Table Of ContentIssues and Reviews
in Teratology
Volume 1
Editorial Board
F. CLARKE FRASER
St. John's, Newfoundland, Canada
CASIMER T. GRABOWSKI
Coral Gables, Florida
ALFRED GROPP
Lubeck, West Germany
ERNEST B. HOOK
Albany, New York
NTINOS C. MYRIANTHOPOULOS
Bethesda, Maryland
WILLIAM C. SCOTT, J r.
Cincinnati, Ohio
RICHARD W. SMITH ELLS
Leeds, England
JAMES G. WILSON
Cincinnati, Ohio
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Issues and Reviews
in Teratology
Volume 1
Edited by
Harold Kalter
Children's Hospital Research Foundation and
Department oj Pediatrics
University oj Cincinnati College oj Medicine
Cincinnati, Ohio
Springer Science+Business Media, LLC
Library of Congress Cataloging in Publicatioll Data
Main entry under tirle:
Issues and reviews in teratology.
Includes bibliographical rcfCrences and index.
1. Teratogenesis. 2. Abnormalities, Human. 3. Abnormalitics (Animals) I. Kalter,
Harold.
QM691.I67 1983 616/()43 83·6323
ISBN 978-1-4615-7313-5 ISBN 978-1-4615-7311-1 (eBook)
DOI 10.1007/978-1-4615-7311-1
© 1983 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1983.
Softcover reprint ofthe hardcover Ist edition 1983
A Division of Plenum Publishing Corporation
233 Spring Street, New York, N.Y. 10013
AII rights reserved
Nu part of this book may be reproduced, stored in a rctricval system, or transmitted
in any form or by any means, electronic, mechanical, pho(ocopying, microfilming,
record ing, Of otherwîse, without writtcn permission {'ron} the Publisher
Contributors
Pamela E. Binkerd • California Primate Research Center, and Department of
Human Anatomy, School of Medicine, University of California, Davis, California
95616
A. Boue • Groupe de Recherches de Biologie Prenatale, INSERM, U.73, Paris,
France
Joelle Boue • Groupe de Recherches de Biologie Prenatale, INSERM U.73, Paris,
France
David H. Carr • Department of Anatomy, McMaster University, Hamilton,
Ontario, Canada L8N 3Z5
George P. Daston • Health Effects Research Laboratory, Environmental Protection
Agency, Research Triangle Park, North Carolina 27711
J. Feingold • Unite de Recherches de Genetique Epidemiologique, INSERM, U.155,
Paris, France
Pia Gallano • Groupe de Recherches de Biologie Prenatale, INSERM, U.73, Paris,
France
Casimer T. Grabowski • Department of Biology, University of Miami, Coral
Gables, Florida 33124
Andrew G. Hendrickx • California Primate Research Center, and Department of
Human Anatomy, School of Medicine, University of California, Davis, California
95616
Kenneth S. Hirsch • Toxicology Division, Lilly Research Laboratories, Greenfield,
Indiana 46140
Hideo Nishimura • Professor Emeritus of Anatomy, Kyoto University, Central Insti
tute for Experimental Animals, Kawasaki 213, Japan
Jon M. Rowland • California Primate Research Center, and Department of Human
Anatomy, School of Medicine, University of California, Davis, California 95616
Lauri Saxen • Department of Pathology, University of Helsinki, SF-00290 Helsinki
29, Finland
James L. Schardein • International Research and Development Corporation, Mat
tawan, Michigan 49071
William J. Scott, Jr. • Division of Teratology, Children's Hospital Research Foun
dation and the Developmental Biology Program of the University of Cincinnati, Cin
cinnati, Ohio 45229
J. L. Serre • Unite de Recherches de Genetique Epidemiologique, INSERM, U.155,
Paris, France
v
VI CONTRIBUTO RS
Michael H. L. Snow • MRC Mammalian Development Unit, Wolfson House, Uni
versity College London, London NW1 2HE, England
Charles T. Theisen • Department of Biomedical Anatomy, School of Medicine, Uni
versity of Minnesota, Duluth, Minnesota 55812
Josef Warkany • Mental Retardation Research Center, Children's Hospital
Research Foundation, and Department of Pediatrics, University of Cincinnati Col
lege of Medicine, Cincinnati 45229
On the Occasion of Josef Warkany's
80th Birthday
Probably the only unchallengeable glory of the 20th century is that the possibility
now exists of reducing the infant mortality rate nearly to the limits of further
irreducibility. And among the persons whom all nations can acclaim are those
whose lifelong task is preventing the death and lessening the suffering of children.
Beneath his casual air one senses this devotion in Josef Warkany.
He came to the United States in 1931, from the Vienna he recalls nostalgi
cally-and bitterly. He came to Cincinnati, to a new institution with a novel ori
entation, pediatric research. The Children's Hospital Research Foundation had
opened its doors only the year before, but work was already under way, new mem
bers were being recruited, and a spirit of cooperation and geniality, which still
characterizes the CHRF today, was being forged.
Those were good times for a young bachelor. He was adaptable, and friends
were made; beer and cheese were cheap, and for a pittance trolley cars made Sun
day excursions up and down the hills of the city, acquainting unattached young
foreigners with its parklike flavor.
Though it seems he had intended to stay only a year, when asked to remain
he did. The Depression was deepening; but he foresaw that central Europe, espe
cially for a Jew and humanist, would be inhospitable. No doubt, even more, he
recognized that there would be opportunity to work in an atmosphere of respect
and comradeship between young and old and between peers that did not exist at
that time in the schools, hospitals, and research departments of much of Europe.
At first he continued the studies that had prompted his invitation to Cincin
nati, the relation between levels of vitamin D and phosphorus in serum. Early,
however, another interest began to reveal itself: two papers, on chondrodystrophy
and the Laurence-Moon-Biedl syndrome, revealed an interest in congenital mor
phologic abnormalities.
Long to fascinate him were memories of villages in the Austrian Alps that
he had visited in his student days, and of the numerous inhabitants who had been
affected irremediably by environmental conditions present during their prenatal
Vll
Vlll ON THE OCCASION OF JOSEF WARKANY'S 80TH BIRTHDAY
existence~cretins: congenital idiots and dwarfs maimed before birth apparently
by lack of a simple nutritional ingredient. It was the idea of reproducing cretinism
in laboratory animals that lay behind those first experiments he undertook in the
late 1930s with Rose Cohen Nelson. What, then, was more likely to do this than
an iodine-deficient diet, which would cause goiter in the mother animal?
And what could have been more unexpected than the results they got? New
born rats with short, deformed limbs and numerous other skeletal malformations.
It was quickly established that the syndrome had nothing to do with lack of iodine;
and in a series of brilliant papers over the next 3 years were outlined the pains
taking investigations that disclosed the causative factor~riboflavin deficiency.
These are remarkable articles to read. Today we need not struggle to convince
scientists~or the public~that the environment can exert powerful influences on
development. On the contrary, it is often far too easy to do so; our problem is
perhaps credulousness on this score. But 40 years ago it was otherwise: systemic,
symmetrical, and familial malformations were thought to be genetic, and it took
careful, tedious studies to prove that such need not always be so.
The year after the first report of these results appeared, Gregg's discovery of
the teratogenic effect of rubella in children was published; then a slow trickle of
confirmatory experimental observations built up, and by the 1950s the dam was
swelled to the full, bursting in 1961 with the incredible story of thalidomide.
During these years and afterward Warkany exerted a healthy constraining
influence. Various therapeutic substances and even the common analgesic, aspirin
were discovered to be teratogenic in laboratory animals during the 1950s and some
were even found capable of deforming human embryos. But it was appreciated
that it is difficult to understand the meaning of such phenomena for most human
pregnancy; and although it was felt that indiscriminate use of drugs was undesir
able, the prevailing attitude among teratologists was not alarmist. I feel that in
part this attitude was engendered by Warkany, not altogether directly, but by his
example of conservative interpretation of experimental work, and by his knowl
edge of and respect for the past, which inculcate scepticism and moderation.
In other ways, too, he urged restraint. Believing that prematurely institu
tionalizing a scientific discipline can retard its growth, he long opposed forming a
teratology society; but when he felt the time was right, he helped create one and
was its first president. Believing that a scientific association should be strong before
undertaking the responsibility of having a journal, he discouraged the overhasty
formation of one; but when conditions favored its initiation, he spoke for and sup
ported it.
Our science is indissolubly linked to a task. It is our strength that teratology
is primarily concerned with the solution of immediate problems of human disease
and welfare, for that is the most humanizing of purposes. And this science cannot
have been more fortunate in its effort to accomplish these goals than to be guided
by so gentle and wise a man as Dr. Josef Warkany.
Preface
Teratology is at once among the oldest and youngest of human preoccupations.
Coincident with man's first observations of the stars were his recordings of human
and animal deformities. But, such aberrancies must have occurred even earlier,
for although it is one of those things-like evolution-that cannot be proven, it is
nevertheless indisputable that dysmorphogenesis must have occurred from the time
complex forms of life first arose on our planet; and that from the beginnings of
human awareness our species was conscious of such happenings. From the earliest
recordings of this fascination with the form and meaning of abnormality a tortuous
but continuous line extends to modern struggles to understand and control these
manifestations. And now, after long occupying an honorable but peripheral place
in the halls of philosophical and scientific pursuits, teratology has quite suddenly
come to take a prominent position at the hub of a complex crossroads of human
concerns.
This shift in its fortune has taken several forms. Fetal maldevelopment has
become the concern of environmentalists, activists of various persuasions, indus
trial organizations, government agencies, ethicists, parents-i.e., individuals and
groups whose actions are impelled by apprehension. Such motives are of course
not without basis; the trauma of thalidomide left a scar yet raw. For still others
clinicians, academics, experimentalists-the upsurge in the interest in fetal mal
development is at a different level, and their pursuits are broad, taking external
agents as but one of the causes of defective development. Interinvolvement between
these two spheres of concern is limited and rather unsympathetic. This is to be
decried, since they should be supporting and informing each other.
Even within the latter group, communication and mutual understanding are
poor. This is because, aside from vague purpose, little common ground is shared.
The reason for this is easy to see. Since puzzlement over abnormal prenatal devel
opment has many strands, it cannot be confined to the bounds of a single disci
pline. That is why there are no departments of teratology in medical and graduate
schools, and why its varied threads interweave with a multitude of pursuits.
Combing through a list of Teratology Society members strikingly illustrates this,
as one discovers that persons interested enough to join the Society are affiliated
IX
x PREFACE
with organizations and institutions in a great number and diversity of medical and
biological areas, cutting across and tying together all sorts of otherwise disparate
and unrelated subjects-among them, broadly defined, anatomy, embryology,
genetics, pathology, pediatrics, obstetrics, dentistry, surgery, toxicology, pharma
cology, veterinary science, psychology, radiology, neurology, epidemiology, nutri
tion, and occupational and industrial health.
These many areas of knowledge and study have given teratology a richness
of content and an ever-unfolding newness and challenge that comprise its strength;
but they have also been its weakness, in denying it a single, concentrated constit
uency, and in making for manifold misapprehensions, a babel of ends and means.
It is with the intention of providing a meeting ground for students and investiga
tors in diverse disciplines whose only common purpose is discovery of how and
why embryos become abnormal and in preventing them from doing so or in ame
liorating their condition that this series of books is initiated.
Oh, no, groans the already overburdened reader, not more books! But at least
let him be reassured that this series will strive not to be concocted according to
Voltaire's recipe, "with books one makes others," nor, as with the Summation of
St. Augustine, give rise to "two thousand fat volumes of theology." Moreover, we
would also allay the fear that Burton's plaintive observation, "they lard their lean
book with the fat of others' works," will be ignored here. And though this will be
another of the books of the making of which, as the scripturist lamented, there is
no end, yet it is to be hoped its much study will not be a weariness of the flesh.
Let us now turn to this first volume of Issues and Reviews in Teratology,
devoted to analyses, interpretations, and critiques of studies and ideas in the field
of congenital malformations, asserting, with Antonio, that "In nature there's no
blemish but the mind/None can be call'd deformed but the unkind."
