Table Of ContentAdvances in the Biosciences
Editor: G. Raspe
Associate Editor: S. Bernhard
Editorial Board:
E.Gerhards
H. Gibian
M.Kramer
K.-H.Kolb
G.Laudahn
F. Neumann
E. Schröder
R.Wiechert
The Schering Symposia and Workshop Conferences
are conducted and sponsored by
Schering AG, 1 Berlin 65, Müllerstraße 170
Advances in the Biosciences 2
Schering Symposium on Biodynamicsand
Mechanism of Action of Steroid Hormones
Berlin, March 14 to 16,1968
Editor: Gerhard Raspe
Pergamon Press · Vieweg
Oxford · London · Edinburgh · New York
Toronto · Sydney · Paris · Braunschweig
Editorial Assistance: Werner Schröder
1969
All rights reserved
Copyright © 1969 by Friedr. Vieweg + Sohn GmbH,
Verlag, Braunschweig
Library of Congress Catalog Card No. 74-76593
Set by Friedr. Vieweg + Sohn GmbH, Braunschweig
Printed by E. Hunold, Braunschweig
Bookbinder: W. Lange lüddecke, Braunschweig
Cover design: Herbert W. Kapitzki, Frankfurt
Printed in Germany
08 006942 8 Pergamon Press
7681 Vieweg
Advances in the Biosciences 2
Opening of the Symposium
G. Raspe
Schering AG, 1 Berlin 65, Müllerstraße 170-172, Germany
Good Morning, Ladies and Gentlemen:
It is a particular pleasure for me to welcome you all here at our laboratories. We
are very grateful to you that you have accepted our invitation to participate in this
Symposium. On behalf of the auditorium. I may express our sincere thanks to the
lecturers and to the moderators of the Panel Discussion on Saturday.
As many of you know, this is the second time we are sponsoring a Symposium of
this size on hormones. The first Symposium took place in May, 1967, and was
linked with the inauguration of this building and with Professor Junkmann's 70th
birthday. We, Dr. Kramer, Dr. Gibian, Dr. Gerhards, and myself with many others
of our group, have considered very carefully if we should organize a second Sym-
posium. Based on Dr. Gerhards's concept of the topics to be dealt with and the
readiness of the speakers we have decided to do so. I would like to invite everybody
in the audience to advise us if and how we should continue to plan and to sponsor
our meetings. We shall appreciate any suggestion.
The consideration which I have mentioned has led to some delay in the printing of
the Proceedings of the First Meeting. We can assure you, however, that the Pro-
ceedings of both Symposiums will be in your hands within a reasonable time.
Now why did we choose this winterly season for the meeting? As some of you
have already realized, we have chosen the week after the Symposium of the
"Deutsche Endokrinologische Gesellschaft". This may in future enable scientists
from other countries to participate in both meetings and to spend the days between
in this country.
The topics of this symposium on "Biodynamics and Mechanism of Action of
Steroid Hormones" involve manifold aspects which have been actively studied by
a large number of groups. Let me put the basic questions which were included in
these aspects:
1. Where and how are the steroid hormones produced in the body, what is their
chemical nature and their metabolic fate?
1 Bioscience 2
2 G. Raspe
2. How do the systems which govern production, release, distribution, metabolism
and excretion cooperate during different physiological and pathophysiological
states?
3. What effects are involved in the molecular mechanism of action?
As to the first question which is, of course, strongly linked with the two others, a
vast amount of facts has been accumulated since the "thirties". Almost 40 years
ago, the first metabolites, respectively precursors of steroid hormones were isolated
by Doisy (estrone, 1929), and Butenandt (dehydroepiandrosterone, 1932), not
knowing that they were not the true hormones. The first studies aiming at the iso-
lation of metabolites of known hormones were published by Venning and Brown
(preganediol, 1937), and Steinach and Kun (estrogens, 1937). The inspiring studies
by Zondeck and Bühler should also be remembered.
The introduction of new methods for the determination of structures like UV
and IR spectrography, NMR, mass spectrography, x-ray defraction analyses etc.
between 1946 and the fifties as well as the development of specific color reactions,
paper and thin layer chromatography, have led to more sophisticated work on
biosynthesis and metabolism of steroid hormones.
Up to now, a large number of steroid derivatives were isolated from biological
sources, amongst these 200 from urine. The development and use of new physical
and chemical methods will be decisive for further progress in this field. We are,
therefore, very happy to have Professor Spiteller lecture on methodological subjects.
More sensitive and more specific analtical methods including the use of labelled
steroids with high specific activity had to be available to study biodynamics of
steroid hormones. The first and most important contributions were made by
Jensen, Lipsett, Migeon, Peterson, Samuels, Tait, and their co-workers between
1956 and the early sixties. Compartmental analyses using mathematical models
need carefully selected methods. Even realizing the difficulties in its performance,
there is obviously no reasonable substitute to gain insight into the counterplay of
tissues involved in biosynthesis, distribution, interaction with target tissues and
ultimate disposal of steroid hormones. The papers by Professor Baulieu, Professor
Breuer, Professor Lipsett, Professor Schriefers, Professor Vermeulen, and Professor
Vestergaard will deal with related problems.
Many investigators working in the field of steroid hormones have dedicated their
efforts to problems related to the mechanism of action. Also some of the work on
metabolism was obviously stimulated by the expectation that metabolic steps may
include processes which could lead to the understanding of the mechanism of
action. Many hypotheses have been deviced by Dirscherl, Dorfman, Green, Hamilton,
Hecker, Karlsson, Talalay, Tomkins, Villee and others; some of them have already
been modified or excluded. The following figures give examples for the extent of
hypothetical thinking:
Opening of the Symposium 3
The work on the mechanism of action of steroid hormones has been favoured by
the independent development of the molecular mechanism of protein synthesis.
The influence of different steroids on RNA synthesis seems to be solid ground for
further progress.
The findings of Edelmann, Gorski, Jensen and Toft and their co-workers lead to
the consideration of hormone binding to specific proteins as an initial step of
steroid hormone action. Aspects of target organs specificity are also included in
this concept.
Although many beautiful schedules have been drawn there is still a gerat number
of questions as to the last steps of the action of these hormones on the molecular
level. The binding to specific repressors has not exceeded the hypothetical stage.
The twofold action of androgens (morphogenetic and activational) as well as the
mechanism of tumor induction by hormones leads to additional considerations.
We are delighted to have Professor Huseby, Dr. Jungblut, Professor Samuels,
Dr. Sekeris, Professor Wacker and Professor Williams-Ashman lecture on the subject
of mechanism.
This institute has to dedicate its activity to achieve therapeutic progress. This in-
cludes, of course, gaining basic knowledge on the understanding of physiological
systems. Having this objective, we are realizing that only a small part of the results
which were obtained by working on the metabolism of steroid hormones as well
on their biodynamics and on their mechanism of action could be incorporated into
methods for treatment and diagnosis of endocrine and other diseases. Because of
this, we have inserted into the program the Panel Discussion which is supposed to
take place on Saturday and should lead to the putting of questions by the Panel
and the audience.
I have now the very great pleasure of introducing to the audience the winners of
the Schoeller-Junkmann-Prize of 1968. The first prize has been awarded to Dr.
Elger, Dr. Neumann, and Dr. Steinbeck of this laboratory for their studies entitled:
"Untersuchungen zur gestörten und normalen Sexualdifferenzierung" (Studies on
the normal and pathological sexual differentiation).
The second prize has been awarded to Dr. Fraschini, Dr. Motta, and Dr. Martini
from the Department of Pharmacology of the University of Milan for their work
on "Neural control of anterior pituitary functions".
The third prize has been awarded to Dr. Breustedt from the Institute of Pathology
of the University of Hamburg for his work entitled "Zur immunhistologischen
ACTH-Lokalisation in der Rattenhypophyse und in einem experimentellen Hypo-
physentumor (MtTF )". (On the immuno-histological detection of ACTH in the
4
rat pituitary and in an induced tumor of the pituitary).
4 G. Raspe
We wish to congratulate the winners, and we are happy that they participate in
this Symposium. I think they can easily be detected in the audience.
My last and very pleasant task is to introduce our first speaker, Dr. Elwood V.
Jensen who has agreed to open the Symposium with his lecture on the Science of
Science.
Advances in the Biosciences 2
The Science of Science
E.V.Jensen
The University of Chicago, The Ben May Laboratory for Cancer Research,
950 East 59th Street, Chicago, Illinois 60637, USA
In Chicago, one peaceful morning in February, our deliberations concerning
estrogen receptors were interrupted by the ringing of the telephone. The caller,
Dr. Martin Friedrichs, announced in all honesty he was trying to find a philosopher.
Now this indeed was a novel situation. In the olden days, you will recall, the philo-
sopher, lantern in hand, went about seeking an honest man; here was an honest
man searching for a philosopher.
"You have come to the right place," I told him, looking around for my Stein der
Weisen. "I am a Doctor of Philosophy. What can I do for you ? "
"How would you like to go to Berlin ? " he asked, the name Berlin bringing to mind
such great philosophers as Hegel, Fichte, John le Carra and Len Deighton. "Fine,"
I said. "When do we leave ? "
"Whenever you like," he replied, assuming a manner similar to that with which
Mephistopheles beguiled Dr. Faustus. "But, first we must make a small bargain.
In Berlin some scientists will assemble to discuss the biodynamics of hormones. All
you have to do is give them a little philosophical lecture on the science of science."
At first this appeared harmless. We all believe that science is a good thing; therefore
the science of science should be even better, by one order of magnitude. But on
further consideration, I began to have misgivings, especially when Dr. Friedrichs
revealed the names of some of those who would be in attendance. These were all distin-
guished investigators whose business was science. How could anyone, except perhaps
Rudi Dutschke, presume to tell such experts how to run their business ? Discretion
suggested that one should heed the admonition of Lyndon Johnson and not travel
outside the western hemisphere. But thoughts of the Kurfürstendamm, Charlotten-
burg and „Weisse mit Schuss" proved stronger than the voice of reason. So here I
am in my assigned capacity to discuss with you „Die Wissenschaft der Wissenschaft."
Sometimes I feel that a more appropriate title might be "Funeral in Berlin."
Science, Research and Philosophy
Before undertaking any philosophical appraisal of science, one might consider what
we mean by science, research and philosophy. Let us define science (from scire,
6 E. V. Jensen
"to know") as systematized knowledge formulated with regard to the discovery
of general truths and the operation of general laws, research as critical inquiry
seeking new facts or principles which extend or modify science and philosophy
(literally "love of wisdom") as a rational study of the basic principles of a particular
branch of knowledge. According to Ingle [1] the general aims of science are to
understand natural phenomena and to predict and control them. Progress in science
depends on research. In our discussion today, which I hope will be rational and
thereby philosophical, I would like to consider with you some of the factors which
influence the nature and significance of research in the biological sciences.
The Template for Research
The research accomplishments of any scientist or group of scientists might be judged
by their productivity or total output, by their efficiency or output in relation to the
effort and expense invested and by the originality and significance of their disco-
veries in opening new areas of knowledge. Success in research is subject to influence
by a variety of factors, some which originate with the investigator himself and thus
may be called intrinsic, and others which depend on his environment and which we
shall term extrinsic. Intrinsic factors include the scientist's motivation, his back-
ground and training, his choice of a problem, his approach to the problem and his
adherence to sound research principles. Some extrinsic considerations are the facili-
ties and equipment at the scientist's disposal, the source and nature of his financial
support, his situation in regard to security and professional advancement, the
research organization in which he works, the current state of knowledge in his
particular field and, finally, that unpredictable element of chance, or as some would
call it, luck.
The foregoing factors are not mutually independent; one may exert considerable
influence on another, and extrinsic factors may modify intrinsic factors. Their rela-
tive importance varies from individual to individual, and the overall pattern is unique
for each investigator or research team. Still I find it interesting to examine these
factors and their interplay to see if we can formulate any impressions or generaliza-
tions to use as guides to more productive research in the future.
Intrinsic factors
What motivates a person to become a research scientist ? The answer, of course,
differs considerably from one individual to another. But it is safe to say that, for
most scientists, the desire for great wealth or public acclaim is not a primary consi-
deration. Such aspirations can be better fulfilled in other fields, such as entertain-
ment where a third rate guitar player may receive the same remuneration for a
thirty minute television program that a scientist receives for a month in the laboratory.
The Science of Science 7
No doubt most scientists today do expect a somewhat better situation than they did
in 1669 (Fig. 1); in fact a few might even be tempted by the palace and crown
jewels in Tehran. It is also true that most scientists appreciate recognition of their
accomplishments by their scientific peers. This desire may vary in intensity from
the driving ambition so candidly and lucidly portrayed in Watson's book "The
Double Helix" [2], also known as "What Makes Jimmy Run", to that of
/. Willard Gibbs, whose contemporaries, even on the Yale campus, were unaware
that he was laying much of the foundation of thermodynamics and modern physical
chemistry.
Fig. 1
For most scientists the desire for approbation probably lies somewhere between
these extremes, with another important source of motivation being simply that
research is fun. The intellectual challenge of probing nature's secrets, the excitement
of doing something no one has done before — at least until the competitor's paper
appears — and the satisfaction of having contributed in some measure to mankind's
accumulated knowledge all provide bait to lure the investigator to the bench. For
research to flourish, conditions must be such that these satisfactions can be realized.
In regard to the proper background and training for research, who can say what is
best ? The biological sciences provide a unique scientific frontier where major
discoveries can be made by investigators trained in a variety of disciplines. You
all are familiar with the numerous examples of important advances in biology and
medicine contributed by chemists, biochemists and physicists, who have brought
fresh approaches and new methodology to bear on the complex systems of the
living organism. Less important than the actual training discipline is one's capacity
for astute observation and logical deduction.
