also grateful. I’ll be back from Budapest and regret that I cannot directly
visit you this time.
With kind regards,
Yours as ever,
Koki
87-7
Aug.20, 1987
Dear Koki,
Thank you for your letter of Aug.13. I am happy to hear that you are all well. I
have read your paper with interest, but unfortunately I do not feel capable to
review it properly. I may ask Per when he returns from Budapest.
As to myself I have been almost free from back pains the last months, provided I
take care not to bend or twist my back. Some weeks ago, however, I started to
have angina pectoris, rather moderate, however, but not pleasant. I am using
Nitroglycerin when it gets troublesome. But equally disturbing is a feeling of
dizziness and tiredness, so little sensible work has been possible the last
time. My heart doctors’ treatment has resulted in a marked reduction of my blood
pressure, some times was as low as 100/70! This may be good for the heart,
perhaps, but I have a suspicion that it is not enough for the brain in my age.
Time will show.
The summer has not been good this year, too much rain. I have managed however,
to be some days on our cottage in Tuddal with Anne Brit and Per and their boys.
I send my warmest greetings to all of you,
yours as ever,
Alf
87-8
25 / Sept ’87
Dear Alf,
Thank you for your letter of Aug.20th, and sorry to hear that you are in general
not happy in health. We sincerely hope that you can have much time when the
pains in the heart and back are free. Meeting Per in Budapest was fine, and he
was so kind to send me back the fastigial manuscript with comments. I hope we
can manage to revise it in two weeks from now; I have been very busy in teaching
duties up to now. Exp. Brain Res. has recently accepted our paper: grafted
granule and Purkinje cells can migrate into the mature cerebellum of normal
adult rats. Also, a short paper of “Identification of T lymphocyte
subpopulations associated with rejection of intraparenchymal allograft in the
mouse brain” has just been submitted to Neuroscience Letters. Thus our works in
the new field are progressing, although slowly.
At this very moment, Keiko University at Tokyo, the best private Univ. in Japan
offered me a prof-position, where I can continue and extend my present research
immediately using neurobiological techniques including gene manipulation. Having
discussed problems with Takako and Yoko, I finally accepted to move from
Okayama, where we spent only two years and so, to Tokyo next April. Mothers of
Takako and me, both are widows living around Tokyo area were very glad to hear
our decision, although I feel very sorry for Yoko (school-problem) and for
Okayama University. Yoko, however, is happy hoping the possibility that she can
choose a university or college in Tokyo (although) two years ahead from now. I
am sorry that I talked too much concerning myself.
We are glad to hear that you enjoyed the cottage-life in Tuddal this summer with
your children and grand-children. I wish I can visit you again in not-so long
future.
With kind regards,
Yours,
Koki
87-9
AB/G November 6, 1987
Professor Koki Kawamura, M.D.
Department of Anatomy
Okayama University Medical School
Okayama 700
JAPAN
Dear Koki,
Thank you for your kind letter of Sept.25th.
I am indeed late in replying to it and sorry to tell you that my situation has
deteriorated considerably since then. Last fortnight I have been in Hospital (Barum
Sykehus) where they have tried to combat the pain that is rather heavy and
discomforting. The use of morphine makes me dizzy and confused, and also gives
trouble with the bowels and bladder. Muscular force is rapidly declining.
I may congratulate you with the position in Tokyo, and hope you will find that
it suits you. You are indeed working with interesting problems. To me they seem
to be extremely intricate and difficult.
I will hope that both Takako, Yoko and your mothers will find the situation in
Tokyo satisfactory. The children ask me to convey their best regards to Takako,
Yoko and you.
This letter (that is written by Per after my dictation) also brings my warmest
regards and thanks for many years of fine collaboration.
Yours as ever,
Alf
(A. Brodal)
87-10
Dear Alf,
Thank you for your kind letter of Nov.6. Putting the tie you gave me last
autumn, I send you a passage from Goethe.
Halte nur die Zeit
Du bist so shon!
Yours as ever,
Koki
17 / Nov. ’87
87-11
11 / Nov. ’87
Dear Per,
Thank you for your father’s letter, written by you after his dictation.
Please forgive me this short, quick letter.
I would ask you to pass this card, enclosed, to your great father, dear Alf.
Since I don’t have the address of Barum Sykehus.
Yours,
Koki
87-12
Dear Alf,
On your birthday, we send you our warmest greetings. Under separate cover, I am
sending you a copy of the 1st transplant paper upon which you gave me comments
at your home. With cordial thanks.
Yours as ever,
Koki
20 / Jan. ’88