Ciba Foundation Symposium - Cell Differentiation

296 Pages·1967·13.331 MB·English

CELL DIFFERENTIATION
CELL DIFFERENTIATION
A Ciba Foundation Symposium
Edited by
A. V. S. DE REUCK
and
JULIE KNIGHT
J. & A. CHURCHILL LTD.
104 GLOUCESTER PLACE
LONDON, W.1 I967
First published 1967
Containing 43 illustrations
Standard Book Number 7000 1338 5
Library Congress Catalog Card 67-26433
of No.
ALL RIGHTS RESERVED
This book is protected under the Berne Convention. It may not be reproduced by any
means, in whole or in part, without permission. Application with regard to reproduction
should be addressed to the Publishers.
Printed in Great Britain
Contents
A. Haddow Chairman’s opening remarks I
M. Abercrombie General review of the nature of differentiation
3
Discussion Abercrombie, Feldman, Lash, Paul, Waddington, Weiss 12
M. D. Rosenberg Single cell properties-membrane development 18
Discussion Ambrose, Bell, feldman, Grobstein, Paul, Rosenberg,
Sherbet, Waddington, Weiss 35
J. Brachet Biochemical changes during fertilization and early
development
39
DiscussioR Bell, Brachet, Engelhordt, Gurdon, Monroy, Weiss 61
J, B. Gurdon Nuclear transplantation and cell differentiation 65
Discussion Bell, Brachet, Feldman, Gurdon, Monroy, Paul, Waddington,
Weiss, Yamada 74
M. Feldman Studies on the feedback regulation of haemopoiesis 79
1. Bleiberg
Discussion Feldman, Grobstein, Lash, Paul, Rosenberg, Waddingtan,
Wolf 90
General Discussion Ambrose, Bell, Curtis, Feldman, Grobstein, Lash, Monroy,
Paul, Rosenberg, Waddington, Weiss 93
E. J. Ambrose Possible mechanisms of the transfer of information
between small groups of cells 101
Discussion Abercrombie, Ambrose, Grobstein, Lash, Monroy, Wadding-
ton, Weiss, Wolf I10
T. Yamada Cellular synthetic activities in induction of tissue trans-
formation I
I6
Discussion Bell, Feldman, Grobstein, Gurdon, Paul, Weiss, Yamada I 27
C. Grobstein The problem of the chemical nature of embryonic
inducers 131
Discussion Bell, Curtis, Feldman, Grobstein, Kirby, Lash, Waddington,
Wolf I36
General Discussion Bell, Kirby, Lash, Paul, Waddington, Weiss, Wolf
I39
G. P. Georgiev Some aspects of the regulation of gene expression in the
animal cell 148
Discussion Bell, Birnstiel, Georgiev, Gurdon, Kirby, Monroy, Paul I 58
Bell Control of synthetic activity during development I63
E.
F. R. MacKintosh
Discussion Bell, Birnstiel, Brachet, Feldrnan, Gurdon, Kirby, Monroy,
Paul I74
M. Birnstiel Some experiments relating to the homogeneity and
arrangement of the ribosomal RNA genes of Xenopus
laevis I78
Discussion Bell, Birnstiel. Curtis, Gurdon, Kirby, Paul, Sherbet,
Waddington, Yarnado I92
J. Paul Masking of genes in cytodifferentiation and carcino-
genesis I96
Discussion Arnbrose, Bell, Birnstiel, Brachet, Feldrnan. Georgiev,
Gurdon, Kirby, Monroy, Paul, Sherbet, Vendrely, Waddington,
Weiss, Whisson, Yarnada 202
Et. Wolff Factors of growth and maintenance of tumours as
Em. Wolff organized structures in vitro 208
Discussion Abercrornbie, Arnbrose, Curtis, Feldrnan, Paul, Vendrely,
Waddington, Weiss, WoIK Mme. Wolf 215
M. E. Whlsson The interaction of tumour and embryonic tissue in vivo 219
Discussion Bell, Gurdon, Weiss, Whisson, Wolff 23 I
General Discussion Ambrose, Bell, Brochet, Curtis, Feldrnan, Grobstein, Gurdon,
Kirby, lash, Paul, Monroy, Waddington, Weiss, Whisson,
Yamada 233
A. Haddow Chairman’s closing remarks 246
Author index 249
Subject index 2K)
Membership
Symposium on Cell Differentiation, held 3Ist January-2nd February, 1967
Sir Alexander Haddow Chester Beatty Research Institute, London
(Chairman)
E. J. Ambrose Chester Beatty Research Institute, London
E. Bell Dept. of Biology, Massachusetts Institute of Technology,
Cambridge, Massachusetts
M. L. Birnstiel Institute of Animal Genetics, Edinburgh
J. Brachet Facult6 des Sciences, Universitb Libre de Bruxelles,
Belgium
A. S. G. Curtis Dept. of Zoology, University College, London
W. A. Engelhardt Institute of Molecular Biology, Academy of Sciences of
the USSR, Moscow
M. Feldman Weizmann Institute of Science, Rehovoth, Israel
G. P. Georgiev Institute of Molecular Biology, Academy of Sciences of
the USSR, Moscow
C. Grobstein Dept. of Biology, University of California, San Diego,
California
J. 8. Gurdon Dept. of Zoology, Oxford
K. S. Kirby Chester Beatty Research Institute, Pollards Wood
Research Station, Chalfont St. Giles
J. W. Lash Dept. of Anatomy, University of Pennsylvania, Phil-
adelphia, Pennsylvania
A. Monroy lstituto di Anatomia Comparata, Universita di Palermo,
Sicily
1. Paul Cancer Research Department, Royal Beatson Memorial
Hospital, Glasgow
M. D. Rosenberg College of Biological Sciences, University of Minnesota,
St. Paul, Minnesota
G. V. Sherbet Chester Beatty Research Institute, Pollards Wood
Research Station, Chalfont St. Giles
Vendrely lnstitut de Recherches Scientifiques sur le Cancer,
R.
Villejuif (Seine), France
C. H. Waddington Institute of Animal Genetics, Edinburgh
P. A. Welts Rockefeller University, New York
M. E. Whlsson Chester Beatty Research Institute, London
Et. Wolff Laboratoire d'Embryologie ExF " 6rimentale, Colibge de
Em. Wolff France, Nogent-sur-Marne, rance
T. Yamada Biology Division, Oak Ridge National Laboratory, Oak
Ridge, Tennessee
The Ciba Foundation
The Ciba Foundation was opened in to promote
1949
international co-operation in medical and chemical re-
search among scientists from all parts of the world. Its
house at Portland Place, London, has become a meeting
41
place well to workers in many fields of science. Every
known
year the Foundation organizes from six to ten three-day symposia
and three or four one-day study groups, all ofwhich are published
in book form. Many other informal meetings also take place in
the house, organized either by the Foundation or by other
scientific groups needing a place to meet. addition, bedrooms
In
are available for visiting scientists, whether or not they are
attending a meeting in the building.
The Ciba Foundation owes its existence to the generosity of
CIBA Ltd, Bade, who, realizing the disruption of scientific
communication caused by the war and by problems of distance,
decided to set up a phdanthropic institution whose aim would
be to overcome such barriers. London was chosen as its site for
reasons dictated by the special advantages of English charitable
trust law, well as those of language and geography.
as
The Foundation’s many activities are controlled by a small
group of distinguished trustees. Within the general framework
of biological science, interpreted in its broadest sense, these
activities are well summed up by the Ciba Foundation’s motto,
Consocient Gentes-let the nations come together.
Preface
WEo we this meeting to the initiative of Sir Alexander Haddow
and Professor C. Waddington, who suggested that one of the
H.
Ciba Foundation’s small international symposia should be con-
cerned with Cell Differentiation. The Foundation was more than
happy to agree with this proposal, and it is a pleasure now to
express heartfelt thanks, not only to Sir Alexander and
our
Professor Waddington, but also to Professor E. J. Ambrose and
Professor Michael Feldman, for the care and time that each devoted
to helping with the organization of the programme and to
suggesting the participants.
The Foundation, the members of the symposium and also the
readers of this book have further reason to be gratefbl to Sir
Alexander Haddow, as chairman, for his skilful and gentle
guidance of the discussions.
If more questions are raised than answered in this symposium,
we feel that this may in itself be a fruitful contribution to progress
in ths vital field.
CELL DIFFERENTIATION
Edited by A. V. S. DE REUCK and JULIE KNIGHT
Copyright 0 1967 Ciba Foundation
CHAIRMAN'S OPENING REMARKS
SIRA LEXANDHERA DDOW
ALLa ssembled here are constantly preoccupied by what is still the great
mystery of differentiation. In my case, and for several others here, there is
a special applicability to the problem ofcancer, where it is basic. In my own
laboratory we have not been able to contribute directly to fundamental
studies of differentiation until more recently, but I have been struck by the
approach of Dr. R. J. Goldacre, over the past few years, in his construction
of ingenious electronic models involving the passage of signals from one
unit to another in symmetrical ways and eventually demonstrating the
emergence of polarities and new kinds of symmetry and asymmetry.
Models such as these may seem remote from cell differentiation, but they
have caused us to think a great deal about interactions between cells and their
relationship to the development of differentiated patterns. And of course
from the beginning there has been clearly recognized in the cancer cell the
presence of stages of de-differentiation. The relationship is not entirely
simple, but perhaps near-perfect. We recognized structural de-differentia-
tion; still later functional de-differentiation; and, most recently and in much
greater chemical detail, biochemical loss and deletion. All this must ulti-
mately involve studies of energy relations, and it may be justifiable to
regard what we call the normal state and the malignant variant as consti-
tuting two separate energy levels, the transition from one to the other being
facile and the reverse extremely difficult or thus far impossible.
When the German schools of pathology first examined the microscopy
of the cancer cell they were immediately struck by the analogy with the
embryonic state. Some have recently felt that in spite of the work of the
intervening 14oycars,w e have overlooked this, and that now is the moment
for further study of the analogy. There is a good deal of old biochemical '
work suggesting that in the embryonic cell many enzymic systems that are
found later are ostensibly absent, but we realize that the precursors are
present, and the old suggestion was of an orderly emergence of these
regulatory systems, slowly bringing cells into various kinds of differentia-
tion and relenting their speed of growth. In the last few years we have had
much evidence to suggest that the cancer cell is similarly defective but
permanently so, and it is possible that hcrc is the key difference.
CELL D1FF.-I I
2 ALEXANDEK HADDOW
SIR
Furthermore, for many years we and others have compared the special
biochemical properties of the cancer cell with what we called the corres-
ponding normal cell. The great bulk of these studies utilized the corres-
ponding normal adult cell, and we now begin to see how misleading this
comparison can be. It is likely that the real comparison ought to be
between the cancer cell and a normal ccll growing equally rapidly-
perhaps the embryonic cell. There is yet another point of view: what is
the definition of normality ? Some would claim that biologically speaking
the cancer cell is normal and that abnorniality resides in thc adult cell,
with its extraordinary built-in systcins of regulation and control.
What we need most is a fresh study of the chemistry of differentiation
towards much greater precision. Thcre is an analogy here. My great
predecessor at the Chester Beatty Institute, Sir Ernest Kennaway, who was
responsible for establishing that the cyclic aromatic hydrocarbons are
potent carcinogens, was responsible with his school for the isolation and
recognition of benzpyrene in carcinogenic coal tar. I would be the last to
diminish in any way this tremendous contribution. But I am struck by thc
fact that his work on the isolation of the hydrocarbons from pitch, which
required an immense amount of starting material and took many years of
labour and great ingenuity, could now, such is the advance of chemical
technology, be carried out in a single afternoon. It may be that we arc
faced by something of a similar nature but immensely more complex and
difficult, namely, the isolation and recognition of those substances in the
embryonic cell and its environs which are responsible for the proccsses of
differentiation. But immensely morc difficult as that must be, advances in
chemical technology still continuc at an unbelievable pace and it could bc
that in the next decadc or so these problems will become amenable to
solution.
In conclusion, a feature of Ciba Foundation symposia is the einergeiicc
of new ideas in discussion, which is, I think, only possible in a small closed
mecting of this type. One matter which concerns mc a great deal at the
moment is the need for more effective collaboration bctween those of us in
different laboratorics interested in this gcncral field, not only in relatioii
to the cancer problem. We all know how difficult it is in practice to establish
such co-operation, but this is perhaps something to which we should give
more thought, as a possible beneficent outcome of our present symposium.