T H E L O G I C OF M O N S T E R S :
E V I D E N C E F O R I N T E R N A L C O N S T R A I N T IN D E V E L O P M E N T A N D E V O L U T I O N
by
Pere ALBERCH*
ABSTRACT
One of the most outstanding properties of natu-
ral diversity is its discreteness and order. Species can
be identified and classified because of this property.
There are two philosophical approaches to interpret the
orderliness of natural systems. These two conceptual
positions, wich I refer to as "externalist" and "inter-
nalist", prescribe drastically distinct methodological
approaches. Classical neo-Darwinism falls within the
"externalist" tradition, with its emphasis in natural
selection as the main ordering agent in evolution, this
approach basically argues that the properties of the
physical ant biotic environment determine the selective
pressures and consequently dictate which form will be
selected over others. Therefore, the discreteness and
order of natural diversity is a direct reflection of the
topography of the adaptative landscape. The interna-
list approach attributes some of the order observed in
nature as the result of the emergent properties of gene-
rative rules. I explore the latter methodological
approach introducing data from teratological systems
to illustrate how order exists, and classification is pos-
sible, in clearly non-functional systems. Subsequently
I examine the properties of pattern generating systems
and use limb development and evolution as a case study
to illustrate how we can carry out an evolutionary study
from an internalist perspective. I also discuss the struc-
ture, organization and properties of pattern-generating
systems and the role of genes in morphological evolu-
tion. I argue that is not possible to construct a genetic
theory of morphological evolution since genes and
development cannot be dissociated as different levels
of interaction. I conclude with a synthetic view of mor-
phological evolution and propose that it is as interes-
* Museo Nacional de Ciencias Naturales. J. Gutierrez Abascal, 2, 28006 Madrid, ESPAGNE.
Geobios, m6moire sp6cial n 12 p. 21-57, 19 fig., 2 pl.
Rt;SUMI~
Une des propri6tds les plus 6videntes de la diver-
sit6 naturelle est sa discontinuit6 et son organisation.
Les esp6ces peuvent atre identifi6es et class6es ~ cause
de cette propri6t6. Philosophiquement, il existe deux
approches qui permettent d'interprdter cette organisa-
tion des syst6mes naturels. Ces deux conceptions, que
je qualifie d'"externaliste" et d'"internaliste" impo-
sent des m6thodes d'approche tr6s diff6rentes. Avec la
sdlection naturelle comme principal agent d'organisa-
tion de l'6volution, le n6o-Darwinisme classique se rap-
porte/~ la tradition externaliste. Cette approche admet
que les param6tres physiques et biotiques de l'environ-
nement d6terminent seuls la pression de s61ection et,
en cons6quence, ddterminent quelle forme sera sdlec-
tionn6e. Ainsi, la discontinuit6 et l'ordre de la diver-
sit6 naturelle sont le reflet direct de la topographic du
paysage adaptatif. L'approche internaliste attribue une
part de l'ordre naturel /~ l'6mergence de propri6tds
intrins6ques au matdriel vivant. J'examine cette derni6re
approche/t partir de donn6es tirdes de syst6mes tdra-
tologiques pour illustrer comment cet ordre se mani-
feste, et quelle classification est possible dans des systb-
mes clairement non fonctionnels. Ensuite, j'examine
les propri6t6s de systbmes g6n6rateurs et j'utilise le d6ve-
loppement et l'6volution des membres pour illustrer
comment on peut mener une 6rude 6volutive dans une
perspective internaliste. Je discute aussi la structure,
l'organisation et les propri6t6s des syst6mes g6ndrateurs
ainsi que le r61e des g6nes dans l'6volution morpholo-
gique. J'admets qu'il n'est pas possible de construire
une th6orie g6ndtique de l'6volution morphologique
puisque g6nes et d6veloppement ne peuvent atre disso-
cids en rant que niveaux d'interaction diff6rents. Je ter-
Lyon, 1989
 m 22 m

PLATE 1

Plate 1 - - Illustrations of animal diversily.

(Clockwise from upper left) Paleolithic cave paintings. Roman mosaics. Morphological variation in sterns (from
a contemporary field guide). R. Savery "Landschaft mit V6geln" (early 17th century) Kunsthistorisches Museum,
Vienna.
Illustrations de la diversit~ animale.
De gauche/t droite et de bas en haut : peinture rupestre pal6olithique ; mosaiques romaines ; tableau de R. Savery
"Landschaft mit V6geln" (ddbut du 17% Kunsthistorisches Museum, Vienna) ; variation morphologique chez les
sternes.
 m 23
ting and illuminating to focus on invariance as on diver-
sity. Similarly, monsters are a good system to study the
internal properties of generative rules. They represent
forms which lack adaptative function while preserving
structural order. An analysis of monsters, is a study
of "pure f o r m " in the classical Naturphilosophie sense.
There is an internal logic to the genesis and transfor-
mation and in that logic we may learn about the cons-
traints on the normal.
KEY-WORDS : ONTOGENY, PHYLOGENY, AMPHIBIAN.
MOTS-CLI~S : ONTOGENI~SE, PHYLOGENI~SE, AMPHIBIENS.
The earliest signs of human civilization - the Paleo-
lithic cave paintings - already reveal the interest of Man
in the diversity of organic form. Ever since - f r o m the
mosaics of Pompei to the paintings of Brueghel and
Savery ; f r o m Pliny's Natural History to contemporary
field guides, passing through the rich tradition of
Medieval Bestiaries - artists and scientists alike have
been fascinated with the enormous variety of plant and
animal life (pl. 1).
We are so bewildered by the diversity of nature
that we often forget that the world could have been of
a very different shape. H u m a n imagination has been
a fertile source of new forms - forms that could have
existed but were not to be. Even in the early cave pain-
tings we already find composite creatures, human-beast
hydrids resulting from human fantasy. Mythology has
been rich in generating new morphologies, such as mer-
maids, centaurs and unicorns. Certain artists, f r o m
Hieronymus Bosch to such modern surrealists as J o a n
Miro have specifically attempted to create new mor-
phological universes independent of external reference
(pl. 2).
A comparison between the forms illustrated in pla-
tes 1 and 2 makes obvious one the most fundamental
questions in evolutionary biology, one that underlies
the whole field : Why do we observe certain forms in
nature and no others ? Why d o n ' t we find mermaids
or multi-headed dragons ?
The idea of limited diversity can be pictorially des-
cribed using the concept of phenotypic space (Alberch
1980). Let us assume that any f o r m can be completely
described by a set of measurements corresponding to
a point in a multidimensional space (for simplicity, I
will reduce this analysis to two dimensions, x and y)
(fig. 1). The phenotypic space is, thus, the set of all
m
mine par une vision synthdtique de l'6volution morpho-
logique et sugg6re qu'il est tout aussi fructueux de s'in-
tdresser/~ l'invariance qu'~ la diversit6. Les monstres
sont un bon mod61e pour comprendre les propridt6s
internes des systbmes gdn6rateurs. Ils correspondent/~
des formes qui n ' o n t pas de fonction adaptative, mais
qui conservent l'ordre structural. Une analyse des
monstruosit6s est une ~tude de la " f o r m e pure" au sens
classique de Naturphilosophie. I1 existe une logique
dans la gen6se et la transformation des monstruosit6s
qui nous renseigne sur les contraintes qui existent dans
les cas normaux.
possible forms, i.e. any combination of x and y values.
Each individual form corresponds to a point in this
space. If we were to plot all observed phenotypes, inclu-
ding malformations that die during embryonic or post
embryonic development, we would find that the phe-
notypic space is not uniformly filled by points. Instead,
populations of forms are clustered and separated from
others by empty regions. These clusters of points would
correspond to species, polymorphic forms or even clas-
ses of teratologies (e.g. wingless mutants in chicks or
homoeotic mutations in Drosophila).
Traditionnally, biologists in general and evolutio-
nists in particular have focused on patterns of variabi-
lity. That is, the shape and distribution of the clouds
of points in phenotypic space. In this paper, I am more
concerned about the empty spaces, about the morpho-
logies that, although conceivable are not realized. These
discontinuities in phenotypic space account for the
order observed in nature and they are the reason why
a classification of forms is possible. Forms can only
be described and arranged in a hierarchical classifica-
tion (order, family, genus, species...) if they are dis-
crete. If populations of forms smoothly blended one
into another through a series of intermediates, any mor-
phological diagnosis of species would be arbitrary.
The existence of continuous variation in m o r p h o -
logy is a position defended by strict Darwinism, roo-
ted in the traditional Western view of nature as a con-
tinuum (see reviews by Lovejoy 1936 ; Mendelsohn
1980) and exemplified by the following quotes :
" ( T h e term species is) arbitrarily given, for the
sake of convenience, to a set of individuals closely
resembling each other ; it does not essentially differ
from the term variety, which is given to less distinct
and more fluctuating forms. The term variety, again,
 m 24 m

PLATE 2
Plate 2 - - Imaginary creatures.
(Clockwise from upper left). "The Sorcerer" or "Horned God", Trois Fr~res Cave (Upper Paleolithic) ; Medieval
dragon (Frontal dels Arcangels, 13 th century, Museu d'Art de Catalunya) ; Drawings from Codex Seraphinianus
(Franco Maria Ricci editor, 1981) ; Joan Miro, lithograph from the "Homenatge a Joan Prats" series, 1971).
Crl~atures imaginaires.
De gauche ~l droite et de bas en haut : "le sorcier" ou "dieu cornu", Grotte des Trois Fr6res (Pal6olithique sup&
rieur) ; dragon m~di6val (Frontal dels Arcangels, 13e si6cle, Museum d'Art de Catalunya) ; Joan Miro, lithographie
"Homenatge a Joan Prats", 1971 ; dessins tir6s de Codex Seraphinianus (Franco Maria Ricci 6diteur, 1981).
 -- 25 --

in comparison with mere individual differences, is also Empirical data, however, do not support this prin-
applied arbitrarily, for convenience sake" (Darwin ciple of continuity and suggest that species are homeos-
1859, p. 42). tatic and discontinuous entities. A fact that, in most
instances, allows for the construction of an unambi-
"The word species is simply a term of convenience,
gous taxonomy. Therefore, I will begin this essay by
including such members of a group similar to each
examining the mechanisms that have been postulated
other as are tangibly different from others, and are not
to be responsible for these gaps in phenotypic space.
known to be connected with these by intermediate
forms. Such connecting links we m a y suppose in all
cases" (Jordan 1905, p. 293).

Fig. 1 - - A phenotypic space is the set of all possible phenotypes.

This diagram assumes that the morphology of an organism
can be completely defined by the measurement of two traits,
x and y. Each point corresponds to a specific morphology.
C,I ---- D Not all possible phenotypes are found. The distribution of
/~" I , "l points in non-uniform. Clusters of points could correspond
/ ~ I * ]
6 , ~
to species (e.g. A and E), polymorphic, or closely related,
>- / ""...'? ., t-, " ;" species (e.g. C1 and C2) which are not separated by dis-
,. ".'.'-..- --~- c,2 - tinct morphological discontinuities, or classes of teratolo-
F- \
gies (e.g. D and B).
\~* ",,,~**

<~ .... ", , ' * I l l ; " * r

U n espaee ph~notypique est l'ensemble de tous les ph~uoty-
Fr" \* p .. /
pes possibles.
Ce diagramme montre que la morphologie d ' u n organism
/ . : - . . \ \ I I * . . . ':, w
. - .
\ peut ~tre compl6tement d6finie par la mesure de deux carac-
~. ::lg, 1 t6res, x et y. Chaque point correspond ~. une morphologie
.,* .1 t / ' - ;'" ~* /;
particuli6re. Tousles ph6notypes possibles ne sont pas r6a-
"-'_L \ . \---" "/
tA " .', ' ":" E lis6s. La distribution des points n'est pas uniforme. Les
ensembles de points pourraient correspondre ~t des esp6-
ces distinctes (e.g. A et E), fi des esp6ces polymorphiques
ou 6troitement apparent6es (e.g. C1 et C2) qui ne seraient
pas sdpar6es par des discontinuitdes morphologiques, ou
TRAIT X enfin ~ des types de tdratologies (e.g. B et D).

A - ORIGINS OF ORDER AND DISCONTINUITY IN N A T U R E

Historically there have been two distinct approa- through the elimination of less fitted intermediate
ches to the question of why certain forms are not found forms. In this case, and in agreement with the princi-
in nature. They reflect two qualitatively different ways ple of continuity in nature, phenotypic space is effec-
of seeing the organic world. I purposely caricature the tively continuous prior to the action of selection. I refer
two positions by emphasizing their more extreme to this approach as functionalist (after Gould 1986) or
forms. At this point, I am not interested in doing an as "externalist" in the sense that the observed order
exhaustive review of the subject. Rather, I want to high- in nature is caused by agents external to the organism.
light the methodological consequences of taking each
of these philosophical stands. The origins of this school of thought can be tra-
ced back to Cuvier. In his influential writings, Cuvier
coupled the concept that functional demands essentially
1. THE EXTERNALIST/FUNCTIONALIST APPROACH
shape morphology with the hypothesis that disconti-
This is basically the thesis defended by Darwin and nuity in the history of life is the result of externally
Jordan in the quotes cited above. It claims that nature determined catastrophic events (see Appel 1987 for a
is essentially continuous. This is a philosophical rather historical review of this issue).
than empirical position. Intermediate forms, even if not
The externalist world view is so predominant in
found today, are considered possible.
the field of evolutionary morphology that it is not
Their absence can be explained by invoking his- usually made explicit. This approach views directiona-
torical contingency (e.g. they existed in the past but lity and order as imposed by natural selection acting
have disappeared since then, or, alternatively, the on variation (noise) generated by genetic mutation.
system has yet to evolve into this particular region of Selective pressures are a function of the physical and
phenotypic space). In addition, Darwinism claims that biotic factors of the environment in which the organism
natural selection acts as the main ordering agent
 - -
ELECTION (direction)
PHENOTYPEI EVOLUTION
MUTATION (noise)
is found. For example, gills are considered adaptations
to aquatic breathing as long as there is water in the
pond. Therefore, and this is what I mean by the term
externalist, the motor of evolutionary change and diver-
sification (selection) depends on factors external to the
organism (fig. 2).
This scheme defines a research program which
focuses either on problems of adaptation or on the
population dynamics of the system. Research on adap-
tation is essentially a static study of how well a parti-
cular design performs in a particular environment rela-
tive to alternative designs also found in the population,
in an attempt to identify selective pressures that may
account for its present state. These studies often make
use of machine-organism analogies and employ con-
cepts of optimization borrowed from economics or
engineering models (e.g. Dullemeijer & Barel 1977).
A central metaphor in the externalist approach is
the concept of the adaptive landscape (Wright 1932).
An adaptive landscape is basically a phenotypic space
in which a fitness value is associated with every possi-
ble phenotype [fitness value of phenotype (x, y) =
height of landscape at (x, y)]. The topography of the
landscape is, however, externally defined. As the envi-
ronment changes, the relative fitness of the various phe-
notypes is affected, a fact depicted as a change in the
adaptive landscape. Some adaptive peaks disappear
while new ones form. Organisms evolve by climbing
towards the top of the nearest peak. Therefore, the
ordered variation observed in nature is a reflection of
the topography of the adaptive landscape. This pers-
pective, interpreting order in terms of the properties
of the adaptive landscape, is clearly illustrated by the
following quote t~rom one of the fathers of the nee-
Darwinian synthesis, the geneticiat Theodosius Dobz-
hansky (1951 ; pp. 9-10) : " T h e enormous diversity of
organisms may be envisaged as correlated with the
immense variety of environments and of ecological
niches which exist on earth. But the variety of ecological
2 6 - -
Fig. 2 - - E x t e r u a l i s t s c h e m e .
Phenotypic evolution is the result of the interaction of deter-
ministic natural selection acting on variation generated by
mutation.
S c h 6 m a externaliste.
L'evolution phenotypique est le resultat de l'interaction
entre la selection naturelle d6terministe et la variation due
aux mutations.
niches is not only immense, it is also discontinuous...
The adaptive peaks and valleys are not interspersed at
random. " A d j a c e n t " adaptive peaks are arranged in
groups, which may be likened to mountain ranges in
which the separate pinnacles are divided by relatively
shallow notches. Thus, the ecological niche occupied
by the species " l i o n " is relatively much closer to those
occupied by tiger, puma and leopard than to those
occupied by wolf, coyote, and jackal. The feline adap-
tive peaks form a group different from the group of
canine " p e a k s " . . . The hierarchic nature of the biolo-
gical classification reflects the ascertainable disconti-
nuity of adaptive niches, in other words, the disconti-
nuity of ways and means by which organisms that inha-
bit the world derive their livelihood from the
environment."
To Dobzhansky, order and hierarchical oganiza-
tion are imposed by the discontinuities in ecological
space ; a perfect example of the externalist approach
to phenotypic evolution. It is unlikely that Dobzhansky
himself would subscribe to such a radical position.
Since, although there is ample empirical evidence that
ecological diversity plays a key role in structuring pat-
terns of faunal and floral diversity [e.g. Lack (1947)
on the Galapagos (Darwin's) finches ; Williams (1972,
1983) on the West Indian Lizards of the genus A n o -
lis ; or the abundant work on coevolution), one can-
not ignore the role of history. After all, felines are simi-
lar not only because they occupy similar ecological
niches, but also because they share a common ances-
tor. In fact, it could be argued that it is because felines
represent variations within a conserved body plan that
they are constrained to a subset of similar ecological
niches. Dobzhansky's statement, nevertheless, clearly
illustrates the nee-Darwinian tendency to disregard his-
tory in favor of adaptive explanations (Gould 1983).
In this tradition, internal factors, often equated with
lack of genetic variability for the trait, may slow down
the evolutionary process but if selective pressures are
strong enough - and population size sufficiently large
 --
they will eventually overcome any developmen-
tal/genetic constraint (e.g. Charlesworth et alii 1982 ;
Lande 1986).
2. THE INTERNALIST (STRUCTURALIST)APPROACH
History carries with it a set of system specific cons-
traints, which in turn can bias the future evolution of
the system. I refer to this philosophical tradition as
internalist. This approach, instead of focusing on the
external forces of evolution, emphasizes the role of
internal factors. Internalist theories have a long, but
minority, tradition in evolutionary biology (e.g. Berg-
son 1907; Berg 1926; Osborn 1934; Schindewolf
1936, 1950 ; Goldschmidt 1940 ; Cuenot 1951 ; Wad-
dington 1957 ; Cannon 1958 ; Grass6 1970 ; Saunders
& H o 1976; Ho & Saunders 1979; Riedl 1979;
Alberch 1980 ; Rachootin & T h o m s o n 1981 ; Webster
& Goodwin 1982 ; Wake & Larson 1987, have defen-
ded the role of internal factOrs in evolutionary proces-
ses f r o m a variety of perspectives). Gould (1986) has
recently referred to this position as "structuralist" in
reference to the theories of Geoffroy St. Hilaire. Given
the recent, more restricted usage of the term in anth-
ropology, linguistics and, even evolutionary biology
(e.g. Lauder, 1981 ; Webster & Goodwin 1982), I pre-
fer to use the more descriptive, and philosophically less
loaded, term of "internalist".
The roots of the internalist perspective predate
Darwinism and they can be found in the ideas of
Romantic and transcendental morphologists such as
Goethe, G e o f f r o y St Hilaire and Owen to name only
three influential figures from three different countries.
These authors, and m a n y others (see historical reviews
by Russel 1916 and Appel 1987), searched for invarian-
ces and universal rules of organization in support of
their basic tenet which argues that form is primary over
function and that a "unity of plan" underlies the diver-
sity observed in nature.
These ideas can be translated, in a modern con-
text, to m e a n that the regularities and trends observed
in phylogeny are a reflection of a conserved set of
pattern-generating rules (Oster & Alberch 1982 ; Good-
win 1982). These internal rules of development define
the realm of possible variation and place limits on the
PHENOTYPES
PERTURBATION SYSTEM
27 m
process of adaptation. The internalist approach is dia-
grammatically depicted in fig. 3. In it, the genetic and
developmental interactions that are responsible for the
genesis of biological f o r m are illustrated as a "black
b o x " . More information on the nature of specific pat-
tern generating systems can be found in O s t e r &
Alberch (1982), and specific examples are discussed in
Appendix I. At this point it suffices to state that f o r m
is the product of physico-chemical interactions at the
genetic and epigenetic levels.
The internalist approach assumes, and this is a key
assumption, that morphological diversity is generated
by perturbations in parameter values (such as rates of
diffusion, mitotic rate, cell adhesion, etc.) while the
structure of the interactions a m o n g the components
remains constant. For example, a specific enzyme will
bond to its substrate with an affinity that can be quan-
titatively modulated by either a genetic mutation alte-
ring the amino acid sequence at the binding site or envi-
ronmental parameters, such as temperature, affecting
rate of reaction. The interaction between the specific
enzyme and its substrate is assumed to remain inva-
riant, although the binding affinity could be zero.
Given this assumption, even if the parameters of the
system are randomly perturbed, by either genetic muta-
tion, environmental variance or experimental manipu-
lation during development, the system will generate a
limited and discrete subset of phenotypes. Thus, the
realm of possible forms is a property of the internal
structure of the system.
Returning to the phenotypic space in figure 1,
internalist theory argues that even in the absence of
selection naturally occuring morphologies would be
clumped and gaps would be prominent in the distribu-
tion of morphologies. In its purest sense, the interna-
list approach is not interested in the problem of adap-
tation. In fact, as I will argue below, one of the best
examples of internally defined order can be found in the
organization observed in the appearance of gross mal-
formations, either experimentally induced or the pro-
duct of a genetic mutation. The internalist approach is
fundamentally typological. Instead of focusing on popu-
lation dynamics, it is concerned about the origin and
properties of types, the limits of form, and the nature
of the rules that are responsible for this ordered pattern.
Fig. 3 -- Internalist scheme.
Perturbations resulting from genetic mutation or environ-
mental impact are "filtered" through the dynamics of a
pattern-generating system. The internal structure of the
developmental system defines a finite and discrete set of
possible outcomes (phenotypes)even if the sources of per-
turbation are random.
Schema internaliste.
Les perturbations issues de mutations g6n6tiques ou de Fin-
fluence de l'environnement sont filtr6es par la dynamique
d'un syst~me"structurant". Ainsi, la structure m~med'un
d6veloppement impose un nombre fini et discret d'abou-
tissements possibles (ph6notypes), m~me si les sources de
perturbations sont al~atoires.
 --
In this paper, i explore the implications of this
approach and I propose a logically consistent, alter-
native way of studying morphological evolution - a
method rooted in an understanding of the properties
of organisms rather than of the properties of the envi-
ronment. I focus on the internal rules that control the
appearance of morphological variation, on the mecha-
nistic basis of such rules and on the evolutionary con-
i sequences of this internally determined order. I need
to emphasize that this approach is not mutually exclu-
sive to the externalist or adaptationist approach (e.g. see
Larson & Wake, 1987, for an attempt to integrate both
approaches). The perspective that I defend here simply
focuses on different issues, poses different questions and
prescribes a qualitatively different research program.
B. MONSTERS AS EVIDENCE FOR I N T E R N A L C O N S T R A I N T IN D E V E L O P M E N T AND E V O L U T I O N
To explore the role of internal factors in evolu-
tion we need first to resolve the issue of how much of
the observed pattern is internally generated. After dis-
secting internally from externally determined order, we
can proceed to address the specific genetic and deve-
lopmental mechanisms responsible for internal cons-
traint in ontogeny and phylogeny. To study the first
issue we need to carry out an analysis of patterns of
variation, while to address the second we have to
understand the mechanisms that control the genesis of
form during development.
When studying natural systems it is often difficult
to distinguish between the action of selection and the
effect of internal constraint. For this reason, I propose
that it may be advantageous to turn to non-functional,
grossly maladapted, teratologies when studying the pro-
perties of internal factors in evolution. These major
deviations from normal development result in forms
that are often lethal, and always significantly less well
adapted than their progenitors. Therefore, one expects
monsters to be consistently eliminated by selection. This
is a useful property because if, in spite of very strong
negative selection, teratologies are generated in a dis-
crete and recurrent manner, this order has to be a reflec-
tion of the internal properties of the developmental
system.
This interest in teratology contrasts with the bad
reputation that monsters have traditionally enjoyed in
the Darwinian literature. From an externalist perspec-
tive, teratologies as non-functional entities are evolu-
tionary deads ends and, as such unworthy of study. I
emphasize that I introduce teratologies only as model
systems to study the patterning generated by develop-
mental properties. Unlike the classical "hopeful mons-
ters" of Goldschmidt (1940), I do not contend that tera-
tologies are variation with evolutionary potential. In
fact, I assume them to be lethal in most cases. The dis-
28 --
I focus on the evolution of form at a strictly deve-
lopmental level. It is, however, important to recognize
that the internalist philosophy, with its emphasis on the
structure of interactions as a system of constraints, is
not the exclusive domain of developmental biology. For
example, Garcia-Bellido (1983, 1986), Kauffman (1983)
and Agur & Kerszberg (1987) present evolutionary
models based on the properties of regulatory networks
of genetic interactions. Similarly, Liem (1980) and Lau-
der (1981) have explicitely used an internalist approach
to study the evolutionary properties of systems of func-
tional interactions, and Edelman (1987) incorporates
the issue of developmental constraint emerging from
epigenetic interactions in a general theory of brain
function.
continuity of the evolutionary process defended by
Goldschmidt and others is an issue that I will not dis-
cuss in this paper.
1. PROPERTIES OF TERATOLOGICALSYSTEMS
Teratologies are a superb document of the poten-
tiality of a given developmental process. In spite of
strong negative selection, teratologies are not only gene-
rated in an organized and discrete manner but they also
exhibit generalized transformational rules. These pro-
perties are not exclusive to teratology ; rather they are
general properties of all developmental systems. There
are numerous examples illustrating parallel patterns of
intra-populational and inter-specific morphological
variation (e.g. Vavilov 1922 ; Spurway 1949 ; Raikow
1983 ; Alberch 1983 ; Garcia-Bellido 1983 ; Shubin &
Alberch in press). These properties are, however, bet-
ter illustrated using data from pathological systems.
a. Ordered and discrete generation
Teratologies are generated in an organized man-
ner. Certain forms are more likely to appear than
others. I discussed this property in Alberch (1980) and
gave several examples ranging from the variation in the
gross anatomy of the aortic arches in rabbits to the rates
of occurrence of homoeotic transformations in Dro-
sophila. A similar pattern is evidenced even at the level
of " e r r o r s " in cytodifferentiation as observed in trans-
determination experiments (fig. 4a). Imaginal disks
with well defined developmental fates can be tricked
into differientiating into another type of tissue when
cultured for long periods of time. The transformations
observed, however, are not chaotic. For example, if a
prospective genital cell makes a mistake, it will most
likely produce a leg or a head-antenna tissue type, or
with a lower probability a palp. It will never give rise
 -- 29 --

A B

Genital

Head-
leg antenna
disc disc

~ Wing disc

l
Thorax disc

Fig. 4 - - Ordered transition in developmental states.

A. Pathways of transdetermination in imaginal discs in Drosophila (from Gilbert 1985). B. Pathways of transdetermination in human
epithelial tissues (from Slack 1985). Thick arrows denote the most frequently observed events, while thin arrows depict rare ones.
Lack of arrows between differentiated states indicates that the transformation is extremely rare.
Agencement ordonn~ des ~tats dn d~veloppement.
A. Itin~raire de transd6termination des disques imaginaux chez Drosophila (d'apr~s Gilbert 1985). B. Itin&aire de transd~termina-
tion des tissus 6pithdliaux chez l'homme (d'apr6s Slack 1985). Les flbches @aisses indiquent les transformations les plus fr6quem-
ment observ6es tandis que les fl6ches minces indiquent les plus rares. L'absence de fl6che entre deux 6tats indique que la transforma-
tion est extr~mement rare.

to a wing o r a t h o r a x . Slack (1985) has recently revie-
wed a similar set o f restricted cellular t r a n s f o r m a t i o n s
in h u m a n tissues (fig. 4b). T h e general result is t h a t
d e v e l o p m e n t a l p a t h w a y s when p e r t u r b e d b y genetic
m u t a t i o n o r e x p e r i m e n t a l m a n i p u l a t i o n can u n d e r g o
o n l y a l i m i t e d set o f t r a n s f o r m a t i o n s a n d certain deve-
l o p m e n t a l switches are m o r e likely to occur t h a n others.
This p r o p e r t y was e m p h a s i z e d a n d a l l e g o r i c a l l y depic-
ted in the " e p i g e n e t i c l a n s c a p e s " o f W a d d i n g t o n
(1957).
I n t r i n s i c o r d e r in the g e n e r a t i o n o f m o n s t r o s i t i e s
was discussed in the p i o n n e e r i n g w o r k s o f the fathers
o f m o d e r n t e r a t o l o g y , Etienne a n d Isidore G e o f f r o y
Saint H i l a i r e in the early a n d m i d n i n e t e e n t h c e n t u r y .
T h r o u g h an extensive survey, these authors noticed that
t e r a t o l o g i c a l f o r m s were n o t o n l y discrete a n d recur-
rent, a fact t h a t allowed t h e m to be d e s c r i b e d a n d dia-
gnosed, b u t they also c o u l d be classified in a h i e r a r -
chical m a n n e r a n a l o g o u s to the L i n n e a n system o f clas-
sification f o r n a t u r a l species ( e . g . I . G e o f f r o y Saint
H i l a i r e 1936 ; fig. 5). E v e r y m o n s t r o s i t y c o u l d be assi-
gned to a class and within its class to an order, a family,
a genus and, in the w o r k o f E. G e o f f r o y Saint Hilaire,
a species. His son, I s i d o r e o n l y classified t e r a t o l o g i e s
to the generic level in his c o m p r e h e n s i v e treatise entit-
led " H i s t o i r e Gdn6rale et Particuli6re des A n o m a l i e s
chez l ' H o m m e et les A n i m a u x . . . " (1836), which is
widely r e g a r d e d as the w o r k which set up the f o u n d a -
tions o f m o d e r n scientific research in t e r a t o l o g y . T h e
classification p r o p o s e d b y I. G e o f f r o y St. H i l a i r e was
n o t s u p p o s e d to reflect lineage r e l a t i o n s h i p s , i n s t e a d
it w o u l d be m o r e a n a l o g o u s to a p e r i o d i c table o f che-
mical elements or a c l a s s i f i c a t i o n o f crystal types.
On the absence of triple monsters
A n a l y s i s o f the diversity f o u n d in t e r a t o l o g i c a l
f o r m s reveals the fact t h a t n o t all possible t e r a t o l o g i e s
are g e n e r a t e d . F o r e x a m p l e , I. G e o f f r o y Saint H i l a i r e
(1836, vol. 2, chap. 12) p o i n t s out t h a t two h e a d e d
m o n s t e r s (i.e. b i f u r c a t i o n o f the a n t e r i o r region o f the
p r i m a r y axis o f the b o d y ) are relatively c o m m o n in all
g r o u p s o f vertebrates f r o m fish to h u m a n s (see below).
C o n s e r v e l y , t h r e e - h e a d e d m o r p h o l o g i e s are e x t r e m e l y
 -- 30 --

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~ ~-~ ~ ~ . ~ ~'~ ~--~_~ . . ~ .
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 m31
rare in nature. A review of the literature failed to turn
up any convincing case of a monster in which a single
body axis trifurcates anteriorly into three heads. I.
Geoffroy St. Hilaire summarized the classical literature
and concluded that with only two exceptions all the few
other reported cases are at best doubtful, and most
Medieval descriptions of three headed animales are
clearly the products of fantasy (like the tricephalous
human reported by Bartholin ; born with three heads
- one human, the other a wolf's an the third a bloody
mass without skin - was not only born alive, but " i t "
only expired after appearing in front of the city Senate
to make a series of sinister predictions). Of the relia-
ble descriptions of three - headed monsters, the Italian
physicians Reina and Galvagni provide the best des-
cription (Sopra un feto h u m a n o trieefalo (1832) cited
in I.G. St. Hilaire, p. 341 ; see figure in Gould & Pyle
1937, p. 167). Based on Reina and Galvagni's detailed
dissection, it is clear, however, that this specimen is only
an apparent trifurcation, since the fetus had two com-
plete spinal chords running parallel to each other. One
of the two b o d y axes bifurcated to generate the extra,
third, head. The absence of triple monsters was also
noted by one of the pionners of G e r m a n comparative
anatomy and embryology, Meckel, who in the early
1800's elevated this fact to the category of law. Mec-
: kel claimed that monsters exhibiting extra elements
were always generated by binary duplication of parts
(cited in I. Geoffroy St. Hilaire 1836, p. 331-332). Stoc-
kard (1921) reported on an extensive study of naturally
and experimentally induced " d o u b l e m o n s t e r s " in the
fish Fundulus. Out of several hundred specimens, 150
double monsters were observed. Only one triplet was
generated, which consisted of a combination of one
embryo and a double headed monster (i.e. analogous
to the case reported by Reina & Galvagni 1832).
I only mention the absence of three-headed mor-
phologies, but the same kind of analysis could be
applied to any other syndrome or abnormality. For
example, I have recently discussed digital anomalies in
domestic breeds of dogs (Alberch 1986) ; a case in
which perhaps there are no strictly forbiden m o r p h o -
logies but where clear trends in the generation of varia-
tion can be observed.
In conclusion, not all monstrosities are possible
and a m o n g the possible, certain ones are more likely
to be generated than others. In addition, observed mor-
phologies can be arranged in unambigous graded
sequences. Therefore, teratological f o r m m a y not
necessarily be discrete but it is always orderly.
b. Transpecifie parallelism in the genesis of teratolo-
gical forms
Similar trends in the kinds of monstrosities gene-
rated are encountered in different, unrelated, species.
--
This is illustrated by the fact that I. Geoffroy St.
Hilaire's classification, as many other subsequent ones,
was not based on any particular species. Any vertebrate
monster could be fitted into his scheme. For example,
as mentionned above, bicephalous monsters are found
in most vertebrate species (fig. 6). Similarly, a cyclops
exhibits the same characteristic morphological featu-
res, regardless of the species in which it appears (Adel-
man 1936). Sometimes this morphological invariance
can transcend the vertebrate-invertebrate boundary ;
for example, Ranzi (1957) reports a case of cyclopia
in the squid. I refer to this organizational invariance
across species boundaries as transpecific parallelism.
It suggests that the rules that control the expression of
abnormal forms exist above any historical considera-
tions associated with lineage relationships.
This point can be further illustrated using the tho-
rough anatomical study of Wright & Wagner (1925).
As part of a research p r o g r a m on the genetic basis of
morphological abnormalities, Wright & Wagner asso-
ciates were able to study over 300 guinea pig mutants
which exhibited a variety of malformations. Wright &
Wagner (1925) assigned these teratologies to the family
of monsters which I. G e o f f r o y St. Hilaire had termed
" o t o c e p h a l i e n " . The affected specimens could be
arranged along a gradient of increasingly severe mal-
formations belonging to the various types ( " g e n e r a " )
described by Geoffroy St. Hilaire. The less affected spe-
cimens (grade 1) had a slightly shortened lower jaw with
loss of the incisors. Increasingly malformed foetuses
included progressive reduction of head structures, such
as loss of nostrils, the formation of a univentricular
telencephalon, and associated cyclopia. The sequence
of loss of structures was, however, highly invariant and
the immense majority of the specimens studied could
be classified along the series illustrated in fig. 7.
The point relevant to this discussion, however, is
that the observed morphologies are not exclusive to gui-
nea pigs. Numerous cases of cyclopia, otocephaly and
anencephaly have been reported in the literature. The
morphological patterns described are essentially the
same in all vertebrates (see review by Adelmann 1936).
Stockard (1921) pointed out that although the spe-
cific morphology of the malformation obtained is iden-
tical, there are species-specific differences in the pro-
bability of occurrence of any given teratology. In other
words, certain teratologies are commonly encountered
in certain species while rare in others. For example,
double monsters are c o m m o n in the trout, while they
are a lot more difficult to obtain in the minnow Fun-
dulus. Similarly, Stephens & Shepard (1983) reported
different incidences of specific limb teratologies in
various human ethnic groups. Similarly, it is well
known that there is a hereditary component in the for-
mation of monozygotic twins in humans (e.g. Bulmer,
 -- 32 --

0 d

,i -~..'~'..:":~:~';~;~iii.;:........-....T;7:'"::'.'::':':'::.::'?:"~ : ~
:~/:.!.:.~' " " ......... : ' ii'2:.!~,~-~-~~!~

, ~

C f

Fig. 6 - - Ordered variation and transpecific parallelism in the occurrence of monstrosities.

The three basic types of conjoined twins ("double monsters") in humans (a-c) and in the fish Fundulus (d-f). Duplication results
from anterior bifurcation of the body axis (a, d). Fully developped twins can " f u s e " through any region in their body but, most
frequently, fusion occurs in the abdominal region (b, e). Parasitic twins are also observed in all vertebrate taxa (e. g. c, f). Drawn
from photographs in Stockard (1921) (a, b, d, e, f) and Drimmer (1973) (c).
Variation ordonn~e et paraIWiisme transp~cifique de monstruosit~s.
Les trois types fondamentaux de jumeaux siamois ("monstres doubles") chez l'homme (a.-c) et chez le poisson Fundulus ~d - f).
La duplication r6sulte d'une bifurcation antdrieure de l'axe du corps (a, d). Des jumeaux compl~tement d~velopp6s peuvent iusion-
ner par n'importe quelle partie de leurs corps, mais le plus souvent la fusion concerne ta r6gion abdominale (b, e). Des jumeaux
parasites existent aussi dans tousles taxons de vert~br6s (c, 0- Dessins a, b, d, e, f d'apr~s des photographies de Stockard (1921) ;
dessin c d'apr6s Drimmer (1973).
 --33 m
1970). Monozygotic twins, resulting from an abnormal
fission of the early blastocysts, are conceptually homo-
logous to any other teratology (except in armadillos in
which polyembryony is the norm rather than be
exception).
The recurrence of similar teratologies in different
species suggests that the structure of developmental
interactions responsible for the generation of a parti-
cular structure (e.g. vertebrate head or limb) has remai-
ned invariant throughout phylogeny. The species - or
even population - specific differences in the probabi-
lity of occurrence of a particular teratology indicates
that there is a genetic ( = lineage dependent) compo-
nent that determines that, at a particular state, certain
transformations are more likely than others. These
species-specific tendencies can be understood using the
conceptual framework outlined in Oster & Alberch
(1982). The probability of a particular transformation
in determined by the position of the system in para-
meter space (Appendix II).
2. I N T E R P R E T A T I O N OF T H E O R D E R OBSERVED IN
TERATOLOGY
A genetic mutation can a priori result in any kind
of morphology. There is no justification at the genetic
level to explain the fact that a two-headed morphology
is of much more c o m m o n occurrence than a three-
headed one. (Since they are both maladaptive, and
usually lethal, " m u t a t i o n s " , the effects of selection can
be ruled out as an explanation in this particular case).
Similarly it is very unlikely that the so-called "cyclo-
p i a " mutations encountered throughout the vertebra-
tes have the same genetic identity, in the sense of invol-
ving changes in the same region of the DNA. The fact
that different mutations can result in the same mor-
phological outcome has been clearly demonstrated. For
example, there is a variety of mutations resulting in win-
glessness in chickens (Waters & Bywaters 1943 ; Lan-
caster 1968 ; Prahlad et alii 1979). Similarly, it has been
shown that several homoeotic mutations in Drosophila
can cause the same morphological transformation
(Lewis 1968 ; Garcia-Bellido 1977).
Teratologies are very often caused by genetic
mutations, but the explanation of the resultant patterns
of morphological organization has to be searched for
at the developmental level.
a. Brief historical o v e r v i e w
Unlike evolutionary classifications based on
lineage relationships, teratologies have traditionally
been understood and classified on the basis of deve-
lopmental properties (Zwilling 1955). One of the ear-
liest semi-scientific classifications of teratologies was
put forth by the French surgeon Ambroise Pard in his
colorful and, like most bestiaries of its kind, bizarre
treatise "Monstres et Merveilles", first published in
1573. Pard's classification of teratologies was, in part,
based on rudimentary notions of the mechanisms that
control development. To Pard, normal development
was the result of mixing the correct amounts of male
and female " s e e d " . A class of monsters would result
from failure to mix adequate amounts of the two ingre-
dients. Thus, one could obtain monsters resulting from
" t o o great a quantity of seed", which would cause the
formation of extra structures (e.g. conjointed twins or
extra limbs), or, alternatively, abnormalities could be
generated by "lack in the quantity of seed" (e.g. cyclo-
pia or limblessness). Another category of monsters -
consistent with his scheme and beliefs of the time -
would be the ones resulting f r o m mixture or mingling
of seed from different species. Interspecific hybridiza-
tion was commonly accepted to occur at the time and
the literature is full of examples of half h u m a n / half
beast creatures having been born out of bestial sexual
relations. Pard had numerous other categories ranging
from plausible mechanical constraints in the womb to
hermaphrodites to examples of the wrath and glory of
God. I do not want to enter into the details of Pard's
classification (see Pallister 1982, for further informa-
tion on Pard and his work), except to illustrate one of
the earliest examples of how a specific model of deve-
lopment was used to construct a classification of tera-
tological form.
A much more sophisticated, and scientific, classi-
fication of teratologies is offered in the treatise by Isi-
dore Geoffroy St. Hilaire, already mentioned in the pre-
vious section. I. Geoffroy's classification draws exten-
sively f r o m the theories of his father Etienne and his
father's disciple, the medical anatomist Etienne Serres.
These authors belonged to the school of French Trans-
cendental morphology (Russell 1916), closely associa-
ted with German Naturphilosophie. French transcen-
dentalists shared a set of assumptions with their Ger-
man colleagues. They included the belief that all ani-
mals are built upon a single structural plan, the idea
of a "chain of being" (the Aristotelian concept that
all animals can be arranged in a single graded scala
naturae according to their degree of perfection, as mea-
sured by their structural complexity, see Lovejoy 1936)
and a belief in recapitulation (the concept that argues
that animals, as they develop, go through a series of
embryonic stages that parallel the chain of being).
One of the most successful applications of the
theories of recapitulation was in the analysis of tera-
tologies (Gould 1977 ; p. 49-52). To the French trans-
cendentalists, as well as to the Naturphilosophers such
as Oken, Meckel, and to their descendants, the Haec-
kelians, the ordered generation of teratologies was the
result of regulation within an invariant ontogenetic
 -- 34 --

No

4ol 1 4b

5b

6o

9a ~ 9b
Fig. 7 - - Dorsal and lateral views of guinea pig skulls.
Normal (Na, Nb) and various degrees of head reduction, cyclopia and otocephaly (1 to 9) (from Wright & Wagner 1925). Drawing
arranged in increasing degree of reduction of head structures. Usually the lower jaw is the first to be shortened (1-2). In some cases,
however, the upper jaw is affected (1'). This latter stage probably should not be part of the otocephaly series.
Vues dorsale et lat~rales de cranes de cochons d'Inde.
Normal (Na, Nb) et diff6rents degr6s de r6duction de la t~te, cyclopie et otoc6phalie (1 b. 9) (d'apr~s Wright & Wagner 1925). Dessins
ordonn6s par ordre croissant de r6duction des structures de la t&e. Habituellement la mandibule est raccourcie en premier 0-2).
Dans certains cas cependant la mfichoire sup~rieure est affect6e (1'). Ce dernier stade n'existe probablement pas dans la s6rie
otoc6phalique.
 m 35 m
sequence (reflected in the scale of being). For exam-
ple, Oken emphasized the relationships between tera-
tological and foetal structure, and affirmed that " m a l -
formations are only persistent foetal conditions" (cited
in Russel 1916, p. 91). In a similar vein, I. G e o f f r o y
discusses the parallelism of the "serie zoologique" with
the "serie teratologique". He argues that teratologi-
cal anomalies in advanced species reproduce the con-
ditions normally found in " l o w e r " species. As in the
case of some of the analyses of Par6, we are dealing
with a system of classification of f o r m rooted on the
developmentalist concepts of the time.
Gould (1977) discusses a celebrated example of this
type of interpretation of teratologies on the basis of
recapitulation. Serres, through a detailed comparative
anatomical study claimed to have demonstrated that
a headless (anencephalic) human fetus was a condition
generated through an arrest of development. In this
particular case, Serres argued that the embryo had stop-
ped developing at a stage in the "scale of being" homo-
logous to a mollusk.
A very influencial dichotomy drawn by I.G. St.
Hilaire was that distinguishing between monsters by
excess and monsters by default. The latter simply reflec-
ted conditions found in lower forms. The former,
however, did not result in an extension of the scale of
being into new designs. Instead, monsters by excess
always resulted in duplication of existing structures.
The recapitulatory ideas of early teratologists were
abandoned, even if their particular taxonomy has often
been retained, by studies based on more dynamical
models of development and pattern formation. Uni-
versal rules need to be replaced by system-specific inter-
pretations, as illustrated in the next section.
b. A d e v e l o p m e n t a l analysis o f head reduction and o f
c o n j o i n e d twins : a c o n t e m p o r a r y classification o f
monsters
The observed regularities in the generation of tera-
tological form can be explained in terms of morpho-
genetic properties. I will illustrate this point by exami-
ning two specific teratological systems: the trend
towards increasing loss of head structures and the gene-
ration of conjoined twins.
My choice of these two seemingly unrelated clas-
ses of teratologies is not an arbitrary one. Several clas-
sical authors had already pointed out that they may
reflect a single developmental trend (e.g. Wilder 1908
Fig. 8 -- "Cosmobiotic series" from cyclopia to axial duplication
from Wilder (1908).
Wilder defined Cosmobia as the set of all possible forms
that could be generated by continuous regulation in rates
of development.
"S6rie eosmobiotique" depuis un stade cyclopejusqu'~ une
duplication axiale d'apr6s Wilder (1908).
Wilder d6finit la "s6rie cosmobiotique" comme l'ensem-
ble de toutes les formes possibles qui pouvaient ~tre pro-
duites par une r6gulation continue des taux de
d6veloppement.
 - -
and Stockard 1921, fig. 8). These authors believed, on
the basis of comparative analysis and experimental per-
turbation, that the headlessness otocephaly cyclopia
normal axial duplication sequence was the result of
quantitative regulation of some underlying develop-
mental process. Stockard (1921) specifically proposed
a slowdown in the rate of development at various
embryonic stages as the single cause of this sequence
of form transformations. That a mechanistic relations-
hip exists among these teratological conditions is sup-
ported by the recent research of Gerhart and collea-
gues (Gerhart et alii 1986) who have convincingly shown
that both reduction and duplication of head structu-
res can be generated by alterations of the process of
cytoplasmic compartmentalization in the early cleavage
stages. This perturbation in early development results
in changes in the patterns of mesodermal-ectodermal
interactions that characterize the establisment of the
body axis.
For example, cyclopia and related conditions
shown in figure 7, can be explained in terms of a quan-
titative perturbation of a single developmental para-
meter : rate of mesodermal migration during gastru-
lation. This migration rate in turn determines the
amount of head mesoderm at the time of induction of
head structures (Adelmann 1936 ; Juriloff et alii 1985).
Thus, a quantitative perturbation in a single parame-
ter triggers an ordered series of qualitatively different
morphological states.
The point to emphasize here is not the specific
mechanisms controlling a particular process but the fact
that although the final morphological transformation
is highly invariant, the relationship between it and the
initial developmental perturbation is extremely com-
plex. For example, let us assume that a mutation affects
the rate of polymerization of tubulin molecules into
microtubules. This genetically mediated quantitative
change in the rate of microtubule assembly will affect
the rate of cytoplasmic rearrangement that follows the
fertilization of the egg (Vincent et alii 1986). This
change in the redistribution of cytoplasmic components
will not have an effect until the time of gastrulation.
At gastrulation, changes in the cytoplasmic make-up
of invaginating, anteriorly migrating, mesodermal cells
will cause a reduction in the amount of head mesoderm
(Suzuki et alii 1984 ; Gerhart et alii 1986). A smaller
population of head mesoderm cells will trigger a series
of abnormal inductive events in the overlying ectoder-
mal neural plate (Adelmann 1936), as well as changes
in the number of neural crest cells, which can have a
wide range of secondary effects in the region (Noden
1986).
However, as already noted by Wright & Wagner
(1925), the final morphology is not only the result of
these fundamental changes in gastrulation and primary
36 - -
induction. The observed sequence of changes in mor-
phology (fig. 7) is the result of a combination of pri-
mary effects, such as lack of inductive events, and a
series of correlated changes in the patterns of growth
and differentiation. For example, the loss of certain
cranial bones, such as the alisphenoids and palatines
could be interpreted as being correlated with a shorte-
ning of the mandibular arch (which is the result of a
slow down in the rate of migration of neural crest cells
into the region). These feedback interactions between
the central nervous system, sensory organs, chondro-
cranium and dermatocranium have been well demons-
trated experimentally (e.g. see reviews by Murray 1936 ;
Katz 1983).
The results of Wright & Wagner (1925) illustrate
the highly dynamic and interactive nature of the deve-
lopmental system. As they conclude (p. 439) : " T h e
case illustrates the extent to which morphological chan-
ges of an apparently qualitative sort may be brought
about as a result of ramifying correlative effects from
initial gene effects of a simple quantitative s o r t " .
Hyperdevelopment of anterior structures as well
as axial duplication can also be caused by changes in
the patterns of cytoplasmic compartmentalization
during early development (Black & Gerhart 1986). We
must distinguish this mechanism from other ways of
generating conjoined twins. In fact, a classification of
double monsters should be based on such mechanistic
knowledge. Many early authors, such as I. G e o f f r o y
St. Hilaire (1836) or Stockard (1921) assumed that the
only way to make a double monsters was by the fusion
(or failure to completely separate) of monozygotic
twins. A review of the literature suggests that there are
probably several different ways to generate a mamma-
lian conjoined twin. The three varieties of incomple-
tely separated twins appear to be manifestations of dif-
ferent processes operating at different stages of deve-
lopment. The first class in composed of cases in which
the inner cell mass fails to completely separate after an
initial fission (Hsu & Gonda 1980). Another possibi-
lity is a secondary fusion of twin blastocysts. In these
two cases, the double embryo may be joined at any
region, the two parts will not be symmetrical (this is
probably the causal mechanism of the so-called para-
sitic twin teratology illustrated in figures 6c and 6f),
and two amniotic cavities will be present. The speci-
mens illustrated in figures 6b and 6e have most likely
resulted from incomplete division of the early blastula
stage. The third class of double monsters are the ones
resulting from a bifurcation of the primitive streak
(Herring & Rowlatt 1981 ; Partlow et alii 1981 ; Eas-
ton 1985). This class of teratologies can be diagnosed
in mammals on the basis of the presence of a shared
single amniotic cavity, and the presence of a single axis
that branches anteriorly into two axes resulting in
 m 37
symmetrical anterior structures (fig. 6a and 6b). Black
& Gerhart's (1986) centrifugation experiments of X e n o -
p u s eggs also result in conjoined twins with a bifurca-
ted body axis (see also Kunieda & Wakahara 1987).
A developmental analysis of this sort is not only
useful to classify teratological forms but would even-
tually allow us to predict which morphologies are easier
to generate. For exaniple, the pattern formation models
discussed by Oster & Alberch (1982) and Oster et alii
(1988) suggest that a smooth perturbation of a given
C. A D E V E L O P M E N T A L A P P R O A C H TO T H E ANALYSIS OF E V O L U T I O N A R Y PATTERNS -
T H E A D A P T I V E R A D I A T I O N OF T H E VERTEBRATE LIMB
Limb diversity in tetrapods is a classic example of
~,,~vtive diversification within a conserved body plan.
Consider the widely divergent functions and drastically
different external shapes of the wing of a bat, the leg
of a horse and the fin of the whale. In spite of these
differences, all tetrapod limbs share a similar skeletal
arrangement. The vertebrate limb is usually divided into
a proximal segment or stylopodium (always composed
of one bone, the humerus in the forelimb and the femur
in the hindlimb), followed by one containing two bones,
the zeugopodium (radius-ulna ; tibia-fibula), which, in
turn, is connected to the distalmost segment, the auto-
podium, including a set of wrist bones followed by
digits. It is astonishing that this morphological plan has
been conserved for millions of years of evolutionary
history even in the face of divergent selective pressures.
The vertebrate limb played an important role in
the elaboration of transcendentalist (i.e., internalist)
ideas. It was a key example to illustrate the ideas of
early pre-evolutionist German natural philosophers
such as Oken and Goethe and subsequently adopted
by such classical morphologists as Owen and Gegen-
bauer. The limb with its metameric organization and
conserved pattern of connections among skeletal ele-
ments was a perfect example of serial repetition of parts
within an invariant body plan ; a much more unambi-
guous example of the postulates of the Naturphiloso-
phie School than the widely cited but more controver-
sial claims about the segmental organization of the ver-
tebrate head proposed by the same authors.
The externalist explanation of this pattern has been
that limbs share a common structural plan because they
are all derived from a common ancestor. Most aspects
of this plan have not been changed by selection because
is hat not been necessary.
In this section, i briefly summarize recent work
that addresses this problem from a renewed internalist
perspective. Such an approach requires the integration
of mathematical modeling (Oster et alii 1985 and 1988),
- -
developmental parameter (e.g. number of mesodermal
cells in the head region) above a certain threshold can
trigger a bifurcation of an anteriorly growing axis. Con-
versely, a trifurcation is extermely unliked ; an unsta-
ble pattern requiring a very delicate choice of parame-
ter values. One may speculate that the rarity of triple
monsters, discussed by Meckel and I. Geoffroy St.
Hilaire, may be a reflection of the inherent difficulty
of causing a trifurcation of the anteriorly advancing
primitive streak or archenteron during gastrulation.
comparative analysis (Alberch & Gale 1985 ; Shubin
& Alberch 1986) and experimental manipulation of
development (Alberch & Gale 1983 and unpublished).
The basic hypothesis is that "rules of construction"
determine not only how a limb is built during ontogeny
but also how it can be modified through phylogeny.
It is the nature of these developmental properties which
is responsible for the observed invariances in the evo-
lutionary diversification of tetrepod appendages.
Based on empirical observations, Shubin &
Alberch (1986) proposed that limb skeletal patterning
should not be viewed as the global specification of inde-
pendant cartilage foci. Instead, the skeletal pattern of
the limb results from an initially continuous cartilagi-
nous condensation that grows anteriorly, and sequen-
tially branches and segments to give rise to discrete ele-
ments. A single proximal element (femur/humerus)
begins to grow distally and subsequently branches into
two elements (tibia/fibula ; radius/ulna). Then, a more
complex pattern of branching events is responsible for
the genesis of the carpus/tarsus and digits. Individual
skeletal elements form by the splitting ("fission") of
an initially continuous cartilaginous rod (fig. 9). The
observations of Shubin & Alberch (1986) support a
model of pattern specification in which local pattern
emerges as the result of local morphogenetic interac-
tions ; they are consistent with the mathematical models
of pattern formation proposed by Oster et alii (1985)
and Oster et alii (1988). In fact, mathematical mode-
ling, comparative analysis and experimental perturba-
tions suggest that all limbs are constructed as variations
in the iteration of three basic types of cartilage con-
densation. A cartilage element can form de n o v o as an
independant foci. It can branch and split into two ele-
ments ( " b " event in figures 9 and 10) or, alternatively,
a continuous rod of cartilage can segment into two or
more elements (denoted as " s " events in figures 9 and
10). For example, figure 10a illustrates, superimposed
on a fully developped limb, the sequence of branching
and segmentation events that give rise to the skeleton
 - - 38 - -

A d

~5

13

Fig. 9 (A) Low-power and (B) high-power photomicrographs showing the embryonic connections in the developing carpus of a larval Ambys-
toma which has been cleared and the chondrocytes stained with Alcian Blue.
(B) Illustrates the branching event ( " B " ) that produces the ulnare (u) and intermedium (i) and the segmentation event ( " S " ) that
produces the radiale (r) from the radius (R). In the low-power view (A), the overall pattern is seen. Notice the segmentation events
that produce the radiale (r) from the radius (R), element (y) from the radiale (r), and the centrale (c) from the intermedium (i).

Microphotographies ~ faible grossissement (A) et h fort grossissement (B) montrant les connections embryonnaires dans les carpes
en d~veloppement de larves d'Ambystoma qui ont ~t~ ~claircies et dont les chondrocytes ont ~t~ color,s au Bleu d'Alcine.
(B) montre l'6v6nement de bifurcation ( " B " ) qui donne l'ulnare (u) et l'intermedium (i), et l'6v6nement de segmentation ( " S " )
qui donne la radiale (r) ~t partir du radius (R). La rue ~ faible grossissement (A) donne le sch6ma d'ensemhle. A noter les 6v6nements
de segmentations qui donnent la radiale (r) ~t partir du radius (R), l'616ment (y) ~ partir de la radiale (r) et la centrale (c) ~ partir
de l'intermedium (i).
 --
of the generalized five-toed, limb of the salamender
A m b y s t o m a mexicanum.
Experimental manipulation of normal limb deve-
lopment with colchicine, and other mitotic inhibitors
with reversible effects, can generate a variety of abnor-
mal morphologies (Alberch & Gale, 1983, 1985;
Alberch, in prep.). Alberch & Gale (1983) have argued
that changes in pattern formation occur as the domain
of the early embryonic field (the size and number of
cells of the limb bud) is reduced below a certain thres-
hold - a hypothesis consistent with mathematical
models of pattern formation (e.g. Oster et alii 1988).
The important point is that the malformations indu-
ced by the colchicine treatment are not chaotic ; to the
contrary, there is a high degree of order. As discussed
in previous sections, the ordered generation of terato-
logies is one of the fundamental properties of the mor-
phological systems. Figure 10b-c illustrate two stages
in the series towards increasing reduction of digits and
skeletal elements induced by colchicine treatment. This
is a true "cosmobiotic series" (fig. 8), in the sense that
the realm o f morphologies obtained through experi-
mental manipulation is the result of perturbation of one
or more underlying developmental parameters. The
property o f transpecific parallelism is also illustrated
in this example. For example, the teratologies illustra-
ted in figures 10b-c correspond, to a striking degree of
similarity, to morphologies found in derived urodele
species (figures 10d-e).
This transpecific parallelism can be explained in
terms of the experimental perturbation affecting the
sequence of branching and segmentation chrondroge-
nic events. For example, the cave-dwelling salamander
Proteus anguinus (fig. 10e) represents a highly derived
limb morphology characterized by an extreme case of
loss of tarsal elements and digits. As illustrated by the
parallel between Figures 10c and 10e, the morphology
of Proteus is the result of a reduction in the number of
chondrogenic segmentation events as well as the switch
from a branching to a segmentation event off the fibula.
Not all laboratory induced malformations result
in forms observed in nature. But even these " u n n a t u -
ral" constructions, are limited by the morphogenetic
properties of the system. For example, Patou (1973)
removed and disaggregated the mesoderm from chick
and duck limb buds. The two cell populations were
mixed, reaggregated and packed into an ectodermal jac-
ket. As expected, this procedure resulted in highly a-
bnormal, and'non-functional, skeletal patterns (fig. 12).
D. TOWARDS A T H E O R Y OF FORM
Evolutionary biology needs a theory of form. Cur-
rent neo-Darwinian theory is essentially a blend of Men-
delian genetics and a populational theory of natural se-
lection. The organism is viewed as a black box, passively
39 --
Nevertheless, close observation of these morphologies
indicates that they are built as interactions of the three
basic types of cartilage condensation patterns shown in
fig. 9.
Shubin & Alberch (1986) have suggested that these
basic morphogenetic rules for skeletal differentiation
have remained invariant throughout vertebrate history.
That is, all vertebrate limbs result from a combination
of de novo, branching and segmentation events. Besi-
des these local morphogenetic interactions, globally
specific asymmetries are also critical in controlling limb
patterning. Such " g l o b a l " properties are basically the
result of groups of specialized cells exerting long range
influences on the vertebrate field (e.g. the apical ecto-
dermal ridge or the zone of polarizing activity ; see
Hinchliffe & Johson 1980 for review). The evolution
of limb diversity is the result both of changes in cellu-
lar morphogenetic properties that either affect local
interactions, such as cell adhesiveness or extracellular
matrix constitution, or global parameters, such as the
slope of a gradient o f morphogen concentration. In
both cases a perturbation in cellular parameters can
result in alterations in the sequence of branching and
segmentation events. For example, salamanders appear
to develop their limbs in ways quite different from other
teti:apods (see reviews in Shubin & Alberch 1986 and
in press). In particular, the sequence of digit f o r m a -
tion appears to be reversed (e.g. Alberch & Gale 1983).
Alberch & Gale (1985) documented a parallel between
the experimentally generated patterns and the phylo-
genetic trends towards digital reduction observed in
frogs and salamanders. Reduction of digits, a pheno-
menon that has occurred independently several times
in the evolution of amphibians, entails the loss of the
innermost (preaxial) digit in frogs, but the outermost
(postaxiat) one in salamanders. When a generalized sala-
mander limb bud was treated with a mitotic inhibitor
a postaxial digit was often lost. If the same experiment
was performed on a frog, the first digit was lost (fig. 11).
This parallel between phylogenetic trends and
experimental results (coupled with the observed diffe-
rences in the ontogenies of frog and salamander limbs
(Shubin & Alberch 1986) suggests that the developmen-
tal differences that have evolved in these groups deter-
mine the variations that can arise and become fixed
during evolution. In reference to Appendix II (fig. 19
one would say that the frog and salamander limb-
patterning systems have different evolutionary poten-
tials, in terms of the variation that each can generate.
responding to externally determined selective pressures.
The concepts of regulation and feedback that characte-
rize developmental systems are conspicuously absent
from existing theoretical schemes (Wake et alii 1983).
 n 4 0 m

Fig. 10 - - A. Normal foot morpho-

logy of the salamander
Ambystoma mexicanum.
Treatment of the embryo-
nic limb bud of A. mexi-
canum with the mitotic
inhibitor colchicine results
in the formation of terato-
logical limbs with fewer
skeletal elements (e.g.
v',,_ ],
four-toed (B) or two-toed
limbs (C). This array of
morphologies could be vie-
wed as a "cosmobiotic
series" (see fig. 8). The
pattern of experimental
variation is not r a n d o m
and the teratological forms
obtained often correspond
to the normal morpholo-
gies observed in evolutio-
narily derived species of
urodeles, such as the four-
toed, Hemidactylium scu-
tatum (D) and the two
toed, Proteus anguinus
(E). Dotted lines indicate
the pattern and types of ,
cartilage connections
during development, s =
I ~ $
segmentation of a cartilage
rod, b = branching of a
chondrogenetic foci (see
fig. 9). Loss of elements in
the developmentally per-
turbed or evolutionary
derived species are usually
the result of failure of the
-

embryonic chondrogenetic
foci to split ( " s e g m e n t " )
into two. The failure o f a
s e g m e n t a t i o n event to
occur is denoted by an
asterisk (from Alberch &
Gale 1985 and unpublished
data).

A. Morphologie normale de
la patte ehez la salamandre
Ambystoma mexicanum.
Traitement du bourgeon
de membre embryonnaire
de A. mexicanum avec un
inhibiteur mitotique (col-
chicine) qui aboutit A des
m e m b r e s t6ratologiques
poss~dant moins d'~l&
ments squelettiques :
membres ~ qnatre orteils
(B) ou ~t deux orteils (C).
!S ) 7,"1
:*-J-!~~oteus
Cette succession de mor-
phologies peut ~tre com-
prise c o m m e une "s6rie
cosmobiotique" (cf. fig.
8). Le mod61e des varia-
tions exp6rimentales n'est
pas al~atoires et les formes F T
t6ratologiques r6alis6es g T
correspondent souvent
des morphologies normales
rencontr6es dans des esp6ces parentes d'urodbles c o m m e l'Hemidactylium scutatum A quatre orteils (D) et le Proteus anguinus
deux orteils (E). Les lignes pointill6es indiquent les modes et les types de connections cartilagineuses pendant le d6veloppement.
s = segmentation d ' u n e barquette cartilagineuse, b = bifurcation chondrog6n6tique (cf. fig. 9). La perte des 616ments par pertur-
bation exp6rimentale du d6veloppement c o m m e par 6volution naturelle r6sulte d ' u n e incapacit6 & se diviser en deux des points
chondrog6n6tiques embryonnaires. L'absence d'6v6nement de segmentation est signal6e par une ast6risque (d'apr6s Alberch & Gale
1985 et donn6es in6dites).
 --41 --

III IV Fig. 11 - - An experimental approach

to the study of phyiogene-
SALAMANDERS (7) tic trends.
FROGS (2)
A. Two anuran lineages
have lost toes indepen-
dently during phylogeny.
In both cases the first toe
("the t h u m b " ) is the one
that has been lost. In sala-
manders digital loss has
occurred in at least seven

I independant cases during

evolution. In all of the ins-
tances the forms have con-
verged in the loss of the
fifth toe. B. Identical treat-
A. Evolutionary trends ment of an embryonic limb
bud with a mitotic inhibi-
tor with reversible effects
results in the loss of pre-
axial digits in frogs while
Ill IV salamanders lose post-axial
elements. These differences

FROGS
\l//
80g
in experimentally generated
forms parallel observed
evolutionary trends (from
Alberch & Gale 1985).

Approche exp~rimentale de

0
III IV
[[ I'~tude des tendances
phylog~n~tiques.
A. Deux lignGes d'anoures
..I
0
-r-
eL
e~
0
IE
I ont perdu leurs orteils indd-
pendamment au cours de la
phylogenGse. Dans les deux
cas le premier orteil (le
pouce) est celui qui a ~t6
ml perdu. Chez les salaman-
<1
ev
I'--
LLI
TIBIA /I I,
i FIBULA
III IV
dres la rdduction digitale
s'est produite dans au
moins sept cas indGpen-
dants au cours de l'6volu-
7 tion. Oans tousles cas c'est
le cinquibme orteil qui a 6t6
perdu. B. Le m~me traite-
ment d ' u n bourgeon de

SALAMANDERS
[[ membre embryonnaire par
un inhibiteur mitotique /t
effets rGversibles aboutit ~t
la perte du doigt prG-axial

I chez les grenouilles et ~ la

perte des 616ments post-
axiaux chez les salaman-
dres. Ces diffdrences entre
les formes gdndrGes expdri-
mentalement sont similaires
[3. Experimentally generated morphologies aux tendances 6volutives
observ~es.

In this section, I will define the concept of form, racterize development rather than on specific genetic
not as a static entity but rather as a process. My final constitution.
conclusion is that a theory of form must be based on
the properties of the network of interactions that cha-
 - - 4 2 - -

1. W H A T IS F O R M ? Form embodies all the relations of the organism and

The developmental biologist Weiss (1955) equated
organic form with frozen development. With this sta-
tement, Weiss meant that form cannot be dissociated
from process. Form is not a static entity defined by the
spatial position of components, but a dynamic process.
expresses the whole and its internal organizing proper-
ties. This definition, rooted is the Romantic ideas o f
Goethe, represents a tradition now absent from evolu-
tionary biology (Lenoir 1984 ; Brady 1984 ; Webster
& Goodwin 1982). It stresses the concepts of interac-
tion, integration and regulation. To understand form

Fig. 1 2 - Various patterns produced

by Patou's disaggregation-
reaggregation experiments.
Notice that in each case the
final pattern is produced by
a combination of brala-
ching and segmentation
events (from Hinchliffe A
1977).

Diff6rents motifs obtenus

dans les exp6riences de
d6sagr6gation-r6agr6gation
de Paton.
On remarque que dans cha-
que cas le motif final est
obtenu par une c o m b i n a
son d'6v6nements de bi:fu
cation et de segmematic
(d'apr6s Hinchliffe 1977

[3
 -- 43 --

and its rules of transformation we need to know the
properties and nature of its generative rules. These rules
encompass genes, development and function in a man-
ner that cannot be dissociated.
2. GENERATIVE RULES -
THE MAPPING OF GENES TO PHENOTYPE
There are two ways to conceptualize the relation-
ships between genes, development and phenotype (fig.
13). Since the discovery of genes as the units of here-
dity, the?e has been a tendency to view genes as the
determinants of form. Genes control developmental
processes, which in turn, generate f o r m (fig, 13a). If
this hierarchical scheme were correct, both morpholo-
gical evolution and development could be reduced to
purely genetic problems. This is reflected in the posi-
tion of some Mendelian geneticists who view evolution
as a change in gene frequencies, or, in the molecular
biologist's view of development, as a temporal and spa-
tial sequence of gene expression.
This depiction of genes and development as inde-
pendent levels is incorrect in the sense that genes do
not specify development, or even form, because gene
action itself is intimately linked to developmental inte-
ractions. This interactive nature of developmental pro-
cesses is illustrated in fig. 13b. Genes make proteins
that either regulate the expression of other genes, or,
in the case of products o f the so-called morphogenetic
genes (e.g. Edelman 1985 ; 1986a, b), determine mor-
phogenetic properties such as extracellular matrix com-
position, cell adhesion, mitotic rate, diffusion constant,
kinetic activity, etc. Morphogenesis is the result of com-
plex physico-chemical interactions at this level. One of
the outcomes of morphogenetic processes is that the
spatial relationships a m o n g cell populations are alte-
red. Often, a so-called inductive event occurs when
populations of cells with different developmental his-
tories are suddenly juxtaposed as a result of a morphoge-
netic process. Induction implies that the expression of
some genes is repressed while a new set is turned " o n " .
The implications of this cyclical/feedback scheme
drastically alter our perception of how complex mor-
phologies evolve. Development cannot be reduced to
a problem of gone expression, since gone expression
itself is under epigenetic control. Therefore, although
gone frequencies are a valid method for evolutionary
" b o o k k e e p i n g " (see Wimsatt 1980 ; Sober & Lewon-
tin 1982), we cannot have a purely genetic theory of
morphological evolution. Theory of f o r m has to be
based on the global properties of the network of inte-
ractions that characterize development (fig. 13b ; see
appendices I and II).

A B
MOP"OLOGY I /
l- G \
\
\
\

CELL morphogenesiI sTISSUE

\

~,
PROPERTIES GEOMETRY t1
I
I
L)EVELOPMENTAL protein l induction / ; 1
PARAMETERS synthesis~
/
/
/
\
\
--f GENES ~-- 1
/

i/" / "" "" X\l

GE.ES [ ,, gene /
I
\\ regulation / /.

Fig. 13 - - A. Hierarchical scheme of the genesis of form with genes as the controlling agents. B. Cyclical view of development in w h i c h genes
are j u s t one step in the c h a i n o f interactions. D o t t e d lines i n d i c a t e the two k i n d s of r e g u l a t o r y l o o p s discussed in the text. 1 - cell
a u t o n o m o u s ; 2 - epigenetic.
A . Schema hi~rarchique de ia gen~se de la forme 06 los g~nes agissent comme agents de contr61e. B. Vue cyclique du d~veloppement
d a n s lequel los g~nes sont une s i m p l e ~tape d a n s une cha~ne d ' i n t e r a c t i o n s . Los lignes pointill~es i n d i q u e n t los deux types de r6gula-
t i o n discut~s dans le texte. 1 - a u t o n o m i e cellulaire ; 2 - ~pigen6se.
 --
This feedback relationship can be extended to the
level of interactions between form and function. The
form/function dichotomy is one of the oldest problems
of morphology, certainly since the Cuvier and Etienne
Geoffroy Saint-Hilaire debates (Russell 1916 ; Appel
1987). Again, the relationship was viewed as a hierar-
chical one with either form determining function or vice
versa. I believe, however, that later stages in develop-
ment could be characterized as a dialogue between form
and function. For example, the movement of embryos
inside the egg or the mother's womb may be more than
a spurious epiphenomenon. Movement is a requirement
for adequate integration of the nervous, muscular and
skeletal system [for specific references on the effects
of movement on joint formation and bone shape see
Drachman & Sokoloff (1966), Hall (1969), Lanyon &
Rubin (1984) ; for the effects of function on the deve-
lopment of the nervous system see Katz & Lasek (1978),
Katz et alii (1981) ; and for a general discussion on the
evolutionary implications of this form - function feed-
back see Alberch (1982) and Katz (1983) for general
reviews and Meyer (1987) for recent experimental
work]. Therefore, it is impossible to state that form
determines function or vice versa since they are inter-
connected at the level of generative process.
3. M O R P H O G E N E T I C RULES VS. M O R P H O L O G I C A L PAT-
TERNS : THE NATURE OF REGULATORY INTERACTIONS
In previous sections I have demonstrated that cer-
tain patterns of morphological organization avxt trans-
formation remain constant through long periods of
evolutionary time. The existence of order in the for-
mation of teratological form (section B. 1), or the evi-
dence in support of developmental rules of organiza-
tion and evolution in the vertebrate limb (section C)
are examples of such phenomena. These regularities in
morphological pattern suggest a high degree of inva-
riance in the structure of the developmental processes
schematically illustrated in figure 13b. In this section
I briefly review some empirical evidence in support of
this hypothesis. In particular, my basic thesis is that,
.if the structure of developmental interactions is highly
conserved in evolution, there should be a finite num-
ber of generative processes. Morphological diversity is
the result of the repeated iteration of the same rules
in different contexts.
Developmental interactions are mediated by gene
products. There are two distinct pathways through
which genes can regulate developmental processes. I
refer to these regulatory pathways as "intracellular"
and "epigenetic" (fig. 13b). The intracellular regula-
tory pathway is characterized by genes that directly con-
trol the expression of other genes - the products of such
"regulatory" genes never exiting the cell. An epigene-
tic pathway is one in which gene products are trans-
ported to the cell surface or the extracellular matrix.
44 --
In this case, developmental regulation is the result of
complex physico-chemical interactions that determine
cell behavior and extracellular matrix composition. In
turn, morphogenetic interactions result in the expres-
sion of heterogenous spatial patterns among groups of
cells - a prerequisite for inductive events.
a. Gene regulation
Control of cell autonomous development, such as
the expression of homoeotic genes in Drosophila (Stern
1954) or trans-determination behavior (fig. 4a), is
mediated by intracellular networks of genetic interac-
tion. The process of insect segmentation is one o f the
best understood examples of such type of developmen-
tal regulation.
Extensive genetic analysis in Drosophila has revea-
led that two classes of genes expressed in the zygotic
genome are responsible for the formation of the seg-
mented pattern characteristic of all insects. "Segmen-
tation genes" are necessary to establish the correct seg-
ment number and polarity (Nusslein-Volhard & Wies-
chaus 1980 ; Hiromi et alii 1986). This first step in the
process of specification of segment number is media-
ted by a complex set of interactions between the pro-
ducts o f " segmentation genes" and maternally inheri-
ted cytoplasmic determinants (e.g. Hiromi et alii 1985 ;
see Meinhardt's model discussed in Appendix I). This
process results in a spatially banded pattern of gene
expression. The resultant banded pattern is not enco-
ded in any of the segmentation genes ; it emerges as
the result of the interactions among the products of the
various genes involved in segmentation and the mater-
nally inherited cytoplasmic determinants.
While segmentation genes specify the number of
metameric units, homoeotic genes are required to assign
the proper identity to each segment (Lewis 1978;
Garcia-Bellido 1986 ; Seeger & Kaufman 1987). Analy-
sis of double mutants suggests that the establishment
of segment number (an "epigenetic" regulatory path-
way) is independent of the process of specification of
the differences among segments (a "cell autonomous"
pathway).
Homoeotic genes are one of the best examples of
an "intracellular" regulatory pathway (indicated as 1
in fig. 13b). These genes appear to directly control the
expression of a series of "morphogenetic genes" (i.e.,
genes that mediate development via the "epigenetic path-
way" by regulating developmental properties such as cell
adhesion, cell motility, reaction rates of diffusible mor-
phogens, composition of the extra-cellular matrix, etc.).
Garcia-Bellido (1986) refers to the homoeotic genes as
"selectors" and suggests that a particular developmen-
tal pathway is genetically specified by a combination of
selector genes in the " o n " or " o f f " condition. Unlike
the highly specific "selector" genes, morphogenetic
 --45 --
genes (equivalent to Garcia-Bellido's " r e a l i z a t o r "
genes) are general in their expression. That is, they
mediate a wide variety of morphogenetic and induc-
tive processes (see below).
Garcia-Bellido (1983 and 1986) has argued, based
on available data on the roles of segmentation and
homoeotic genes, that the discreteness of the phenoty-
pic space discussed in fig. 1 is a direct reflection of the
possible genomic combinations of selector genes. That
is, since he believes that few genes control the selec-
tion of alternative major developmental pathways (e.g.
decision to f o r m a leg a n d / o r antenna) and that each
selector gene can only exhibit two states, " o n " or
" o f f " , there is a finite number of possible developmen-
tal pathways. This number is determined by all possi-
ble combinations of genomic states, each combination
corresponding to a specific class of phenotypes.
Although radical - and, at least for vertebrates,
most likely incomplete - Garcia-Bellido's hypothesis is
very relevant in the sense that it emphasizes an inter-
nalist approach to morphological evolution. In addi-
tion, he documents a fact critical to my argument : that
there is a finite number of genetic " o p e r a t i o n s " at the
level of intracellular regulation.
b. Epigenetic regulation of morphogenesis and
pattern formation
It is simplistic to view development as a simple
sequence of gene control switches. Even the models of
cell autonomous regulation cited above have an "epi-
genetic" component in the form of gradients or waves
of morphogens (e.g. Garcia-Bellido 1977 ; K a u f f m a n
1977; Meinhardt 1984; Ingham & Martinez-Arias
1986). Morphological pattern results from the interac-
tion between intracellular networks of gene regulation
and extracellular (epigenetic) morphogenetic interac-
tions. Whatever order emerges f r o m the structure of
networks of intracellular gene regulation is enhanced
by the existence of a recurrent and finite set of rules
of interaction that characterize the epigenetic regula-
tory. This view is supported by available data sugges-
ting that processes of organogenesis and pattern for-
mation are mediated by a relatively small number of
molecules acting in a wide variety of contexts.
This point has been elegantly illustrated by the
work of Edelman and colleagues on cell adhesion mole-
cules (CAMs) (Edelman 1985 ; 1986a, b), as well as
with the work on a few other morphogenetic molecu-
les such as fibronectin (Thiery et alii 1985) and cyto-
tactin (Grumet et alii 1985 ; Crossin et alii 1986 ; Mac-
kie et alii 1987). This conceptual framework argues that
there are few genes that mediate morphogenetic and
inductive events.
So far I have argued for a limited set of gene con-
trol operations and for a finite number of morphoge-
netic molecules. This analysis of developmental rules
can be extended to more phenomenological levels such
as cell behavior and patterns of tissue induction. Wes-
sels (1982) convincingly reviewed the existence of a very
reduced set of morphogenetic cell behaviors (e.g. cell
shape change, chemotaxis, haptotaxis, etc.) that are
repeatedly used in different processes of organogene-
sis. Similarly, available evidence based on tissue recom-
bination experiments also supports the view that the
repertoire of inductive interactions is limited and evo-
lutionarily conserved. For example, Nieuwkoop et alii
(1985) show in a comprehensive review of early chor-
date development that, despite the great differences of
morphogenesis among the various chordate orders, the
inductive interactions are remarkably similar. That is,
variation emerges as the result of changes in the con-
text within which the inductive and morphogenetic inte-
ractions are iterated. The structure of the interactions
has remained constant for long periods of evolutionary
time. This conservation of developmental systems is
also illustrated by the vertebrate limb. The " rules" of
limb development have remained remarkably invariant
since at least the Devonian, and probably earlier
(Hinchliffe & Johnson 1980 ; Shubin & Alberch 1986).
In conclusion, the rules of interaction that con-
trol development are limited and general. The itera-
tion of these rules in different contexts can generate
an enormous diversity of patterns. This conceptual
scheme was discussed by O s t e r & Alberch (1982) in an
evolutionary context. As an illustrative example we sug-
gested that a wide variety of epithelial derivatives such
as feathers, scales, glands and teeth could be viewed
as variations within a single morphogenetic process.
Our example was based on simple observation of mor-
phogenetic events such as folding of epithelial layers
of cells (Odell et alii 1981). Edelman et alii (1986) have
recently proposed a specific model of epithelial mor-
phogenesis based on their data on CAMs that integra-
tes gene action, mediated by morphogenetic molecu-
les, with morphogenesis (see Appendix 1). Burke (1988
and in p r e p . ) using this conceptual perspective has spe-
culated that a wide variety of structures, such as hairs,
glands, feathers, scales and even limbs and the cara-
pace of turtles, can be viewed as variations within a
single system of epithelial-mesenchymal interactions
(fig. 14). This scheme is, perhaps, analogous to Wil-
der's cosmobiotic series, in the sense of these structu-
res being ontogenetic and phylogenetic expressions of
variations within a single developmental system. The
key issue here is that morphological nevelty is not the
result of addition of new genes but of the iteration of
the same rules in different contexts (see Nijhout et alii
1986 for treatment of this conceptual issue using com-
puter simulations).
 - -
4. R E C U R R E N C E OF SIMILAR M O R P H O L O G I E S IN DIFFE-
RENT TAXA IS A REFLECTION OF THE INVARIANT AND
FINITE STRUCTURE OF DEVELOPMENTAL INTERACTIONS
Empirical data supports the view that morpholo-
gical transformations are the result of regulation within
an invariant set of interactions rather than the outcome
of the addition of qualitatively new genetic informa-
tion. I f this is the case, transformations are not para-
meter specific ; changes in a wide variety of parame-
ters can result in identical transformations (Appendix
II). Therefore, convergences and parallelisms should
be commonplace in evolution, since they are a reflec-
tion of the internal order and potentially of the system.
Again this property can be illustrated both at the
level of intracellular and epigenetic controls of deve-
lopment. For example, data f r o m transdetermination
(fig. 4a) and homoeotic mutations indicate that certain
states are more stable than others and certain transfor-
mations more likely. For example, the first thoracic seg-
ment appears to be a " s i n k " - a default option when
cell homoeotic genes are turned " o f f " . The relevance
of the genetic control of segment specification in the
evolution of insects has recently been discussed by Raft
& K a u f f m a n (1983).
This lack of morphological "specifity" at this
most basic level of gene control of development was
already emphasized by Goldschmidt (1940) ; in his dis-
cussion of the evolutionary implications of phenoco-
pies, he writes :
" M u t a n t and phenocopy, then, look alike because
changed genetic action as well as action by a phenoco-
pic agent is limited to definite tracks. There can be no
doubt that in the last analysis the primary change pro-
duced both by phenocopic agent and mutated heredi-
tary material must be of a chemical nature. But there
is no reason to assume that it is identical in both cases.
E. A S Y N T H E T I C V I E W
An internalist approach to morphological evolu-
tion can provide insights into the nature of evolutio-
nary processes that could not have been obtained using
the externalist approach centered around the concepts
of selection and adaptation. I conclude, however, by
pointing out again that order in evolution is a combi-
nation of deterministic agents at two levels : internally
generated order based on the internal dynamics of deve-
lopment, and natural selection, dependent on the pro-
perties of organism-environment interaction.
Internal factors and external forces are intimately
linked. By selecting on a particular phenotype, the deve-
lopmental system is indirectly affected and this results
46 - -
If the tracks on which a developmental change can run
are prescribed and limited, quite different primary cau-
ses m a y lead to an identical effect : A railroad car will
roll along its track whether pushed by a gang of men,
a locomotive, a small explosive charge, a vagrant breeze
or whatever. I f the push is too great, it will, of course,
be derailed."
The internalist approach focuses on the determi-
nation of the " t r a c k s " available for the railroad car
to move on rather than on the forces that fuel the move-
ment. F r o m an evolutionary point of view, only per-
turbations based on genetic mutation are inherited - an
argument often used to base the study of morphologi-
cal evolution at the level of genes to the exclus.ion of
any other levels of interaction. However, if we want
to understand the organization of the generative
system, we can gain insights by studying the results of
perturbations at any o f the levels of interaction illus-
trated in figure 13b. In fact, one should expect paral-
lel outcomes. For example, returning to G e r h a r t ' s
model of development of the vertebrate body axis
(Gerhart et alii, 1986), an ordered reduction and loss
of head structures can be induced at various levels of
development. It can result by a genetic mutation that
alters the structure of tubulin units and affects their
rate of polymerization - in fact, one can envision a wide
variety of mutations at different loci resulting in an
identical physiological perturbation (e.g. see Wright's
(1934) genetic analysis of head reduction in guinea
pigs). The same morphology can be generated by a per-
turbation in the physico-chemical rates of redistribu-
tion of cytoplasmic determinants after fertilization (e.g.
by U.V. irradiation or cold temperature shock). Also,
if the model is correct, a perturbation at the tissue level,
such as the surgical removal of prospective mesoder-
mal cells prior to gastrulation, should also result in the
loss of head structures. In every case, the morphologi-
cal outcome is identical. A cyclops will always have the
nostrils above the single eye.
in a historically dependent set of "potentialities" [e.g.
the different evolutionary tendencies towards digital
reduction in frogs vs. salamanders (section C ; Alberch
& Gale 1985]. Every stage in evolution has an intrinsi-
cally determined set of possible transformations. After
every phylogenetic transformation the potentiality of
the system m a y be altered (appendix II). Selection, by
determining the probability of survival of each of the
possible transformations, indirectly affects the inter-
nal state of the species.
Most people would accept this synthetic scheme,
reducing the problem to one of relative importance of
 -- 47 --

INITIAL SECONDARY
INDUCTION INDUCTIONS

>

Epithelium

Morphogenesis
J d
e
>
Mesenchyme

g
/

Fig. 1 4 - Interactions between epithelial and mesenchymal populations of cells can result in a wide variety of organs such as hair (a), salivary
glands (b), teeth (c), feathers (d), scales (e, f), limbs (g), turtle carapaces (h) among others. These various organs can be classified
according to the developmental events involved in their genesis. They fill begin with an initial induction that triggers the formation
of an epithelial thickening and a mesenchymal condensation. This inductive event is followed by a series of morphogenetic foldings
of the epithelial layer. The epithelial layer can either invaginate or evaginate (Odell et alii 1981). Morphogenesis is followed by
a series of secondary inductions that trigger tissue specific gene expression. A further division can be established in organ systems
in which the evagination is followed by an epithelial outgrowth that draws mesenchymal cells into the epithelial sac. Examples of
such type of development can be observed in the limb bud(g) and the turtle carapace (h). (Adapted from Burke 1988).

Des interactions entre des populations de cellules 6pithdliales et m6senchymateuses peuvent aboutir/l une grande varidt6 d'organes
comme les cheveux (a), les glandes salivaires (b), les dents (c), les plumes (d), les ~cailles (e, f), les membres (g), les carapaces de
tortues (h) parmi d'autres. Ces organes varies peuvent ~tre class6s selon les 6v6nements du d6veloppement impliqu~s dans leur gen~se.
Ils commencent tous par une induction initiale qui d~clanche la formation d'un ~paississement 6pith61ial et d'une condensation m~senchy-
rnateuse. Cet 6v6nement inductif est suivi par une s6rie de plissements morphog~n&iques de l'assise 6pith61iale. Celle-ci peut soit
s'invaginer soit se d~vaginer (Odell et alii 1981). La morphogen~se se poursuit par une s6rie d'inductions secondaires qui d~termi-
nent l'expression g~nique sp~cifique des tissus. Une division suppl~mcntaire peut ~tre 6tablie pour les syst~mes organiques chez les-
quels apr~s l'6vagination, l'excroissance de l'@ith~lium attire les cellules m6senchymateuses dans le sac 6pith61ial. Les exemples
de ce type de d~veloppement peuvent ~tre observes pour les bourgeons de membres (g) et les carapaces de tortues (h). (Adapt~ d'apr~s
Burke 1988).
 --
internal constraint vs. natural selection. Traditionally,
internal factors have been considered to play a relative
to the powers of natural selection. This preference
clearly depends on the kinds of questions in which one
is interested. I could rhetorically respond, with the often
used argument that the role of selection is secondary,
since the realm of possible phenotypes is internally
determined, a fact that reduces the role of selection to
a negative agent, i.e. one that only eliminates less adap-
Led forms. This argument, although correct, would be
as misleading as the suggestion that selection can effec-
tively achieve anything.
From this perspective, it is obvious that the argu-
ment of selection vs. internal contraint is not a valid
CONCLUSION
This paper has been an attempt to outline an ope-
rational approach to the integration of development
and evolution as well as to briefly explore some of its
conceptual foundations. As F u t u y a m a (1986, p. 440)
states in his recent textbook of evolution : " T h e impor-
tance of development and historical contingency has
always been recognized, but until recently it has been
the kind of formal, polite recognition accorded to a
stranger at an otherwise intimate p a r t y " . In my view
the reason why development has not been integrated
into the existing corpus o f evolutionary theory is not
a technical one (the " w e do not know enough about
development" type of arguments) but a philosophical
one. To successfully study the role of development in
evolution, one needs to replace the orthodox school of
thought, dating back to Aristotle, of nature as a con-
tinuum, which has become entrenched into the Darwi-
nian theory of evolution (Lovejoy 1936), with an alter-
native philosophy, whose roots can be found perhaps
in Hegel - a theory based on a more dialectical and dis-
continuous view of nature. The latter approach empha-
sizes the interactive aspects of natural processes and
studies them on the basis of the constraints emerging
from such interactions. This is the essence of the inter-
APPENDIX I
Examples of networks of "developmental interactions"
At various points throughout this paper, I have
invoked the properties of " t h e structure of interac-
tions" that characterize developmental systems. This
is an abstract concept that I would like to make more
precise by providing a few examples from selected refe-
rences. The purpose of this appendix is not to review
the models. For information on the specific details of
the models I refer the reader to the original papers.
Development is basically a very complex sequence
of biochemical reactions, which could, at least in
48 --
one. Nevertheless, since there are limits to how much
complexity can be included in any given model while
maintaining its predictive value, the dichotomy is use-
ful since it discriminates between two qualitatively dis-
tinct research programs. I would like to suggest that,
at this stage in the development of the field, it is more
useful to study the organization and evolution of form
f r o m the internalist perspective. This approach, based
on an understanding of development, naturally incor-
porates the phenomena of regulation, integration and
constraint that are inherent to the concept of organism
(i.e. form) and which are absent in the conceptual fra-
mework provided by the externalist approach which
tends to view the phenotype as a static entity.
nalist approach - the search for rules of interaction and
transformation. Evolutionary processes m a y or may
not be continuous, but the internal forces that fuel the
process are few and discrete. It is because of this pro-
perty that I hope that a theory that studies f o r m not
in terms of historical contingency and functional
demands but rather on the basis of the properties of
its internal rules of assembly is possible. Monsters are
a good starting point towards such a goal ; they repre-
sent forms which lack adaptive function while preser-
ving structural order. There is an internal logic to the
genesis and transformation of such morphologies and
in that logic we may learn about the constraints on the
normal.
Acknowledgements
This paper was written while the author was
Fellow-in-Residence at the Neurosciences Institute of
the Neurosciences Research P r o g r a m in New-York. i
thank Paul Elias for comments, Emily Gale for tech-
nical assistance and Lazlo Meszoly for the artwork.
Support was provided by The Simon Guggenheim
Foundation and NSF grants BSR 84-07437 and DCB
86-09073.
theory, be described in mathematical terms. One of the
simplest cases of "kinetic reaction" involves two "well-
stirred" (i.e. uniformly distributed troughout the reac-
tion volume) chemicals, A and B, which react with each
other in a reversible manner. This reaction can be repre-
sented as,
kl
A ~ B
k2
where k I and k2 denote the rate constants for the for-
ward and back reactions. If the two products react in
a linear fashion the equation of motion for this system
 --
is then, d A / d t = k2B - kiA and similarly for B. Thus,
we can describe the rules of chemical interaction in the
form of rate equations. Once the rules are known and
cast in mathematical form, standard analysis can be
used to investigate their stability properties, phase-
transitions and distribution of steady states (see appen-
dix II). It is important to realize, however, that these
properties are not encoded in the variables, A and B,
nor in parameters such as the rate constants, rather they
are a property of the form of the dynamical equation.
The structure of the mathematical equation describes
the nature of the interactions and determines proper-
ties such as stability, and transition probabilities which
are the subject of this paper.
The equation given above was selected because of
its simplicity. It is not, however, very representative of
real developmental processes. Most developmental
systems are not "well-stirred" systems, rather one of
the basic properties of development is the generation
of spatially heterogeneous distributions of molecules,
cells and tissue types. The vehicle for dealing with the
dynamics of such spatially distributed systems is the
theory of partial differential equations in which the
equations of motion become field equations as they are
known in physics. Most mathematical models descri-
bing pattern formation during development are deri-
ved from the notion, originally proposed by Turing
(1952), that spatial heterogeneity can emerge from an
originally homogeneous state by means of diffusion-
driven instabilities. Basically, these models involve a
set of two or more chemicals that diffuse at different
rates and react with each other in a specific enzyme-
A P P E N D I X II
Parameter space and transformational diagrams:
the developmental basis of phenotypic stability and
ordered evolutionary transformation
Parameter space
Theory of pattern formation centers around the
concept of a particular phenotype, P, emerging as the
result of a series of temporal and spatial interactions
during development (appendix 1). These interactions
are regulated by a series of genetically controlled mor-
phogenetic parameters, (xi, i = 1,2 .... m), which can
either be molecular properties such as diffusion and
kinetic rates, or phenomenological variables, such as
elastic properties of the extracellular matrix, cell moti-
lity rates, degree of cell adhesion, etc. In general, the
relationship between the morphogenetic parameters and
the phenotype can be mathematically stated as,
p = f (xi)
where f is an unspecified function describing the nature
of the interactions (see references in appendix 1, for
specific examples of functional forms), while x i is a
finite number of interacting morphogenetic parameters.
49 m
substrate (activator-inhibitor) manner (fig. 15). Mein-
hardt (1982) has extensively reviewed this kind of
diffusion-reaction models and Oster et alii (1988) have
recently reviewed the basic types of pattern generation
mechanisms and discussed some of its evolutionary
implications.
Meinhardt (1984 and 1986), also using an
activator-inhibitor system of interactions, models the
segmentation and compartmentalization events that
characterize early insect development (fig. 16 a-b). As
I discuss in section D. 3, advances in molecular bio-
logy make it possible to identify some of the gene pro-
ducts involved in these interactions (Meinhardt 1986).
Note, however, that the properties of the activator-
inhibitor system of interactions are not encoded in the
genome. That is, the segmentation pattern is not enco-
ded in the so called segmentation genes ; it emerges as
the result of the interactions illustrated in figure 16 a.
Finally, Gatlin et alii (1986) have proposed a model
integrating gene activation and morphogenesis to
explain feather pattern formation. The model is based
on the known properties of L-CAM, a glycoprotein that
mediates cell-cell adhesion. Their model depicts the
interactions between the dermis and epidermis during
the process of pattern formation (fig. 16 c-d). The para-
meters of the model were experimentally perturbed
using antibodies and the perturbations numerically
simulated. The agreement between the experimentally
generated morphologies and the numerically simulated
patterns support the validity of the hypothesized
pattern-generating interactions.
If we know the form of the pattern-generating
function, we can construct a diagram in which for every
combination of parameter values we have a correspon-
ding phenotype, such a diagram is known as parame-
ter space (fig. 17). This figure illustrates a hypotheti-
cal parameter space composed of six phenotypes, A,
B, C, D, E, F determined by the developmental inte-
ractions of two parameters x~ and x2. There are seve-
ral general conclusions about the properties of pattern
formation models than can be illustrated using this
figure.
1. Many combinations of parameter values will
result in the same phenotype, i.e. there is no one-to-
one correlation between genetically or environmentally
mediated changes in parameter values and phenotypic
transformation.
2. The stability of a particular phenotype is
directly related to the area (volume, if more than two
dimensions are involved) of its domain in parameter
space. A larger domain implies that a broader range of
parameter values will result in an identical phenotype.
 -- 50 --

Fig. 1 5 - Schematic depiction of a diffusion-reaction model.

Two molecules, an activator and an inhibitor diffuse at different rates. The
inhibitor diffuses faster than the activator. The activator exhibits autoca-
Activator ir talysis, i.e., its rate of production at a particular point in space is propor-
tional to the amount already present and it is destroyed at a rate proportio-
SLOW nal to the amount of inhibitor present. The inhibitor, in turn, is synthesi-
zed at a rate proportional to the amount of activator present. This system
DIFFUSION exhibits the property of local activation and lateral inhibition required to
generate stable spatial patterns.
Description sch~matique d'un module de diffusion-r~action.
Deux mol6cules, un activateur et un inhibiteur diffusent Adiff6rentes vites-
ses. L'inhibiteur diffuse plus rite que l'activateur. L'activateur far de l'au-
tocatalyse, c'est-A-dire que son taux de production b. un point particulier
de l'espace est proportionnel ~tla quantit~ d6j~t pr6sente et qu'il est d~truit
/t une vitesse proportionnelle ~tla quantit6 d'inhibiteur pr6sente. En revan-
che t'inhibiteur est synth&is6 ~tun taux proportionnel a la quantit6 d'acti-
Inhibitor v vateur pr6sente. Ce systbmeposs~de les propri6t6s d'activation locale et d'in-
hibition lat6rale, requises pour g6n6rer des motifs spatiaux stables.
FAST
DIFFUSION

Fig. 1 6 - Two models of pattern formation illustrating how a system of interactions

can generate stable spatial patterns.
A and B : Diagram of molecular interactions (A) proposed by Meinhardt
(1984) to explain the generation of primary intrasegmental pattern forma-
tion in insects (B). It is assumed that the initial step in the determination
of segments is the formation of a periodic pattern of three different ceil
types / S, A, P. A juxtaposition of S and P leads to the formation of a
segment border. The diagram in (A) proposes that a spatial sequence of
three or more structures can be generatedif three autocatalytic feedback
A B loops exist (S, A, P) that locally) compete with each other (e.g. via a com-
mon inhibitor R) but support each other over a long range. Line indicates
short-ranging substances, dotted lines depict long-ranging interactions. C
and D : Computer model of feather pattern formation proposed by Gallin
et alii (1986). (C) Epidermal cells (L) linked by the cell adhesion molecule,
/X\ I-- l
/I
L-CAM, produce a signal (Es). Dermal cells in mesenchyme (R) res-
\\ // pond to E s by increased mitosis (M), by production of another
cell adhesion molecule, N-CAM (N), and by production of ano-
- .+ ther signal (Ds). D s induces placode formation (P) and down regu-
lates epidermal production of E s. Graph at right shows plots of
the production of E s as a function of the level of D s. (D) Spatial
pattern of mesodermal cell condensation that accompanies feather
pattern formation. This pattern can be generated by the model out-
lined in (C).
C L .......... -+- . . . . P 1.0I\\ Deux categories de modes de formation illustrant comment un
syst~me d'interactions peut g~n~rer des motifs spatiaux stables.
A et B : diagramme d'interactions mol6culaires (A) propos6 par
Meinhardt (1984) pour expliquer la fabrication des motifs intra-
R .............. %-~ N
segmentaux primaires chez les insectes (B). I1 est suppos6 que l'6tape
initiale dans la d6termination des segments correspond ~ la for-

I"'
Ds mation d'un motif p6riodique de trois types cellulaires diff6rents
(S, A, P). La juxtaposition de (S) et (P) conduit ~t la formation
d'une limite de segment. Le diagramme (A) propose qu'une
s6quence spatiale de trois structures, ou plus, peut ~tre g6n6r6e s'il
existe trois boucles de "feedback" autocatalytiques (S, A, P) qui
localement sont en comp6tition les unes avec les autres (e. g. via
un inhibiteur comme R), mais s'entrainent mutuellement ~. long
o~o~,oa terme. Les traits pleins indiquent les effets A court terme, les poin-
,,,o;,o;o; till6s d6crivent les interactions ~ long terme. C et D : mod61isa-
"O'O"O"" tion du mode de formation des plumes propos6 par GaUin et alii
o.O~O~O (1986). C. Les cellules de l'6piderme (L) li6es par une mol6cule
d'adh6sion cellulaire, L-CAM, produisent un signal (Es). Les cel-
_~O=O=O lules du derme dans le m6senchyme (R) r6pondent ~ Es en aug-
WidOW mentant la mitose (M), en prodnisant une autre mol6cule d'adh6-
sion cellulaire, N-CAM (N), et en produisant un autre signal (Ds).
Ds induit la formation de placodes (P) et limite la production de
Es par l'6piderme. La courbe de droite sch6matise la production
de Es en fonction du niveau de Ds. D. Motif spatial des massifs
cellulaires m6sodermiques qui accompagnent la formation des plu-
mes. Ce motif peut 8tre obtenu ~t partir du mod6le expliqu6 en C.
 m51
For example, phenotype B, which has a relatively small
domain should, ontogenetically and phylogenetically, be
less stable than, say, phenotype D. Thus, the area of
a domain in parameter space is equivalent to Wadding-
ton's concept of canalization (e.g. Waddington 1957).
3. The lines drawn in figure 17 correspond to sets
of critical (xl, x2) values. They correspond to trans-
formational boundaries among phenotypes, i.e, a small
perturbation across the threshold value will result in
a qualitative change in phenotype. These boundaries
are known, in the jargon of dynamical system theory,
as bifurcation boundaries (see Oster & Alberch 1982
for additionnal discussion on this issue). Examination
of bifurcation boundaries suggests that many different
perturbations in both parameter values can result in an
identical phenotypic transformation.
This property relates to the discussion in section
D. 4, on the "genetic non-specificity" of phenotypic
transformation. The structure of the bifurcation boun-
daries in parameter space is the evolutionary relevant
property (the railroad tracks in Goldschmidt's quote
(p. 45 or Waddington's chreods), not the specific per-
turbation pushing the system over the threshold.
4. The stability of a particular population of phe-
notypes will depend on its position in parameter space.
For example, let us assume a species (Sp. 1) which exhi-
C F
Fig. 17 -- Parameter space. X
Espace param~trC
m
bits phenotype D (which per se is a very stable one).
However, the distribution of parameter values for the
members of species 1 places them near a bifurcation
boundary (fig. 17). Any small perturbation that would
increase the values of one, or both, of the morphoge-
netic parameter values would trigger a phenotypic
transformation from D to either E or F. One would
predict the phenotype of this species to be fairly uns-
table, in the sense that polymorphisms should be gene-
rated at relatively high frequencies. Conversely, spe-
cies 2 has a more stable phenotype A due to its solid
position in the center of the domain (see section B. 1
for empirical examples o f these properties).
Transformational diagrams
From the structure o f a specific parameter space
(e.g. fig. 17), we can derive information about the rela-
tive probabilities of occurrence of specific phenotypes
as well as about the most probable pathways of trans-
formation. This analysis is completely independent of
any considerations about the relative adaptation of the
possible phenotypes.
In general, one would expect the most stable
phenotypes (i.e., the ones with broader domains in
parameter space) to be the most probable. For exam-
ple, phenotype D is more likely to evolve than B in
figure 17.
E
\
X!
 - - 52 --

.X" Fig. 18 - - Transformational diagram corresponding to the parameter

space illustrated in fig. 17.

Letters correspond to phenotypes, while arrows depict pos-
sible transformations.
Diagramme de transformation correspondant/l l'espace
paramdtrd de la fig. 17.
Les lettres indiquent des ph~notypes tandis que les fl~ches
d~crivent les transformations possibles.

lspecies I I Isp~ci~ 21

e\ /,,e
~ . ,,%
/ e e
Fig. 19 --Species-specific transformational diagrams illustrating the kinds of phenotypic variations that is
likely to appear in species 1 (sp. 1), characterized by phenotype D and species 2 (sp. 2) characteri-
zed by phenotype A (from fig. 17). Thicker arrows represent transformational pathways more pro-
bable than the ones depicted by thin arrows.

Diagrammes de transformation illustrant les categories de variation ph6notypique qu'il est vrai-
semblable de voir appara~tre dans l'esp~ce 1 (sp. 1), caract@is6e par le ph~notype D et dans l'es-
p~ce 2 (sp. 2) caract@is6e par le ph6notype A (d'apr~s fig. 17). Les fl~ches 6paisses repr~sentent
les itin6raires de transformation les plus probables.
 - -
This fact does not m e a n t h a t D wilt b e c o m e evo-
l u t i o n a r i l y " f i x e d " as a species. It c o u l d be t h a t B is
a highly a d a p t i v e p h e n o t y p e a n d D c o r r e s p o n d s to a
lethal t e r a t o l o g y . Then, in spite o f the r e p e a t e d a p p e a -
rance o f p h e n o t y p e D in the p o p u l a t i o n , selection will
push the s y s t e m t o w a r d s B a n d m a k e it the n o r m . This
hypothetical scenario illustrates the interaction between
c o n t r a v e n i n g internal a n d external forces in e v o l u t i o n
(fig. 18).
If we a s s u m e t h a t genetic m u t a t i o n s result in rela-
tively small q u a n t i t a t i v e changes in m o r p h o g e n e t i c
p a r a m e t e r values, we can further our analysis a n d trans-
f o r m the p a r a m e t e r space, c o r r e s p o n d i n g t o P = f
(xl, x2) in figure 17), into a k i n e m a t i c g r a p h d e p i c t i n g
all possible p a t h w a y s o f t r a n s f o r m a t i o n s a m o n g phe-
n0types (fig. 18). I refer to this g r a p h as a t r a n s f o r m a -
tional d i a g r a m . This t h e o r e t i c a l c o n s t r u c t is c o n c e p -
tually a n a l o g o u s to the e m p i r i c a l l y derived g r a p h s
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