martinez & esposito - causación multinively otros enfoques complejos en la biología
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Martínez y Esposito muestran un conjunto de enfoques que demuestran la complejidad desarrollada en los estudiosbiológicos con una propuesta de poder utilizar estos aportes para el estudio de la ciencia en generalTRANSCRIPT
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REVIEW ARTICLE
Multilevel Causation and the Extended Synthesis
Maximiliano Martnez Maurizio Esposito
Received: 24 April 2013 / Accepted: 29 November 2013 / Published online: 27 February 2014
Konrad Lorenz Institute for Evolution and Cognition Research 2014
Abstract In this article we argue that the classicallinear
and bottom-up directedmodels of causation in biology,
and the proximate/ultimate dichotomy, are inappropriate
to capture the complexity inherent to biological processes.
We introduce a new notion of multilevel causation where
old dichotomies such as proximate/ultimate and bottom-up/
top-down are reinterpreted within a multilevel, web-like,
approach. In briefly reviewing some recent work on com-
plexity, EvoDevo, carcinogenesis, autocatalysis, compara-
tive genomics, animal regeneration, phenotypic plasticity,
and niche construction, we will argue that such reinterpre-
tation is a necessary step for the advancement of the
Extended Synthesis.
Keywords Bottom-up approach Extended Synthesis Multilevel causation Proximate/ultimate dichotomy
One of the specific and critical aims of the Extended
Synthesis program is to identify and explain the causal
forces present in developmental mechanisms that play an
essential role in the evolution of form (Pigliucci and Muller
2010). The question about the origin and causal mecha-
nisms of organismal form concerns the interface between
evolution and development. Orthodox explanations that
focus on natural selection as the only source of speciation
and morphogenesis need to be complemented with devel-
opmental, physical, and systemic explanations in order to
obtain a more adequate and complete elucidation of the
causes of biological form. To integrate these causal
mechanisms with natural selection is also a long-term goal
of the evolutionary developmental biology (EvoDevo)
research program. Two different but related concerns are
pivotal to this aim: (1) how development (broadly con-
ceived) causally influences evolution, and (2) how evolu-
tion has causal effects on development.
Of course, such concerns are not new (Reif et al. 2000;
Olsson et al. 2010; Pigliucci and Muller 2010). However,
as many scientists and philosophers have stressed in the
last decades (e.g., Hamburger 1980; Gottlieb 1992; Gilbert
et al. 1996; Love 2003, 2006; Amundson 2005), develop-
mental biology only received scanty attention in the
Modern Synthesis (MS henceforth). For most of the MSs
architects, development was not a central phenomenon to
investigate because it simply followed from the instruc-
tions contained in the genes previously selected. Certainly,
as we will argue, the wide acceptance of Mayrs famous
distinction between proximate and ultimate causes did not
help. It further enlarged the gulf between development and
evolution. Mayrs dichotomy indeed assumed that the
causal mechanism of natural selection was the ultimate
cause behind the emergence of genetic programs imple-
menting and directing development. Development was
therefore conceived as an effect, a consequence of natural
selection. However, the 19th-century developmental tradi-
tion (Esposito 2013), which attracted some now overlooked
biologists even in the 20th century (including Garstang, De
Beer, Svertsov, Schmalhausen, Waddington, Goldschmidt,
and Kuhn), is reemerging in new guises. Many contem-
porary developmental biologists are revisiting, now
armored with fascinating new observations and hypotheses,
the idea that development can have a fundamental role in
the emergence of novelties in evolution (e.g., Muller and
M. Martnez (&)Departamento de Humanidades, Universidad Autonoma
Metropolitana-Cuajimalpa, Mexico City, Mexico
e-mail: [email protected]
M. Esposito
Departamento de Filosofa, Universidad de Santiago de Chile,
Santiago, Chile
123
Biol Theory (2014) 9:209220
DOI 10.1007/s13752-014-0161-3
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Newman 2003; West-Eberhard 2003). More and more
biologists, including geneticists, question the simple and
straightforward causal relation between genotype and
phenotype, i.e., genetic programs and developmental
outcomes (e.g., Noble 2013). The organism is increasingly
seen as a hierarchical system in which different levels of
organization interact in complex ways. Thus, organisms are
not the mere product of closed genetic programs, but the
result of an interactive co-determination among evolution,
development, and environment (broadly conceived), and
between higher and lower levels of biological organization.
In the light of this more complicated picture, a central
question to be addressed is: can we still inquire about these
multiple organismal co-determinations using our tradi-
tional causal models in biology? In fact, many authors have
recently pointed out the difficulty of understanding these
causal relationships using the proximate/ultimate dichot-
omy (West-Eberhard 2003; Amundson 2005; Brigandt
2007; Laubichler and Maienschein 2007; Plutynski 2008;
Laland et al. 2011; Martnez 2011; Mesoudi et al. 2013)
and the bottom-up causal model (Gilbert and Sarkar 2000;
Strohman 2000; Noble 2006), both of which are deeply
entrenched in our scientificand even in our vernacular
epistemology. We sympathize with these ideas, and argue
here that a proper causal framework appropriate to the
Extended Synthesis is required in order to build adequate
models to capture the complex causal interrelationships
that involve entities and processes at different levels of
biological organization. We will suggest that it is possi-
bleattending to theoretical and empirical research on
morphogenesis, niche construction, comparative genomics,
natural selection, autocatalytic networks, phenotypic plas-
ticity, and animal regenerationto build up a new causal
framework that better fits the integrative requirements of
the Extended Synthesis.
Laland et al. have recently argued for a revision of our
old models of causality (2011, 2013). In echoing Levins
and Lewontins (1985) old notion of dialectical biology,
Laland et al. propose a new causal model uncovering dis-
parate observations and disciplines: from EvoDevo to
niche construction, from human cooperation to cultural
evolution. For them, all these disciplines suggest forms of
causation that are irreducible to unidirectional and linear
causal processes. Phenomena related to developmental
biology and niche construction are certainly paradigmatic
examples illustrating why we need a new model they call
reciprocal causation.
In this article we share part of the proposal of Laland
et al. (2013). We agree that Mayrs old dichotomy is today
deeply problematic and a new causal model is required.
However, we think that the notion of reciprocal causa-
tion is unnecessarily limited; it only captures a part of the
biological phenomena. Even though many mechanisms
operating behind the emergence of evolutionary novelties
can be very well characterized by a model of reciprocal
causation, we think that additional forms of causal inter-
action need also to be mentioned, i.e., forms of causation
where physical constraints, genetic and non-genetic
inheritance, stochastic events, and self-organization are
considered. This is especially important in the light of
recent critiques of the model of reciprocal causation that
Dickins and Barton (2013) have made. In particular, the
authors argue that in invoking a dynamic interaction
between development and evolution, Laland et al. are
assuming what they pretend to criticize: the proximate/
ultimate distinction. Indeed, Dickins and Barton claim, two
interacting things must be logically different. If both
development and evolution remain two distinct processes
(though connected), we can still defend the idea that
development and evolution have their own causes (which
implies specific why and how questions). As a con-
sequence, Laland et al. do not replace Mayrs dichotomy,
they only make the trivial observation that there is some
kind of connection between ultimate and proximate causes
(Dickins and Barton 2013).
But the critiques of Dickins and Barton do not apply to
our multilevel causation model (MC). Indeed, MC does not
merely describe the relation between evolution and
development. We are not talking about two things in
interaction. We are talking about one process (the organ-
ism) in interaction with several other processes (including,
of course, evolution and development).1 From a more
general perspective, with MC we refer to all the processes
and interactions that are behind the origination and evo-
lution of the organismal forms (from bacteria to eukary-
otes, including dynamic entities such as super-organisms).
For this reason we propose taking MC as an ideal candidate
to be placed at the base of the causal framework men-
tioned, replacing the traditional causal concepts prevalent
in biology, and extending the notion of reciprocal causa-
tion. We also hope that placing MC as a touchstone of
integrationist causal models will help to promote a deeper
inclusion of theories of complexity in the Extended Syn-
thesis agenda.
Rethinking Causation in the Extended Synthesis
During the last decade there have been important argu-
ments calling into question the traditional causal approa-
ches to evolution and development (Gilbert and Sarkar
2000; Thierry 2005; Laland et al. 2011). Specifically, these
arguments focus on the necessity to (1) reconsider the
1 On the organism conceived as a processual entity see Woodger
(1929) and Dupre (2012).
210 M. Martnez, M. Esposito
123
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dichotomy of proximate/ultimate causes, and (2) comple-
ment the bottom-up causal model with a top-down one. Let
us see what the criticisms are.
The Proximate/Ultimate Causal Dichotomy
In a well-known and very influential paper published in
1961, Mayr introduced the dichotomy between proximate
and ultimate causes to clarify the notion of causation in
biology. Mayr pointed out the separation between func-
tional biology and evolutionary biology: two areas with
their own methods, goals, and basic concepts (Mayr 1961).
Mayrs argument does not need to be restated here, but it is
worth remembering two main points: (1) Mayrs dichot-
omy has been amply accepted in biology. (2) The dichot-
omy not only had explanatory value; it also had an
undeniable ontological dimension by referring to two dif-
ferent kinds of causes that produce different types of bio-
logical results. The dichotomy separates the nature of
physiological and phylogenetic processes: their operation
and their biological consequences are independent (Mayr
1961). As Amundson (2005, p. 99) has put it: Proximate
causation involves the processes in an individuals lifetime,
and ultimate causation involves the historical origins of the
characters of an individual organism. After 1970 the
dichotomy was mainly used to refer to developmental
processes as proximate and, therefore, irrelevant to evolu-
tionary explanations (p. 212).
However, Amundson himself argues that ontogeny can
be understood as a dynamic process in a causal continuous
chain. Development can be seen as an intermediary stage in
a causal (neither dichotomous nor contrasting) continuum.
Amundsons view implies the coherent idea that the bio-
logical world is not deeply divided into two kinds of causes
(requiring two kinds of explanations); on the contrary,
biological causation in the generation and evolution of
form seems to be a complex matter that goes far beyond
such idealizations. It incorporates many entities and prop-
erties at diverse levels of organization and at different time
scales (Huang 2000; Newman 2003b; Riedl 2005; Thierry
2005; Plutynski 2008).
Amundson is not alone in criticizing Mayrs dichotomy.
From another perspective, West-Eberhard (2003, 2005) has
argued that Mayrs model is very problematic insofar as
proximate mechanisms, in many cases, produce the varia-
tion on which natural selection works: For evolutionary
biology, proximate mechanisms represent more than just
different levels of analysis of research styles. They are the
causes of the variation upon which selection acts (West-
Eberhard 2003, p. 11). Muller (2005, 2007) has pointed out
that the proximate/ultimate dichotomy stems primarily
from the impossibility of either evolution or development
separately providing a complete causal explanation of
organismal form. This explanatory limitation is prompted
by the particular interpretation of causality held so far by
each field, and rooted in the entrenched polarized image of
remote and proximate causes. Muller et al. suggest that an
alternative to the dichotomy is to consider the two cau-
salities not as opposite, but interrelated (Muller 2005;
Callebaut et al. 2007).
This is also the spirit behind Plutynskis work on
dominance. She has shown how a biologically complex
phenomenon like genetic dominance can only be explained
by taking into consideration a wider causal framework that
goes beyond the proximate/ultimate dichotomy, and
includes both top-down and bottom-up causal approaches.
According to Plutynski (2008), the discrete categories of
proximate and ultimate causes are not useful to explain
general patterns in biology, where it is necessary to
determine the interaction of multiple levels of organization
and connect different time scales. In a similar vein, Bri-
gandt (2007) has argued that such a dichotomy not only
obscures explanations of complex phenomena like evolv-
ability; it also creates unnecessary tensions (e.g., between
typological and population thinking). Thierry (2005,
p. 1182) has similarly argued that the dual proximate/
ultimate model blocks important approaches to the rela-
tionship between evolution and development: it cannot
account for the different scales of the evolutionary time and
for the epigenetic constraints that direct the changes open
to living beings.
Other alternatives recommend removing the dichotomy
altogether. Instead of considering the two causalities
entwined, one suggestion is to build a new causal frame-
work going beyond the dichotomy (Hall 2000; Amundson
2005; Laubichler and Maienschein 2007). This last view-
point, regarding the necessity of a replacement, coincides
with the position that a novel conceptual framework is
required for the Extended Synthesis.
In our opinion, this viewpoint is more fruitful than the
alternatives previously mentioned for two principal rea-
sons. First, and as the critiques of Dickins and Barton
(2013) also show, to try to solve the problems using the
same concepts of proximate and ultimate would not
help much: their usual contrasting meanings are deeply
entrenched in our biological theories and practices, and it
would be extremely difficult and probably hopeless to try
to reform them toward conciliation. It is thought that they
are opposed by nature and that they operate at different
time scales. But new lines of research show how causation
in morphogenesis and evolution is a very complex and
multifarious phenomenon, going far beyond any frame-
work that would result from just taking proximate and
ultimate causes merely as interrelated. We review some of
this work in the next sections to support the proposal of
building a new causal framework for the Extended
Multilevel Causation and the Extended Synthesis 211
123
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Synthesisone that drops the concepts of proximate and
ultimate. We will also explore the possibility of taking
into account both bottom-up and top-down causalities in
the understanding of complex biological phenomena. This
suggestion gives us some clues about the starting point of
the construction of the new causal framework required for
the Extended Synthesis, and leads us to the second theme
of this section.
The Incompleteness of the Bottom-up Approach
The criticisms of reductionism and the bottom-up approach
to biological causalityfrom molecules to ecosystems
are vast and well known. One recent criticism comes from
Noble (2006): the usual reductionist bottom-up model of
causality is insufficient to explain and capture what hap-
pens in the organization and evolution of complex systems.
Noble reminds us of two fatal problems with the bottom-
up approach: computability and relevance. With regard to
the former, he says that even if it were possible to recon-
struct the chemical activity involved in the folding of a
single molecular protein (which would take months of the
most advanced computing), the molecular reconstruction of
the processes of an entire cell, which involves, say, the
interactions of 1,012 molecules, would be practically
impossible. The second fatal problem is that even if it were
possible to calculate the molecular activities of systems,
those findings would certainly be irrelevant:
Structures and processes at a higher level simply are
not visible at the molecular level. The genes and
proteins of the body do not in some way know or
reveal what they are doing in higher-level func-
tions. The assumption that they do is a strange one.
(Noble 2006, p. 78)
We can extend Nobles remarks and say that the issue is
not just a matter of explanation and of epistemological
approaches to biological phenomena; the issue is also onto-
logical. It is a fact that the complexity of biological processes
such as morphogenesis involves systemic developmental
properties that go beyond the molecular level.
Other authors also insist on the inadequacy of the bot-
tom-up approach in the epistemological, methodological,
and ontological domains. Thus Strohman (2000, p. 575)
states:
In biology, molecular reductionism has mostly dis-
tracted us from study of mesoscopic realms between
genotype and phenotype where complex organiza-
tional states exist and where, also exist networks ofregulatory proteins capable of reorganizing patterns of
gene expression, and much other emergent cellular
behavior, in a context-dependent manner.
In a similar vein, Gilbert and Sarkar (2000) argue from an
organismic perspective that bottom-up and top-down
approaches must be used to explain the complex ontology
of biological phenomena: Organicist ontology and expla-
nations would include those bottom-up considerations but
would also include the functioning of the tissue within the
organism, the functioning of the organism within its
environment (2000, p. 2).
Multilevel Causation
Given the discomfort with both the dichotomous and bot-
tom-up approaches, what are the alternatives? The point
made by Newman (2003b), Riedl (2005), Noble (2006),
Plutynski (2008), and Mitchell (2009) is worth developing.
The central idea is that we need to think in terms of a
causal model that includes multiple directions of causation,
which will allow different levels of organization and dif-
ferent time scales to be interrelated. This is not only
desirable in order to have a more complete wide-ranging
theory of the relationship among evolution, development,
and environment; it can also provide a new causal frame-
work required for the Extended Synthesis. Needless to say,
this is mandatory to grasp the biological discoveries made
in recent decades.2 Let us see what the principal virtues of
multilevel causation are.
The Concept of Multilevel Causation
A way to visualize what we mean by MC is the image of a
web of life as recently represented by Raoult et al.
Indeed, the biologists Eugene Koonin, Didier Raoult, and
coworkers have recently stated that the data accumulated in
microbial genomics, and comparative genomics more gen-
erally, demonstrate that genetic information not only flows
vertically, but also laterally (Raoult and Koonin 2012, p. 1).
If lateral transfer of informational genes is much more
widespread than previously expected, our conception of
species and our notion of the tree of life need substantial
2 Multilevel causation is fundamental in organization processes of
biological complexity: in areas of study such as complexity theory
(Kauffman 1993; Emmeche et al. 2000; Hooker 2011), niche
construction theory (Gilbert and Sarkar 2000; Laland et al. 2008),
epigenesis (Newman 2003b), paleontology (Vrba and Eldredge 1984;
Sepkoski 2008), systems biology (Palsson 2006; Trewavas 2006),
cellular autocatalysis (Moreno and Umerez 2000), neurobiology (Ellis
2009), and evolutionary theory (Campbell 1974; Mitchell 2009;
Martnez and Moya 2011), there are many advanced works about the
importance of the co-determination of bottom-up and top-down
causes. This co-determination is seen as a universal pattern of
organization (El-Hani and Queiroz 2005).
212 M. Martnez, M. Esposito
123
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revisions (Merhej and Raoult 2012). In addition, if the
evolution of the genome is characterized by gene deletions
and duplications and insertions and genome rearrange-
ments (Merhej and Raoult 2012, p. 2), this means that
every genome, including the human genome, is a chimera,
i.e., a set of genes with viral, bacterial, and eukaryotic
origins. Yet, such chimerical genomes contain many genes
that do not increase the overall fitness of the organism. As a
consequence, evolution is not only about mutation and
selection, but also about stochastic processes of assortment.
Genomes are thus constituted by genes of different evolu-
tionary lines that cannot be represented by a unique tree of
life. A more complex and intricate picture is required,
which Raoult dubs the web of life (see Fig. 1).
We can use this image of the web of life for visualizing
a web-like model of causation. In fact, it can be argued that
the complex web of life, which resembles an intricate
network more than an ordered tree, mirrors the complex,
multileveled relations that we can observe at different levels
of biological organization, both diachronically and synch-
ronically. In other words, the web of life also reflects a
web of causes where physical constraints, natural selection,
environment, chance, genetic and non-genetic information
interact. Whereas the traditional tree of life can be seen as the
outcome of a unique causal line going from gene mutation
towards selection (ultimate causes), the web of life is the
result of a large assortment of causes. From this perspective,
MC would provide the conceptual framework for consider-
ing how the web of life came about, and the multiple
mechanisms producing it.
One of the main virtues of an MC approach is that it
provides a flexible framework for investigation: there are
neither principal (evolutionary) nor secondary (proximate)
causes that can be neatly distinguished, in principle at least.
There is no fixed frame in which we can a priori establish
where why and how questions are. MC uncovers
diverse types of causationlinear, reciprocal, or top-
downwithout any pretension of reducing or subsuming
one to the other. MC also fosters a pluralist cooperation
among disciplines in assuming that there are neither centers
(e.g., natural selection) nor peripheries (e.g., EvoDevo)
fixed once and for all; what is central and peripheral
changes with the growth of knowledge. In sum, MC is a
descriptive concept denoting the complex causal relations
we find across levels of biological organization.
As a very general definition, with MC we refer to all the
mechanisms of causal determination and co-determination
(i.e., feedback loops), multiply directed (bottom-up and
top-down), that occur between entities and events at dif-
ferent levels of organization, and that connect different
time scales.3
Some of these kinds of causal co-determinations will be
exemplified in the following sections.
Fig. 1 The web ofmitochondria (Merhej and
Raoult 2012)
3 It is worth mentioning that several philosophers (e.g., Kim 1998;
Craver and Bechtel 2007) call into question the notion of top-down or
downward causation, arguing that it presents important difficulties in
its conceptualization. But see Andersen et al. (2000) and Klister
(2010) for a defense of downward causations concept.
Multilevel Causation and the Extended Synthesis 213
123
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Niche Construction and Multilevel Causation
Here we review some work on niche constructionin a
nutshell, the influence of the environment on the organism
and its components. Odling-Smee et al. (2003) define niche
construction as a process in which organisms change the
relation between themselves and their environment.
Organisms not only inherit an ecological niche; they also
transform that niche in each generation. What the authors
argue is that the ways organisms modify their environment
and the modalities through which the environment influ-
ences organisms fitness have important evolutionary out-
comes: Niche construction is itself an evolutionary process
that can potentially codirect and regulate natural selection
and other evolutionary processes (Odling-Smee et al.
2003, p. 133). The reciprocal feedbacks that are established
between organisms and environments defy a simple and
linear model of causation. Evolution is not a process simply
driven from gene mutation and selection, because which
genes are selected (or expressed) also depends on the con-
textual ecological niche (that previous generations of
organisms have contributed to transform).
For Gilbert and Sarkar (2000) there are two higher levels
that regulate genes: cellular cytoplasm and the environ-
ment. With regard to the latter, they mention well-known
examples such us the ant larva becoming a queen or a
worker depending on the food it is given, or a wrasse
becoming a male or a female depending on whether a male
is already in the reef (2000, p. 7). The authors regard these
kinds of influences as downward directed:
These life history strategies make up a large part of
contemporary ecology. However, the proximate
causes for most of these changes are unknown. They
represent top-down regulation wherein the upper
level (the environment) selects the phenotype rather
than the lower level (the genes). To be sure, both are
needed; but the reductionist approach of explaining
the phenotype solely from the component parts of the
lower levels will not suffice. (2000, p. 7)
They add: Whole organisms and their environmental
interactions are becoming studiable, and gene expression
patterns are being seen as being controlled both from the
bottom-up and from the top-down (2000, p. 7)
Laland et al. (2008) go deeper into the study of the
relationship between development, evolution, and envi-
ronment. They describe some remarkable examples of
niche construction and multilevel causation with ontogeny
in the wild.4 It is worth mentioning that, in general, pro-
posals of non-genetic inheritance, such as epigenetic
inheritance, niche construction/ecological inheritance, and
cultural inheritance, adopt instances of multilevel causation
in their analysis that go beyond the dichotomy of proxi-
mate/ultimate (Mesoudi et al. 2013).
Autocatalytic Networks and Multilevel Causation
Other work that incorporates multilevel causation includes
research on autocatalytic networks. The transition from
inorganic to organic chemistry is thought to involve self-
organized networks of molecular arrangements whose
properties give rise to the basic and overall characteristics
of living systems (Lee et al. 1997). Kauffmans (1993)
work on this topic is well known. But do autocatalytic
networks exhibit processes of multilevel causation? This is
proposed by Moreno and Umerez (2000) with regard to
cells: the self-organization of a fundamental system like the
cell is established through the interactions of the whole
system. The functional material that makes up the system is
fabricated within internal processes of the cell itself: the
cause of a given functional component in a cell is the
whole network of (recursive) reactions that constitute the
cell itself (Moreno and Umerez 2000, p. 110). In this way,
the whole system determines what happens to its constit-
uents, representing a case of downward causation. This top-
down determination, in conjunction with bottom-up
determination (from the constituents to the whole) in a
feedback loop, promotes order and complexity in the cell
system. Following hierarchical theory, El-Hani and Que-
iroz (2005, p. 162) define this kind of causal determination
in autocatalytic networks as the influence of the whole over
its components. The higher level of every system imposes
constraints on its parts, affecting its behavior with the
organizational pattern that the higher level determines.
Natural Selection and Multilevel Causation
Multilevel causation has also been applied to describe the
positive causal role of natural selection in the generation of
complex morphology (Campbell 1974; Ellis 2006; Mart-
nez and Moya 2011). Natural selection operating at higher
levels of organization (individual or populational) affects
the configuration of the lower (molecular or genetic) levels
of the next generation. This gives natural selection a cre-
ative causal role in morphogenesis. The point here is that
the fitness of the individuals partly determines the com-
position of the initial molecular conditions of the sub-
sequent generation(s). In other words, if an individual
succeeds in survival and reproduction, its DNA will
4 Such is the case of the female goldenrod gallfly. The proteins
contained in the saliva of the gallfly larva induce a cellular
Footnote 4 continued
proliferation on the goldenrod. A gall is formed and the larva enters in
it and continues to be protected as it feeds.
214 M. Martnez, M. Esposito
123
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(ceteris paribus) be present in the next generation as the
starting point of a new individual. We see, then, a dia-
chronic feedback causal loop in action: what occurs to
entities at higher levels of organization causally affects the
entities of lower levels (in the subsequent generations),
which in turn construct new higher level entities, and so on.
Figure 2 is useful for understanding this mechanism.
The initial conditions of every life cycle are determined
in part by what happened in the previous generation (at the
organismal level). We observe, then, the causal influence of
a higher level (organismal) on a lower level (molecular).
Looking at Fig. 2, if we take the three types of arrows
(thin, thick, dashed) as a causal continuum, we realize the
influence of any past event over the future ones, connecting
different time scales (ontogenetic and phylogenetic). Any
point of the continuum is conditioned by past events, and it
will condition future ones because of the channeling effect
of downward and upward causations operating together.
Ontogeny and Multilevel Causation
Newman, Muller, and colleagues (Muller and Newman
2003; Muller and Olsson 2003; Newman 2003a, b; New-
man et al. 2006) have argued that many of the basic
morphological features of living systems are products of
generic properties that are physically inevitable (and not
encoded in the DNA). The authors study some physical
attributes of cell aggregates and tissues, such as diffusion,
differential adhesion, oscillation, and reactiondiffusion
coupling. This evidence leads them to argue that those
properties were present at the origins of body plans, acting
as causes of their form. Those properties, which persist
entrenched in the development of modern-day organisms,
were the constructional causes of basic features of organ-
ismal form, such as lumen formation, compartment for-
mation, multilayering, segmentation, and so on. Also, the
ancient cell aggregates (metazoan ancestors, 700 mya)
would have behaved like liquids and possessed elasticity,
exhibiting properties of soft matter (excitable media)
(Newman 2003a; Newman et al. 2006). Newman (2003a,
p. 223) writes:
The cells of these primitive aggregates were highly
evolved metabolically, with complex biochemical and
genetic networks; they were open and responsive to
the external environment; and they were capable of
self-organizing dynamical activities under appro-
priate circumstances. For instance, positive and neg-
ative feedback loops of chemical reactivity, when
confined to the interior of an individual cell, will often
lead to temporal oscillations in one or more chemical
component they can readily arise as self-organizingside-effects of the metabolic circuitry , ratherthan as the expression of an evolved program.
Newman et al. (2006) regard three mechanisms as most
important: (1) interactions of cell metabolism with the
physicochemical environment within and external to the
organism; (2) interactions of tissue masses with the phys-
ical environment on the basis of physical laws inherent to
condensed materials; and (3) interactions among tissues
themselves, according to an evolving set of rules:
Because the inherent physical properties, in their self-
organizing capacities, but also conditioned by exter-
nal parameters and extrinsic forces, can act as mor-
phogenetic determinants, the dynamical, constraining
and environmental aspects of developmental causa-
tion can productively be analyzed in the framework
of inherency and interaction, i.e., epigenecist.
(Newman et al. 2006, pp. 290291)
One important fact to mention here is that, as Newman has
pointed out, the descriptions in current molecular develop-
mental biology point the arrow of causation in the upward
direction only. As Newman has put it:
Fig. 2 Natural selectionbetween levels of biological
organization (from Martnez
and Moya 2011)
Multilevel Causation and the Extended Synthesis 215
123
-
The decoupling between genotypic and phenotypic
change in both evolution and development implies that
causality runs in both directions, not that these levels
are causally independent of each other. And because
phenotype is itself a multileveled concept with mor-
phological and biochemical aspects, determination is
actually multifarious. (Newman 2003b, p. 171)
To summarize: embryo physics follows ahistorical
generic processes of self-organization, present in all com-
plex systems (alive or not). Those epigenetic processes
were present at the very beginning of metazoans, and have
prevailed since then.
Carcinogenesis and Multilevel Causation
Here we want to mention the work of Soto and Sonnenschein
on carcinogenesis (2005). They adopt an organicist
approach instead of the usual reductionist and deterministic
genetic approach, arguing that the somatic mutation theory
(SMT), where cancer is a cellular problem caused by mutated
genes, is inadequate, so an alternative theory is required.
Tissue organization field theory (TOFT) seems appropriate at
this point, because it shows carcinogenesis as a problem of
tissue organization in a developmental process that goes
awry. How is this theoretical dichotomy related to downward
causation acting between levels of organization? In TOFT,
Soto and Sonnenschein (2005, p. 103) write, cancer is placed
in a different hierarchical level of complexity than in
SMT: (1) carcinogenesis represents a problem of tissue
organization comparable to organogenesis, and (2) prolifer-
ation is the default state of cells. The authors assert that this
new theory permits a better and more adequate definition of
the phenomenon, but it implies a switch in the usual way of
seeing living organization:
The unidirectional flow from genes to shape is being
modified to include cell movements that cause physi-
cal stress in neighboring cells inducing specific gene
expression. This causal chain, from a molecular event to
physical stress inducing the next molecular event
appears as an emergent (i.e., an increased number of
cells moving) acting as a downward cause. (p. 115)
Phenotypic Plasticity, Environment, and Ontogeny
Cor van der Weele (1999) lamented the absence of the
environment from developmental biologys textbooks. As
she argued, despite the availability of many observations and
known phenomena, developmental biology still overlooks the
centraland very often determinantrole played by envi-
ronmental parameters in the processes of morphogenesis.
From the aphids development to the butterflys seasonal
polyphenisms, from the sexual determination of echiurid to
the predator-induced polyphenisms in Daphnia cucullata (van
der Weele 1999; Gilbert 2002), all show that the environment
is much more important than commonly believed. If van der
Weele is right, the changing role of the environment in
inducing and influencing morphological traits and behavior
also implies the need to change our causal models of expla-
nation. If the old genetic framework saw genes as the starters
and inducers of a cascade of events heading directly to the
phenotype, now we need to rethink the relations among
genotype, environment, and phenotype as a triadic dynamic
network. In other words, this is an intricate web of causes and
effects where the environment can determine a specific gene
expression, and phenotypes in turn can determine the envi-
ronmental variables that may act on gene selection.
The cases of predator-induced polyphenisms are very
illustrative. They are included in the more general category
of phenotypic plasticity. Indeed, the development and
morphology of many organisms can be deeply shaped by
population density, food, temperature, sex ratios, and the
presence of predators (Gilbert 2002; West-Eberhard 2003).
It is now well known that the morphology of many rotifers
(including Daphnia) changes if development happens in the
presence of predators. For instance, Daphnia cucullata
develops a protective helmet when kairomones (compounds
released by predators) are detected in its environment.
Kairomones dramatically influence the developmental path
of Daphnia; in so doing kairomones also influence its fit-
ness. Apart from rotifers and gastropods, predator-induced
polyphenism is also present in vertebrates and social insects
(Weider and Pijanowska 1993; Passera et al. 1996; Gilbert
2002; Miyakawa et al. 2010).
Environmental causes, including seasonal and nutri-
tional polyphenism, illustrate that causation is not uni-, but
multidirectional: from genotypes to phenotypes, from the
environment to genotypes, and from phenotypes to the
environment. As Gilbert concluded in 2003, we need a
more context-dependent analysis of the causal network
operating behind the origination of organismal morphol-
ogy; we need a biology that must integrate the signals
from the genome, from the interactions between cells, and
from the environment in which the organism develops
(Gilbert 2003, p. 98). A unidirectional model of biological
causation is inadequate for grasping the interactive,
dynamic, and multilevel interactions among environment,
development, heredity, and evolution. In short, we need to
consider a multilevel model of causation.
Animal Regeneration and Morphogenetic Fields
From the celebrated studies of Hans Spemann it was clear
that the phenomena of regeneration and, more generally,
cellular differentiation and morphogenesis were not easily
216 M. Martnez, M. Esposito
123
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explainable with a bottom-up model of causality. In one of
his numerous heteroplastic (interspecific) transplantation
experiments, Spemann (1919) showed that the embryo was
extremely plastic during development. The multiple rela-
tions between the parts and whole could not be easily
accommodated in a linear, upward, causal model. In fact,
only rarely were the transplanted parts strictly determined
at the beginning because, once they were implanted, their
activities changed according to the new environment. In
sum, the activities of transplanted parts always depended
on the activity of the surrounding cell system in which
these new tissues were inserted.
As Spemann illustrated (see Fig. 3), Triturus teaniatus
gastrula (a, left) has a white spot in the middle representing a
transplant of tissue taken from a Triturus cristatuss gastrula (b,
left), and vice versa. The original tissue transplanted in a (left)
would normally become epidermis, but it behaves according
to the new environment into which it is inserted, so it becomes
an eye and part of the brain (a, right). Likewise the original
tissue transplanted in b (left) would normally become the
forebrain and an eye, but in the new environment it forms
epidermis. The last figure (b, right) represents the Triturus
cristatus embryo at an advanced stage of development. Note
the black pigmented cells in the gill area (Spemann 1919,
pp. 588589; see also Hamburger 1988).
In order to explain the plastic property that embryos
exhibited during morphogenesis, Spemann assumed the
existence of a morphogenetic field that could account for
the specific direction of cellular differentiation, i.e., a limb
field produces limb tissue, an epidermis field produces
epidermis cells and so forth. Although the notion of the
morphogenetic field was partially forgotten after the 1960s
(Gilbert 1997), developmental biologists resurrected it in
the 1990s (Davidson 1993; Bolker 2000). In a recent arti-
cle, Levin defines the morphogenetic field as follows:
The quintessential property of a field model is non-
localitythe idea that the influences coming to bear
on any point in the system are not localized to that
point and that an understanding of those forces must
include information existing at other, distant regions
in the system. In a sense, the familiar morphogen
gradient is already a field model, as it refers to
changes of the prevalence of some substance across a
spatial domain, as opposed to a single concentration
level at some local spot. Cells in vivo are immersed
in a number of interpenetrating sets of signalsgra-
dients of chemicals, stresses, strains, pressures, and
electric potential. (Levin 2012, p. 2)
In revising the experiments on regeneration and regu-
lation in planaria, Levin claims that the conceptual use of
the morphogenetic field is more compatible with a top-
down perspective, based on the flow of information at
different, even distant, levels of biological organization.
Fig. 3 Spemanns heteroplastictransplantation experiments on
Newt embryos (1919,
pp. 588589)
Multilevel Causation and the Extended Synthesis 217
123
-
Indeed, as he notes, the process of head regeneration in
planaria prevents the formation of other heads in distal
injured sites. The cells in the posterior axis of the planaria
body behave as if they knew that a head is regenerating
on the other side. Thus, Levin continues, in order to
understand the process of regulation in the planaria body,
single cells are not the most effective units of investigation.
In a morphogenetic approach, higher levels of organization
are required and multilevel forms of causation need to be
considered. In the spirit of Spemanns old proposal, Levin
concludes that a deeper understanding of the phenomena
related to animal regeneration, embryogenesis, and cancer
requires a morphogenetic approach more compatible with a
model of downward causationa perspective that may
also have fundamental implications for our understanding
of evolution, development, and cognition.
Conclusions
The examples of multilevel causation reviewed above
comprise diverse and complex causal relations between
levels of hierarchical organization. What they show is that in
nature there are multifarious mechanisms, interactions, and
connections that permit feedback controls at both intra- and
inter-levels of organization, which can generate order and
complexity in the form and function of biological systems.
This fact has important implications for our usual theoretical
approaches to evolution and development, and calls for a
more inclusive (and non-gene-centered) perspective, like the
one proposed by the Extended Synthesis. In line with Laland
et al.s (2013) proposal, we have asserted here that it is
impossible to use our classical conceptual frameworks to
describe and understand the biological causal complexity
implied by the interface between evolution and develop-
ment. However, we consider Laland et al.s model of reci-
procal causation unnecessarily restricted.
We agree that the ubiquitous phenomena of phenotypic
plasticity offer many of the variants on which natural
selection works. We also agree that organisms often induce
changes in the environment that may increase the fitness
and alter the final selective outcomes. In general, we agree
with Laland et al. that various forms of feedbacks can be
described as reciprocal. But there are other crucial causal
relations happening among the environment, development,
and genomes that cannot be reduced to reciprocal feed-
back. Indeed, once we extend our attention from the rela-
tions between evolution and development to all the causes
working behind the origination of organic forms (from
bacteria to eukaryotes), we need to expand our models of
causation accordingly. The case illustrated by Raoult,
Koonin, and colleagues is exemplar (Merhej and Raoult
2012; Raoult and Koonin 2012). Microbial genomics
shows that evolutionary changes in bacteria are not unidi-
rectional and merely adaptive; they are often the result of
stochastic processes. In order to understand bacterias
morphological variation and evolution, a web of causes
needs to be invoked.
In addition, cellular autocatalytic networks present a
form of downward causation that is systemic rather than
exclusively linear or reciprocal. Feedback controls are only
one out of various types of partswhole relationships. The
properties of self-organization that we can observe in
whole cellular systems are essentially interactive and
characterized by ramified causality. As Moreno and
Umerez describe, the higher levels of a cellular system
impose specific constraints over the composing parts
(2000, pp. 108110). Yet, Spemanns and Levins experi-
ments demonstrate that a morphogenetic field determines
the fate of individual cells: here we have cases of down-
ward causation where reciprocal causation plays only a part
in a broader interconnected whole. Finally, the physical
generic attributes that characterize ontogenyincluding
cases of developmental constraintsare best viewed as yet
another kind of multilevel causation: inner and outer
environments, together with inherent biological properties,
all work behind the constitution of life forms.
In short, if evolution is more than mutation and adaptive
selection, and if linear or dichotomized models of causa-
tion fail in describing lifes complex networks, a wider
approach is necessaryone that includes multiple direc-
tions of causal determination between entities and events at
the diverse levels of organization and at different time
scales. It is in this sense that we advocate the necessity of
using a model based on multilevel causation in the
Extended Synthesis.
Acknowledgments We are grateful to all the members of PhiBio,Seminario de Filosofa de la Biologa UAM-C, for useful discussions.
References
Amundson R (2005) The changing role of the embryo in evolutionary
thought. Cambridge University Press, Cambridge
Andersen PB, Emmeche C, Finnemann NO et al (2000) Downward
causation: minds, bodies, and matter. Aarhus University Press,
Aarhus
Bolker JA (2000) Modularity in development and why it matters to
evo-devo. Amer Zool 40:770776
Brigandt I (2007) Typology now: homology and developmental
constraints explain evolvability. Biol Philos 22:709725
Callebaut W, Muller GB, Newman SA (2007) The organismic systems
approach: streamlining the naturalistic agenda. In: Sansom R,
Brandon RN (eds) Integrating evolution and development: from
theory to practice. MIT Press, Cambridge, pp 2592
Campbell DT (1974) Downward causation in hierarchically organised
biological systems. In: Ayala FJ, Dobzhansky T (eds) Studies in
the philosophy of biology. MacMillan, London, pp 179186
218 M. Martnez, M. Esposito
123
-
Craver CF, Bechtel W (2007) Top-down causation without top-down
causes. Biol Philos 22:547563
Davidson EH (1993) Later embryogenesis: regulatory circuitry in
morphogenetic fields. Development 118:665690
Dickins TE, Barton RA (2013) Reciprocal causation and the
proximateultimate distinction. Biol Philos 28:747756
Dupre J (2012) Processes of life: essays in the philosophy of biology.
Oxford University Press, Oxford
El-Hani C, Queiroz J (2005) Downward determination. Abstracta
1:162192
Ellis GFR (2006) Physics and the real world. Found Phys 36:227262
Ellis GFR (2009) Top-down causation and the human brain. In:
Murphy N, Ellis G, OConnor T (eds) Downward causation and
the neurobiology of free will. Springer, Berlin, pp 6381
Emmeche C, Kppe S, Stjernfelt F (2000) Levels, emergence, and
three versions of downward causation. In: Andersen PB,
Emmeche C, Finnemann NO, Christiansen PV (eds) Downward
causation. Aarhus University Press, Aarhus
Esposito M (2013) Romantic biology18901945. Pickering and
Chatto, London
Gilbert SF (1997) The re-discovery of morphogenetic fields. DevBio:
a companion to Developmental Biology, 8th edn. Sinauer, Sunder-
land. http://8e.devbio.com/article.php?ch=3&id=18
Gilbert SF (2002) Predator-induced polyphenism. In: Tickle C (ed)
The encyclopedia of life sciences, vol 15. Macmillan, London,
pp 134138
Gilbert SF (2003) The reactive genome. In: Muller GB, Newman SA (eds)
Origination of organismal form: beyond the gene in developmental
and evolutionary biology. MIT Press, Cambridge, pp 87101
Gilbert SF, Sarkar S (2000) Embracing complexity: organicism for
the 21st century. Dev Dynam 219:19
Gilbert SF, Opitz JM, Raff RA (1996) Resynthesizing evolutionary
and developmental biology. Dev Biol 173:357372
Gottlieb G (1992) Individual development and evolution: the genesis
of novel behavior. Oxford University Press, Oxford
Hall B (2000) Evo-devo or devo-evodoes it matter? Evol Dev
2:177178
Hamburger V (1980) Embryology and the modern synthesis in
evolutionary theory. In: Mayr E, Provine W (eds) The evolu-
tionary synthesis: perspectives on the unification of biology.
Cambridge University Press, New York, pp 97112
Hamburger V (1988) The heritage of experimental embryology: Hans
Spemann and the organizer. Oxford University Press, Oxford
Hooker C (2011) Philosophy of complex systems. North Holland
Elsevier, Amsterdam
Huang S (2000) The practical problems of post-genomic biology. Nat
Biotechnol 18:471472
Kauffman SA (1993) The origins of order. Oxford University Press,
Oxford
Kim J (1998) Mind in a physical world. MIT Press, Cambridge
Klister M (2010) Causation across levels, constitution, and constraint.
In: Suarez M, Dorato M, Redei M (eds) EPSA Philosophical
issues in the sciences. Springer, Berlin, pp 141151
Laland KN, Odling-Smee J, Gilbert SF (2008) EvoDevo and niche-
construction: building bridges. J Exp Biol Mol Dev Evol
310B:118
Laland KN, Sterelny K, Odling-Smee J et al (2011) Cause and effect
in biology revisited: is Mayrs proximate-ultimate dichotomy
still useful? Science 334:15121516
Laland KN, Odling-Smee J, Hoppitt WJE et al (2013) More on how
and why: cause and effect in biology revisited. Biol Philos
28:719745
Laubichler MD, Maienschein J (2007) Embryos, cells, and organisms:
reflections on the history of evolutionary developmental biology.
In: Sansom R, Brandon RN (eds) Integrating evolution and
development. MIT Press, Cambridge, pp 124
Lee D, Severin K, Gadhiri M (1997) Autocatalytic networks: the
transition from molecular self-replication to molecular ecosys-
tems. Curr Opin Chem Biol 1:491966
Levin M (2012) Morphogenetic fields in embryogenesis, regeneration,
and cancer: non-local control of complex patterning. BioSystems
109:243261
Levins R, Lewontin RC (1985) The dialectical biologist. Harvard
University Press, Cambridge
Love A (2003) Evolutionary morphology, innovation, and the
synthesis of evolutionary and developmental Biology. Biol
Philos 18:309345
Love A (2006) Evolutionary morphology and evo-devo: hierarchy
and novelty. Theory Biosci 124:317333
Martnez M (2011) EvoDevo, complexity and multilevel causation.
In: Martnez-Contreras J, Ponce A (eds) Darwins evolving
legacy. Siglo XXI, Mexico City
Martnez M, Moya A (2011) Natural selection and multi-level
causation. Philos Theory Biol 3:e202
Mayr E (1961) Cause and effect in biology. Science 134:15011506
Merhej V, Raoult D (2012) Rhizome of life, catastrophes, sequence
exchanges, gene creations, and giant viruses: how microbial
genomics challenges Darwin. Front Cell Infect Microbiol 2:113
Mesoudi A, Blanchet S, Charmantier A et al (2013) Is non-genetic
inheritance just a proximate mechanism? A corroboration of the
extended evolutionary synthesis. Biol Theory 7:189195. doi:10.
3389/fcimb.2012.00113
Mitchell SD (2009) Unsimple truths: science, complexity, and policy.University of Chicago Press, Chicago
Miyakawa H, Imai M, Sugimoto N et al (2010) Gene up-regulation in
response to predator kairomones in the water flea, Daphnia
pulex. Dev Biol 10:45
Moreno A, Umerez J (2000) Downward causation at the core of living
organization. In: Andersen PB, Emmeche C, Finnemann NO et al
(eds) Downward causation. Aarhus University Press, Aarhus
Muller GB (2005) Evolutionary developmental biology. In: Wuketits
FM, Ayala FJ (eds) Handbook of evolution. Wiley, Weinheim,
pp 87115
Muller GB (2007) Six memos for evo-devo. In: Laubichler MD,
Maienschein J (eds) From embryology to evo-devo. MIT Press,
Cambridge, pp 459524
Muller GB, Newman SA (2003) Origination of organismal form: the
forgotten cause in evolutionary theory. In: Muller GB, Newman SA
(eds) Origination of organismal form. MIT Press, Cambridge, pp 310
Muller GB, Olsson L (2003) Epigenesis and epigenetics. In: Hall BK,
Olson W (eds) Keywords and concepts in evolutionary devel-
opmental biology. Harvard University Press, Cambridge,
pp 114123
Newman SA (2003a) From physics to development: the evolution of
morphogenetic mechanisms. In: Muller GB, Newman SA (eds)
Origination of organismal form. MIT Press, Cambridge,
pp 221239
Newman SA (2003b) Hierarchy. In: Hall BK, Olson W (eds) Keywords
and concepts in evolutionary developmental biology. Harvard
University Press, Cambridge, pp 169174
Newman SA, Forgacs G, Muller G (2006) Before programs: the physical
origination of multicellular forms. Int J Dev Biol 50:289299
Noble D (2006) The music of life: biology beyond genes. Oxford
University Press, Oxford
Noble D (2013) Physiology is rocking the foundations of evolutionary
biology. Exp Physiol 98:12351243
Odling-Smee FJ, Laland KN, Feldman MW (2003) Niche construc-
tion: the neglected process in evolution. Princeton University
Press, Princeton
Olsson L, Levit GS, Hofeld U (2010) Evolutionary developmental
biology: its concepts and history with a focus on Russian and
German contributions. Naturwissenschaften 97:951969
Multilevel Causation and the Extended Synthesis 219
123
-
Palsson B (2006) Systems biology: properties of reconstructed
networks. Cambridge University Press, Cambridge
Passera L, Roncin E, Kaufmann B et al (1996) Increased soldier
production in ant colonies exposed to intraspecific competition.
Nature 379:630631
Pigliucci M, Muller GB (eds) (2010) Evolution: the extended
synthesis. MIT Press, Cambridge
Plutynski A (2008) Explaining how and explaining why: develop-
mental and evolutionary explanations of dominance. Biol Philos
23:363381
Raoult D, Koonin EV (2012) Microbial genomics challenge Darwin.
Front Cell Infect Microbiol 2:127
Reif WE, Junker T, Hofeld U (2000) The synthetic theory of
evolution: general problems and the German contribution to the
synthesis. Theory Biosci 119:4191
Riedl R (2005) A systems theory of evolution. In: Hosle V, Illies C
(eds) Darwinism and philosophy. University of Notre Dame
Press, Notre Dame, pp 121143
Sepkoski D (2008) Macroevolution. In: Ruse M (ed) Oxford
handbook of philosophy of biology. Oxford University Press,
Oxford, pp 211237
Soto A, Sonnenschein C (2005) Emergentism as a default: cancer as a
problem of tissue organization. J Biosci 30:103118
Spemann H (1919) Experimentelle forschungen zum determinations-
und individualitatsproblem. Naturwissenschaften 7:581591
Strohman RC (2000) Organization becomes cause in the matter. Nat
Biotechnol 18:575576
Thierry B (2005) Integrating proximate and ultimate causation: just
one more go! Curr Sci 89:11801184
Trewavas A (2006) A brief history of systems biology. Plant Cell
18:24202430
van Der Weele C (1999) Images of development: environmental
causes in ontogeny. SUNY Press, Albany
Vrba E, Eldredge N (1984) Individuals, hierarchies and processes:
towards a more complete evolutionary theory. Paleobiology
10:146171
Weider LJ, Pijanowska J (1993) Plasticity of Daphnia life histories in
response to chemical cues from predators. Oikos 67:385392
West-Eberhard MJ (2003) Developmental plasticity and evolution.
Oxford University Press, New York
West-Eberhard MJ (2005) Developmental plasticity and the origins of
species differences. Proc Natl Acad Sci USA 102:65436549
Woodger JH (1929) Biological principles: a critical study. Kegan
Paul, Trench, Trubner, London
220 M. Martnez, M. Esposito
123
Multilevel Causation and the Extended SynthesisAbstractRethinking Causation in the Extended SynthesisThe Proximate/Ultimate Causal DichotomyThe Incompleteness of the Bottom-up Approach
Multilevel CausationThe Concept of Multilevel CausationNiche Construction and Multilevel CausationAutocatalytic Networks and Multilevel CausationNatural Selection and Multilevel CausationOntogeny and Multilevel CausationCarcinogenesis and Multilevel CausationPhenotypic Plasticity, Environment, and OntogenyAnimal Regeneration and Morphogenetic Fields
ConclusionsAcknowledgmentsReferences