## 1. Evolution and development in historical context



Originally, the concepts of evolution and development were closely
connected. In fact, since the end of the 17th century the
concept of 'evolution' was widely used to describe
individual developmental processes, and 'developmental
hypotheses' often referred to what is now called evolution. In
addition, development ('Entwicklung') was often considered
to not only describe ontogenetic changes in organisms (Goethe 1790;
Debraw 1777) but also (what we consider today) phylogenetic changes.
For example, Friedrich W.J. Schelling (1798) states that the sequence
of stages of all organic beings took shape through the gradual
development ('Entwicklung') of the same organization. This
situation changed in the beginning of the 19th century when
evolution was used by some authors for labeling transgenerational
transformations of organisms, among others by Charles Lyell and Georg
W.F. Hegel. However, in his first edition of his *Origin of
Species* (1859) Darwin did not use the term evolution, likely
because he wanted to distance his theory from earlier developmental
understandings of the word. Instead, he spoke of 'descent with
modification.' But especially due to the work of Herbert
Spencer, evolution became established as a concept that concerns the
"transformation of species", and Darwin's theory of
transformation through selection was increasingly seen as the exemplar
of a "theory of evolution" (Spencer 1852 [1891], 1).
According to this theory, evolution is driven through organisms
"struggle for existence" (Darwin) and the "survival
of the fittest" (Spencer).



Besides this increasing conceptual parting, however, evolution and
development were considered to be closely interrelated processes by
many scholars throughout the 19th century. By building on
earlier comparative studies of embryonic processes across various taxa
(among others by Karl E. von Baer (1827) and Fritz Muller
(1864)), Ernst Haeckel (1872) argued that all metazoans have the same
early stages of development (see Gould 1977). He understood these
developmental patterns as modifications of a basic type. According to
this biogenetic law, the development of individuals is a
recapitulation of species' evolutionary changes:



> 
> 
> During the rapid and short course of its individual development, the
> organic individual [...] repeats the most important changes of
> form, which its ancestors passed through during their long and slow
> course of paleontological development, following the laws of heredity
> and adaptation. (Haeckel 1866, II 300)
> 
> 
> 



This relationship, whereby biodiversity progressively arose from
changes in development, was already anticipated by Johann F. Meckel
(1812) and Richard Owen (1837), who parallelized
'transmutations' of embryonic forms and transmutations of
species. Also Darwin (1837) describes the genesis of individuals as a
'shortened repetition' of morphological changes during
phylogeny. From the end of the 19th century this view of
development as a recapitulation of evolution became problematic (see
Rasmussen 1991). First, during this time the view of a linear
evolution from invertebrates over vertebrates to humans was
increasingly questioned. Second, based on comparative studies of cell
lineages across different taxa in the 1890s, scholars criticized that
not only adult organisms but their developmental pathways evolve, too.
For example, in 1898, embryologist Edmund B. Wilson (1898) was using
homologous patterns of embryonic cell division to unite taxa, while
embryologist Frank R. Lillie (1898) studied differences in these
patterns to show the origins of evolutionary adaptations. These
studies were (at least to some part) in conflict with Haeckel's
recapitulationism, as they saw ontogeny not as sufficiently explained
by historical causes, but rather in need of independent mechanistic
laws operating on physical properties of the ontogenetic material (see
Guralnick 2002). In addition, this cell lineage research suggested
that Haeckel's law on the relationship between development and
evolution should be inverted, as cell lineages evolve over
evolutionary time. In more general terms, this means that development
does not merely mimic evolution. Rather, it is a source of variation
and thus a cause of evolution and adaptation: "ontogeny does not
recapitulate phylogeny, it creates it" (Garstang 1922: 81). In
short, evolution proceeds through modifications of development.



Another characteristic of 19th century (and early
20th century) biology was the lack of a clear conceptual
parting between developmental and reproductive processes. Especially
the idea of the inheritance of acquired characteristics was part of
the mainstream of evolutionary thought (Bowler 1983, 2017; Gissis
& Jablonka 2011). According to Jean Baptiste Lamarck (1809),
changes in the structure or function of traits that occurred during an
organism's life, depending on their use or disuse, could be
inherited. Darwin adopted this idea in his inheritance theory of
pangenesis (see Holterhoff 2014). He suggested that all body parts, at
each developmental stage, contain small particles, so-called
'gemmules,' that were sensitive to environmental changes.
These particles accumulate in the reproductive organs and are
transmitted to the next generation. Thus, gemmules modified during
development lead to modifications in the next generation. Darwin
stated that due to this close connection of development and
reproduction, "inheritance must be looked at as merely a form of
growth" (Darwin 1868: II, 404). However, this connection between
development and inheritance was increasingly criticized in the first
half of the 20th century. Following August Weismann (1892),
the inheritance of environmentally induced variation in somatic cells
(the body) of organisms was increasingly called into question. In
sexually reproducing organisms, only the germ plasm used for the sperm
and eggs were recognized as carrying information that are passed on to
the next generation. According to this view, the germ line was immune
from variation occurring in the somatic cells of the body, and thus
the inheritance of acquired characteristics or other theories of
plasmatic inheritance were rejected (but see Harwood 1993, Gilbert
& Epel 2015). 



This parting between development, on the one side, and inheritance and
evolution, on the other, through Weismann's theory of
inheritance, had long lasting effects on how biologists reasoned about
evolution in the following years. Despite continuing efforts of
neo-Lamarckians well into the 1930s (Bowler 1983), development
increasingly vanished from the landscape of evolutionary theory. By
uniting Mendel's laws and new findings in genetics within the
statistical framework of population genetics, the modern synthesis
came to understand evolution as a change in the frequencies of
different alleles in a population (Fisher 1930; Dobzhansky 1951).
Variation relevant to evolution was produced only in the genes of the
germ line. These random changes, mutations, were screened off from the
developmental history of the individual. In the 1940s and 50s this
view was increasingly manifested, not least through the so-called
'central dogma' of molecular biology (Crick 1958). It
states (similar to Weismann's theory) that information flows
always from the DNA to proteins, never vice versa. Thus, phenotypic
changes during development could not affect the genes. The trend to
link genes with populations in evolutionary explanations, rather than
development with evolution reached its climax with the gene's
eye view of evolution (Williams 1966; Dawkins 1976). By focusing on
the question how certain traits like altruistic behaviors could be
beneficial, it not only identified genes (rather than organisms) as
the sole units of selection. In addition, it described development as
nothing but the readout of a genetic program (Maienschein 2003;
Pigliucci 2010). Genes control the development of traits and
organisms' behaviors, and they replicate to secure their own
further propagation in groups and populations.



During the twentieth century these partings of development and
evolution led to statements such as: "Problems concerned with
the orderly development of the individual are unrelated to those of
the evolution of organisms through time" (Wallace 1986: 149).
However, such statements were also targeted by a number of critics.
For example, the exclusion of developmental biology from the modern
synthesis (Harrison 1937; De Beer 1954; Waddington 1957; Hamburger
1980), the explanatory autocracy of the adaptationist program in
evolutionary biology (Gould & Lewontin 1979), and the omission of
a satisfying theory of evolutionary novelty, in which development
would play a role (Goldschmidt 1940), have been criticized. Not least
due to this rejection of developmental perspectives, evolutionary
theory has been blamed to constrain the direction of research in
evolutionary biology (Provine 1989). In fact, throughout the twentieth
century a number of theories have been put forward, which argue that
due to the partial independence of genetic and phenotypic variation,
evolutionary research should put more emphasis on how the changes in
developmental and behavioral patterns might drive or bias evolutionary
change. This includes cases of 'canalized' developmental
pathway which are maintained, even though the genotype or the
environment might have changed to some degree (Waddington 1957; see
also Nijhout 2002; Gilbert & Epel 2015; Sultan 2015). In addition,
studies of phenotypic plasticity showed that a trait of an organism
can react to an environmental input in various ways, and that the
genome codes for a wide range of potential phenotypes (Waddington
1942; Nijhout 1990; Pigliucci 2001). The evolutionary relevance of
these findings was emphasized by studies that investigated how the
range of variation changes from a plastic trait to a fixed or
canalized one over the course of generations (Suzuki and Nijhout 2008;
West-Eberhard 2003; B. Baker et al. 2019). What is more, according to
the so-called 'Baldwin effect,' learned behavioral
patterns (e.g., the acclimatization to a new stressor) that were
initially rather plastic, can affect the reproductive success of
individuals and thus, across generations and through natural
selection, be gradually incorporated into the genetic and epigenetic
makeup of a species (Baldwin 1896; Simpson 1953; Piaget 1976 [1978];
Newman 2002). While some of these developmental perspectives on
evolution were consistent with the population genetic framework of
evolutionary biology and were, in fact, gradually incorporated into
evolutionary thought, others posed more serious challenges for
theoretical integration.



By building on the latter, more problematic set of approaches
(especially in recent years), evolutionary theory has been facing
calls from developmentally oriented biologists and philosophers of
biology to widen the standard explanatory and methodological
approaches on evolution (Bonner 1958; Alberch 1982; Bonner 1982; Raff
& Kaufman 1983; Gilbert, Opitz, & Raff 1996; Schlichting &
Pigliucci 1998; West-Eberhard 2003; G. Muller 2007; Pigliucci
& Muller 2010; Bateson & Gluckman 2011; Jablonka &
Lamb 2014; Laland et al. 2014, 2015; Gilbert & Epel 2015; G. Muller 2017; for discussion, see Huneman
& Walsh 2017; Fabregas-Tejeda & Vergara-Silva 2018; Baedke et al. 2020b). They argue that evolutionary change should not only or
primarily be investigated and explained as a change in genotype
frequencies in populations but (also) on the level of the developing
and acting individual. The underlying idea is that phenotypic
variation and the flexibility of organisms' responses to
environmental cues may introduce non-random variation and thus may
bias and/or direct morphological evolution to some degree. This
includes not only environmentally induced changes in regulatory
processes but also the physical constraints of the developing embryo.
By focusing on these phenomena, Kevin Laland and colleagues (2014:
161) state: "An alternative vision of evolution is beginning to
crystallize, in which the processes by which organisms grow and
develop are recognized as causes of evolution". Others have
argued that genes are probably more often followers in evolution than
leaders (West-Eberhard 2003, 2005). In other words, the
environmentally responsive, developing and acting organism takes the
lead. It introduces in a non-random way new phenotypes into
populations that are subsequently stabilized by genes.



This 'development first view' (or sometimes called
'plasticity first view') of evolution is currently adopted
especially by researchers in three fields of research: evolutionary
developmental biology (evo-devo), epigenetics, and niche construction
theory. Evo-devo studies how developmental pathways evolve and, more
important for the above view, how developmental constraints and biases
can affect evolutionary trajectories (Raff 1996, 2000; Gerhart &
Kirschner 1997; Love 2003; Amundson 2005; Laubichler & Maienschein
2007; Sansom & Brandon 2007; G. Muller 2007; Minelli 2009;
Laubichler 2010; Pigliucci & Muller 2010; Gilbert & Epel
2015; Moczek et al. 2015; Levis & Pfennig 2020). This includes
asking how changes in gene regulatory networks cause modifications of
developmental processes (associated with major shifts in morphological
'body plans') and thus produce evolutionary novelties, or
what capacities organisms have to generate heritable, adaptive
phenotypic variation and thus to evolve in evolution (i.e. their
evolvability; see Hendrikse et al. 2007). This focus on how phenotypic
variation is produced, rather than how it is selected, is supported by
studies in epigenetics on inter- and transgenerational epigenetic
inheritance (see the entry
 inheritance systems),
 like through the transmission of regulatory factors of gene activity
(Jablonka & Lamb 1989, 2014, Janlonka & Raz 2009, Perez &
Lehner 2019). Other forms of extra-genetic inheritance include the
transmission of microbiota (Gilbert et al. 2012, 2014, Browne et al.
2017) and behaviorally mediated parental effects (Kappeler &
Meaney 2010; Rilling & Young 2014). This set of processes contains
environmentally sensitive non-genetic sources of variation for
organisms that can be transmitted across generations, in many cases
decoupled from the transfer of genetic information. Finally, niche
construction theory highlights the self-perpetuating and reciprocal
effects of organisms, as agents, that construct their own niche
(and/or that of other species) during development (Lewontin 1982;
Sterelny 2001; Day et al. 2003; Odling-Smee et al. 2003; Laland et al.
2008, 2009, 2011; Odling-Smee 2010; Chiu & Gilbert 2015, 2020; Aaby & Ramsey forthcoming).
These recent studies on developmental evolution will be discussed in
detail in section 3.



The various developments in the above fields have led to an increasing
philosophical interest in conceptual and explanatory issues arising
from the new junction of development and evolution. These include
clarifying what causal relationships and boundaries exist between the
two realms, which different roles developmental processes play in
recent evolutionary research, and how these new roles affect
ontological frameworks of the organism. In addition, these
developments have been accompanied by debates about the structure of
explanations in developmental evolution. Finally, they have informed
discussions on anthropological understandings and ethical questions
concerning humans. We will now discuss the debates on these issues in
detail. 


## 2. Conceptual partings and unifications of evolution and development



One of the most central topics of early philosophy of biology in the
1960s and 1970s was the attempt to develop a suitable conceptual
framework that would support the parting between development and
evolution in line with the central assumption of the Modern Synthesis
that evolution is a change in the genetic composition of populations
only (Dobzhansky 1951: 16; see also Charlesworth et al. 2017). This
means, as a consequence, that development does not (or not in
significant ways) causally effect evolution. Over the decades this
assumption has been supported by the historically influential
conceptual distinction between proximate causes and ultimate causes
(Mayr 1961).


### 2.1 The proximate-ultimate distinction



The dual framework 'proximate vs. ultimate' provides a
qualitative distinction of biological causality (for related
distinctions, see J. Baker 1938; Tinbergen 1951, 1963). It holds that
biologists who study proximate causes ask how questions about
individual developmental processes. Thus, functional biologists
interested in such proximate causes study how systems work. Instead,
evolutionary biologists that study ultimate causes ask why questions,
like why phylogenesis has produced particular evolutionary functions.
According to this distinction, at least on the surface, proximate
causes resemble Aristotelian efficient causes while ultimate causes
resemble Aristotelian final causes. To illustrate this distinction,
Mayr (1961) draws on an example of avian migration. Migration can be
studied by asking how bird migrate (i.e., how they develop skills like
navigation) or why they migrate (i.e., due to what selective
advantage). These two investigations are understood to be both
important and complementary. However, they should be treated as
distinct from one another.



The proximate-ultimate distinction can be given an epistemic or
ontological reading. First, authors have interpreted it as
distinguishing different kinds of explanations (Amundson 2005; Calcott
2013; Scholl & Pigliucci 2015). This epistemic reading includes
that how questions cannot be addressed by explanations citing ultimate
causes (i.e., telling a story of adaptation) and that why questions
cannot be addressed by explanations citing proximate causes (i.e.,
telling a story of trait development). Second, authors have
interpreted this distinction as one between different ontological
classes of causes working in ontogenetic and phylogenetic processes
(Laland et al. 2013a). This ontological reading is backed up
theoretically by Weismann's concept of the separation of germ
line and soma, which provides a demarcation line between two distinct
classes of causes. To this day, biologists and philosophers have not
reached a consensus on how exactly the division
'proximate-ultimate' or 'how-why' should be
understood, epistemically or ontologically (Francis 1990; Dewsbury
1992, 1999; Sterelny 1992; Beatty 1994; Ariew 2003). Despite this lack
of agreement this framework has been applied in various fields, from
evolutionary biology (E. O. Wilson 1975 [2000: 23]), evolutionary
psychology (Daly & Wilson 1978; Crawford 1998) and behavioral
ecology (Morse 1980: 92-95) to human sciences, like in human
cooperation (Marchionni & Vromen 2009) and developmental
psychology (Lickliter & Berry 1990). Especially in evolutionary
biology it has contributed to mainstream causal reasoning for a long
time, even among evolutionary biologists interested in developmental
processes (see, e.g., Maynard Smith 1982: 6).


### 2.2 The integration of proximate and ultimate causes



There has been constant criticism of the proximate-ultimate
distinction (since even before Mayr 1961), and against its underlying
idea to downgrade the explanatory or causal relevance of development
to evolution. More recently, the discussion of this issue gained pace
through new findings in fields such as epigenetics, evo-devo and niche
construction theory (Thierry 2005; Laland et al. 2011, 2013a, 2013b;
Haig 2011, 2013; Scott-Phillips et al. 2011; Dickins & Rahman
2012; Guerrero-Bosagna 2012; Calcott 2013; Dickins & Barton 2013;
Gardner 2013; Mesoudi et al. 2013; Martinez & Esposito
2014; Scholl & Pigliucci 2015; Baedke 2018; Uller & Laland
2019). In this context, some scholars argue that the
proximate-ultimate distinction stands "at the center of some of
contemporary biology's fiercest debates" (Laland et al.
2011: 1512) about the role of developmental plasticity, niche
construction and inclusive inheritance for evolutionary trajectories.
Participants in this debate have argued that we should, due to
different epistemic or heuristic reasons, keep Mayr's
proximate-ultimate distinction (Scott-Phillips et al. 2011; Dickins
& Barton 2013) or a revised or reinterpreted form of it (Scholl
& Pigliucci 2015; Otsuka 2015), expand it by a third intermediate
form of explanations (Haig 2013), or replace it with a concept of
'reciprocal causation' (Laland et al. 2011, 2013a, 2013b,
2015; Mesoudi et al. 2013). In line with earlier philosophical work
(Oyama 1985; Keller 2010; Griffiths & Stotz 2013), the latter idea
of reciprocal causation should allow describing the feedback processes
between causal factors in evolving systems. This includes
organisms' capacity of phenotypic plasticity or, more
specifically, their activities to alter selection pressures.
Paradigmatic feedback cases are niche construction behaviors of
organisms that modify their environments and thus shape natural
selection pressures working on them. In other words, reciprocal
causation holds that organisms are not only effects of adaptive
processes, but also causal starting points of evolutionary
trajectories. In this sense this framework argues against the causal
and/or explanatory asymmetry claim of the proximate-ultimate
distinction. It highlights the important role of development for
evolution.



Against this new approach, scholars have argued that reciprocal
causation does, in fact, not pose any conceptual challenges for
evolutionary biology, as it has been included since quite some time
ago in the field (Svennson 2018). A true challenge, however, is to
develop this idea into a methodologically sound framework that allows
studying and modeling complex non-linear organism-environment
relations. Other have cast doubt on the central causal role the unit
of the organism is supposed to play in this reciprocity framework
(Baedke 2019a), or questioned whether this conceptualization can, in
fact, capture all causal dependency relations of interest for
evolutionary biology (Martinez & Esposito 2014; Scholl
& Pigliucci 2015). Moreover, some argued that also this framework
relies on the dichotomy between development and evolution (Dickins
& Barton 2013; Martinez & Esposito 2014) and that it is not conducive to
successful biological science, as it does not lead to falsifiable
questions (Dickins & Rahman 2012) and bleeds proximate and
ultimate explanations into each other so that their distinction
becomes meaningless (Gardner 2013; one should mention, however, that
this might be the very aim of this approach). More generally, it has
been requested that advocates of this approach should provide more
conceptual clarifications on what reciprocal causation actually is
supposed to mean (Buskell 2019).



Besides distinguishing development and evolution in a qualitative
manner as proximate and ultimate causal processes, a less common
attempt is to quantitatively distinguish (or relate) the two. Here,
especially distinctions based on the rates or time scales on which
different developmental and biological processes occur have been made
(see the entry
 levels of organization in biology).
 For example, Conrad H. Waddington (1957) developed a hierarchical
model of time scales that includes biochemical processes on lower
molecular levels of organization with a faster rate, medium paced
processes of development on a medium level, and evolutionary processes
on higher levels with a slower rate. According to such a view,
evolutionary processes are simply processes occurring with a different
rate and thus at a different level than developmental ones. Thus, they
differ gradually rather than in kind. Rate-based distinctions have
been described to be consistent with the ultimate-proximate framework
(when interpreting it as one that distinguishes different timescales
of phenotypic change; see Francis 1990; Haig 2013) or as different
from proximate-ultimate distinctions (Baedke & Mc Manus 2018). In
addition, time-scale (or size-scale) conceptualizations have been
applied for developing methodologies and multi-scale modeling that
integrate, among others, developmental and evolutionary processes (S.
Levin 1992; Green & Batterman 2017; Duckworth 2019).


## 3. Developmental change as the mechanism for evolution



The idea that evolution constitutes changing developmental
relationships is central for the field of evolutionary developmental
biology (evo-devo). The field describes itself as the science that
studies how alterations in development create the variations that
nature can select (Raff & Kaufman 1983; Gilbert, Opitz, & Raff
1996). In other words, natural selection did not create variation;
development creates variation. Development is the artist; natural
selection is the curator (Gilbert 2006, 2019). Both have creative
agency; but they are working at different levels. Although this view
had been expressed by scientists such as Thomas Huxley, Julian Huxley,
Conrad H. Waddington, and Richard B. Goldschmidt, it gained credence
through more recent discoveries that explained how normal development
could occur. Chief among these discoveries was the explication of
developmental pathways that connected embryonic induction with gene
expression. Here, paracrine factors (proteins that influence the
behaviors or gene expression patterns of neighboring cells) secreted
by one set of cells were received by receptors on the membranes of
other cells. These receptors then activated proteins within the
cytoplasm, which eventually activated or repressed proteins that entered
the nucleus to regulate transcription of particular genes.



The second major discovery that promoted evo-devo was the discovery of
modular enhancers. The above-mentioned transcription factors would
bind to specific regions of DNA, called enhancers. Most genes have
multiple enhancers. Thus, a gene might have a 'limb'
enhancer that activates the expression of the gene in the limb, and an
'eye' enhancer that enables the expression of the gene in
the eye. Moreover, each enhancer usually binds several transcription
factors and could be activated in Boolean <and> or <or>
fashion. Evolution could occur by creating or deleting enhancers,
thereby enabling genes to be expressed differently in different
species. King and Wilson (1975) and Jacob (1977) had speculated that
evolution occurred by changes in gene regulation. This provided a
model for such regulation, and some of the best examples are seen in
the divergence of humans from other apes (Geschwind & Konopka
2012; Pollard et al. 2006). As Haraway (2008) noted, "relationships are the smallest
possible pattern for analysis", and the relation between
enhancer and transcription factor may indicate the 'natural
kinds' of the biological world (Gilbert & Bard 2014).
Moreover, the entities defined by enhancer/transcription factor
interactions during development are often unexpected and do not mirror
intuitive boundaries between entities in adults. Activation of genes
to form the distal rib, for instance, is controlled by a different
enhancer than that which activates genes in the proximal rib (Guenther
et al. 2008).



These differences in gene expression could be categorized into four
categories (Arthur 2004). One of these categories involves the
*place* of gene expression, where different populations of
cells express a particular gene in different species. For instance,
the *gremlin* gene in the duck hindlimb webbing protects these
cells from cell death, enabling webbed feet (Laufer et al, 1997;
Merino et al. 1999). A second category involves changes in the
*timing* of gene expression, as in the continued expression of
the *fgf8* gene at the tip of the dolphin forelimbs, thus
enabling the extension of its flippers (Richardson &
Oelschlager 2002). A third category of change involves
alterations in the *magnitude* of gene expression, as in the
differences in *Bmp4* gene expression that determine the width
of finch beaks (Abzhanov et al. 2004). A fourth category focuses on
the alterations of the actual *protein sequence* of regulatory
proteins, as in the changes of the *Antennapedia* gene in
insects, which restrict insects from forming more than six limbs
(Galant and Carroll 2002).



The third discovery was the elucidation of gene regulatory networks
(GRNs). A GRN is based on paracrine factors, signal transduction
cascades, and transcription factors. While ignoring
post-transcriptional gene regulation, this concept attempts to explain
how initial conditions (RNAs and proteins within the oocyte, position
of the embryo within the uterus, etc.) could create the conditions
whereby cell types differ, even though their genomes are identical.
Spearheaded by Eric Davidson (2001, 2006), this approach uses systems
theory concepts such as modularity and dissociability to explain how
the genes interact in a hierarchical manner to produce different
cell types (Levine & Davidson 2005) and how the cell types in
related species could differ by the recruitment (co-option) of a
particular GRN by altering transcription factor binding. More
generally, the discovery of GRNs has enabled the integration of
developmental biology with paleontology (Jablonski 2017; Hinman et al.
2003; Hinman & Cheatle Jarvela 2014) and may also be extended into
areas of symbiosis and niche construction (Laubichler & Renn
2015).



A fourth discovery of evolutionary developmental biology was the
importance of developmental plasticity for evolution (Nijhout 1990;
Gilbert 2001; Pigliucci 2001). By the end of the 20th century, the
roles of temperature, sunlight, diet, crowding, maternal behaviors,
and predation were seen to have major roles in effecting phenotypes in
plants and animals. Thus, the environment not only selected
variations, it helped produce them. Since evo-devo postulated that
changes in development cause evolution, and since developmental
plasticity played a role in development, then it became necessary to
look at changes in plasticity as being part of evolution. In the early
years of the 21st century, developmental plasticity was seen to play
roles in evolutionary change (West-Eberhard 2003; Abouheif et al.
2014; Suzuki & Nijhout 2006; Rajakumar et al. 2018; Levis &
Pfennig 2020), and the notion of 'plasticity-first
evolution' (or 'development-first evolution')
integrated data from numerous sources into a program where the
physiological ability to alter one's phenotype due to
environmental agents could become canalized and genetically fixed by
selection. The mechanisms by which such plasticity-first evolution was
effected (unmasking and selection of cryptic genetic variants,
stress-related inability of molecular chaperones to allow proper
folding of mutant proteins, etc.) became a new research program.



A fifth discovery was the realization that one of the major
environmental agents effecting development were symbiotic microbes
(McFall-Ngai 2002; Gilbert et al. 2012, 2015). The notion of the
holobiont (i.e. an integrated composite organism composed of microbial
and host eukaryotic species) organized much of the data to look at the
roles of microbes in causing both the normal development of the
organism and variations of normal development (in disease and
evolution) (Rosenberg & Zilber-Rosenberg 2016; see entry
 biological individuals).
 For instance, in the mouse, the normal development of the immune
system and the gut capillary network depends upon specific bacteria
obtained during birth. These bacteria induce the expression of
particular genes in the eukaryotic cells, and the proteins made by
these genes influence cell fate (Hooper et al. 2001; McFall-Ngai et
al. 2013). In other words, the bacteria can act as an embryonic cell
would, regulating gene expression in neighboring cells. Here, the
eukaryotic organism needs and expects these bacteria to be present for
normal development.



As in the other cases of developmental plasticity, the next step was
to see if changes in developmental symbionts could produce changes in
evolution (see O'Malley 2015). It was shown that changes in symbionts could provide
selectable variants for evolution (Zhang et al. 2019), and it could
provide the basis for reproductive isolation through cytoplasmic
incompatibility or mating preference (Brucker & Bordenstein 2013;
Sharon et al. 2010). One of the most interesting possibilities,
though, comes from the view that most, if not all, eukaryotic
organisms are holobionts, and that symbionts open new evolutionary
trajectories. Symbiotic microbes, for instance, have long been known
to be responsible for the plant-digesting enzymes in the stomachs of
ruminants. Without cellulose-digesting bacteria, cows cannot digest
grass or grain. Moreover, the microbes help create the rumen after
they colonize the digestive system at birth. Thus, these microbes also
induce the formation of the organ that houses them, and allows them to
function (Gilbert 2020; Chiu & Gilbert 2020). Developmental
symbiosis (sympoiesis) thus has opened evolutionary trajectories for
certain mammals. This is an example of both developmental symbiosis
and niche construction. Niche construction depends on developmental
plasticity (Laland et al. 2008).



These five new (or renewed) aspects of developmental biology have
several philosophical implications. Among others, they concern
ontological questions of what developing organisms are and how they
should be explained from an integrated perspective of developmental
evolution.


## 4. Ontological challenges of developmental evolution



Many ontological debates on the relation between development and
evolution focus on the organism as the central unit, which both
develops and evolves, in contrast to, for example, genes or
populations. Several theories have tried to clarify the nature of this
organismic unit: According to one influential view, the organism is a
series of integrated processes during a life cycle (Bonner 1965;
Nicholson & Dupre 2018; Fusco 2019a; DiFrisco 2019), with
complex and reciprocal relationships between the whole organism and
its parts (Gilbert & Sarkar 2000; Esposito 2016; Peterson 2017).
Central elements of this view are based on an organicist framework
developed by Kant, which states that in organisms "the parts,
with respect to both form and being, are only possible through their
relationship to the whole" and "that the parts bind
themselves mutually into the unity of a whole in such a way that they
are mutually cause and effect of one another" (Kant 1790/1793
[1902: 373]; see also Lenoir 1982). Haraway (2008) highlights the
latter idea of reciprocal interaction between organisms' parts
by saying: "Reciprocal induction is the name of the game"
(2008: 228) and it is "reciprocating complexity all the way
down" (2008: 42).


These ideas of life cycle integration and
ubiquitous reciprocity suggest a more processual and organism-centered
ontological perspective on the organism. This view is becoming
important in studies of evolution. For example, in order to understand
how nervous systems evolve one need to consider that the nervous
system of the developing organism has different functions than the
adult nervous system and may be used to coordinate body construction
as it develops (M. Levin 2019; Fields et al. 2020). That developing
systems show exaptation and competition and that evolving systems show
cooperation has allowed Fields and Levin (forthcoming) to suggest that
developmental and evolutionary processes can be integrated on a
scale-free level through the language of information processing and
communication.



A second ontological consideration states that developing and evolving
organisms are integrated collective individuals, so-called holobionts
or 'meta-organisms' (Zilber-Rosenberg & Rosenberg
2008; Bosch & McFall-Ngai 2011; Gilbert, Sapp, & Tauber 2012;
see also O'Malley 2017; Baedke et al. 2020a). Therefore, our
discussions about evolution must take into consideration that each
organism is a consortium having numerous genomes, not just one, as
traditionally assumed. Mathematical modeling of the evolution of
holobionts that take this diversity into consideration is just
beginning (Roughgarden et al. 2018; Osmanovic et al. 2018; Roughgarden
2020). This new ontological framework states that symbiosis is the
norm; it is not peripheral. These symbionts can act at different
stages of the life cycle and are seen to scaffold development
(Griesemer 2014; Chiu & Gilbert 2015; Minelli 2016). In
'scaffolding,' each developmental stage is made possible
by entities and processes that catalyze these activities, which allows
novel and evolutionary relevant processes to occur at lower
difficulties and costs.



A third ontological point concerns the exact nature of the link
between development and evolution. Two approaches have been put
forward: One draws on the idea that the biological entity that is
causally efficacious in both realms can only be found on the level of
integrated collectives of symbiotic interactions. Following in the
tradition of Leibnitz' notion of compossibility as well as
Margulis' (1999) claim that we live on a 'symbiotic
planet,' this view argues that symbiotic collectives are not
only essential units of development but also of evolution. This leads
to a view of evolution that is not centered on interspecies conflict
and competition between individuals (Huxley 1888; Williams 1966;
Dawkins 1976). Instead the entities that evolve are cooperative
co-developing collectives (Rosenberg & Zilber-Rosenberg 2016;
Roughgarden et al. 2018; for discussion, see Peacock 2011;
Suarez 2018).



A different ontological framework links
development and evolution through the entity of the acting organism
(Nicholson 2014, 2018; Walsh 2015; for discussion, see Pradeu 2016;
Baedke 2019a, 2019b). These approaches usually are less related to
symbiosis research than to studies on niche construction or maternal
effects. Here the organism (e.g., a beaver that builds a dam or an
earthworm that processes the soil) is constructed as a self-determined
agent that through its behavior modulates the selection pressures
acting on it (Odling-Smee et al. 2003; Uller & Helantera
2019). Thus, so the argument goes, it can bias and direct population
dynamics. The holobiont perspective and the niche construction
perspective join together when one appreciates that the microbes and
the host form each other's environment. Here, the host and the
microbes scaffold each other's development and evolution (Chiu
& Gilbert 2015, 2020). 



Whether or not we consider collectives or organismic individual agents
as the core entities partaking both in development and evolution,
attempts to integrate the two realms have to show in each case that,
in fact, it is the same unit that develops *and* evolves. In
other words, if we want to unify development and evolution through the
unit of the biological individual (being the one entity that partakes
in both) this unit needs to meet criteria of both physiological (e.g.,
metabolic) and evolutionary individuality (see the entry on
 biological individuals).
Evolutionary individuals have been traditionally conceptualized as
reproductive units with differential fitness and shared lineages
(so-called 'Darwinian individuals'; see Godfrey-Smith
2009) or as units of selection ('interactors'; see Hull
1980). Unfortunately, both of these units do not always coincide
(Godfrey-Smith 2013; Pradeu 2016). For example, some organisms (holobionts) form developing
but no reproductive units, as they include a multitude of lineages
(e.g., microbial ones). Other possible units of selection (like genes
or populations) are not identical with physiological individuals.
Thus, a physiological individual may not necessarily be an
evolutionary unit or vice versa.



This brings us to a fourth ontological point: developmental
plasticity, which is considered to bias or even guide evolutionary
trajectories (West-Eberhard 2003; Radersma et al. forthcoming). The
concept of plasticity states that development can be regulated in
important ways by the environment. This rules out genetic determinism
(but not necessarily environmental determinism; see Waggoner and Uller
2015). In the original conception of phenotype production (i.e.,
development), Wilhelm Johannsen (1909) had pointed out that the phenotype
is the product of both the genotype and environmental circumstance, and
Woltereck (1909; see also Sarkar 1999) argued that what was inherited
is the "*Reaktionsnorm*", a potential to generate
phenotypic variations in response to environmental agents. In line with this view, many
embryology texts in the late 1800s (e.g., Hertwig 1894) had promulgated the
perspective that development demanded both the interactions between
embryonic cells and the further interactions of those cells with the
environment (see Nyhart 1995).



Despite this history, developmental plasticity was marginalized as
genetic explanations came to the fore in the mid-20th century (Sarkar
1998; Keller 2002). Against this background, embryologists such as
Lewis Wolpert (1994) could ask whether an organism's phenotype
could be computed if we had the total description of the egg. Due to
the above findings on organism-environment interaction (see section
3), a different view emerged that more seriously considers the
environmental-responsiveness and plasticity of the developing
phenotype. This view includes a shift from externalist to internalist
or constructionist understandings of the organism-environment
relationship (Godfrey-Smith 1996). While the externalist view -
the orthodox view in evolutionary theory - conceptualizes
properties of organisms as a result of their environments (i.e.
natural selection targeting genetic programs), the internalist view
sees "one set of organic properties in terms of other internal
or intrinsic properties of the organic system" (Godfrey-Smith
1996: 30). According to these two accounts, organisms occupy an
environment that covaries with them or that is largely independent of
their variation. The above research in developmental evolution
suggests a switch from an externalist to a constructionist
perspective, in which the organism actively molds its internal states
and responds to and alters its external environment (see Laland et al.
2014, 2015). In addition, in this framework also the causal role of
the environment becomes more complex. It now includes the idea that
the environment has active agency that can determine the phenotype.
Rather than conceptualizing the environment as nothing but a passive
filter for evolution, in this view the environment plays a role in
actuating the phenotype in addition to selecting it (Moczek 2015;
Gilbert & Epel 2015).


## 5. Explanations of developmental evolution



Besides these discussions about the ontology of developing and
evolving organisms, other central philosophical debates on the
interface between development and evolution have targeted the topic of
scientific explanation. This refers to the questions of what studies
of developmental evolution (should) explain and how they explain. 


### 5.1 Mechanistic explanations of developmental evolution



Philosophers of science have long argued for the explanatory autonomy
of biological explanations. Especially, they have criticized
understanding biological explanation as similar to law-based accounts
of explanations in physics (see Lange 2007). In contrast, scholars
have argued that explanation in the biosciences often includes
describing a mechanism that brings about a certain biological
phenomenon (Bechtel & Richardson 1993; Craver 2007; Bechtel &
Abrahamsen 2010; see also entry
 mechanisms in science).
 Especially evo-devo has been described as a paradigmatic mechanistic
science, which - against the ultimate-proximate distinction
- seeks to identify developmental mechanisms that can explain
evolutionary change in phenotypes (Gilbert 2003; Hall 2012). This
mechanistic approach is often flanked by mathematical models of
various developmental patterns, from changes in gene regulatory
networks to growth patterns of organisms, and by historical narratives
on how organisms and species evolve (Jaeger & Sharpe 2014; Winther
2015). However, besides the accepted centrality of mechanistic
explanation for developmental evolution, a much-debated topic concerns
what exactly a developmental mechanism is and how it functions in
evolutionary explanation compared to standard explanations citing
natural selection. 



Philosophers of biology (in the so-called new mechanistic philosophy)
have conceptualized mechanistic explanations in biology as the
construction of models of mechanisms that connect parts of systems,
located on one level of organization, with behaviors of the whole
system, usually located on a higher level of organization (Machamer et
al. 2000; Craver 2007; Illari & Williamson 2012). In this
framework, mechanistic models relate different compositional levels of
organization, like genes and phenotypes or cells and tissues. These
inter-level relations exist between causal capacities of parts of a
system and their organization and the capacities of a system as a
whole. Such relations are established following a procedure of
decomposition and localization (Bechtel & Richardson 1993; Craver
2007; Menzies 2012). This conceptual framework to describe biological
mechanisms and mechanistic explanation has been developed based on
case studies in molecular and cell biology. However, scholars have
cast doubt on whether it is also useful to describe mechanistic
explanations in studies of development and developmental
evolution.



With respect to development, it has been argued, first, that
organization plays a different role in mechanistic developmental
explanations (Mc Manus 2012). In contrast to the above framework,
which usually presupposes that levels of organization are simply
there, and thus it does not have to clarify how levels of organization
actually originate, the origin of levels and other forms of
organization (e.g., spatial axes) are specifically addressed in
mechanistic developmental explanations. Second, philosophers have
argued that the relations between levels traced by developmental
mechanisms are not exhausted by the synchronic, constitutive relations
between parts and wholes, as some new mechanists suggest (Craver &
Bechtel 2007). In contrast, developmental explanations trace changing
diachronic relationships between causal capacities of a system at
different levels of organization at different time intervals (Ylikoski
2013; Baedke & Mc Manus 2018; Baedke 2020; see also Love &
Huttemann 2011). Third, it has been argued that explanations in
evo-devo using developmental mechanisms face a challenge due to the
heterogeneity of these mechanisms (Love 2018). When trying to
integrate two types of explanations of developmental mechanisms
- explanations of highly conserved molecular genetic mechanisms,
like gene regulatory networks, and explanations of cellular-physical
mechanisms, like cell migration - sometimes a tradeoff emerges.
Rather than allowing a more complete explanation, integrating the two
mechanisms may lead to a less general explanation, since
non-phylogenetically conserved cellular-physical mechanisms yield less
generality in explanations. This tradeoff can introduce an explanatory
bias to projects that seek to integrate development and evolution. It
could lead researchers to favors the generality of explanations, which
cite highly conserved molecular genetic mechanisms and no
cellular-physical mechanisms, over integrated explanations citing both
kinds of mechanisms.



With respect to the concept of mechanism in developmental evolution,
Brigandt (2015) highlights that some mechanistic explanations in
evo-devo - like those on how development biases evolution
(Radersma et al. forthcoming), how novel variation arises through
developmental plasticity (Pigliucci 2001, Gilbert 2006), and how
organisms generate heritable, adaptive phenotypic variation
(evolvability; see Brown 2014) - significantly expand the
standard analysis of decomposition and localization by dynamical
models (see also Bechtel & Abrahamsen 2010; Brigandt 2013; Baedke
2020). These models allow predicting the dynamics of developing
systems. After decomposing a system and identifying causal
contributions of parts or sub-systems, dynamical models help to
demonstrate how these contributions operate together to bring about a
whole system's behavior. In this way, they answer how
developmental mechanisms create evolutionary relevant qualitative
changes in phenotypic properties, like robustness, phenotypic
plasticity, and modularity, through underlying quantitative changes in
their component parts and activities. One classical example of this
are mathematical models on the robustness of spatial pattering and
segmentation in *Drosophila*. They provide quantitative
information about the interaction of underlying gene network
components, including, for example, gene transcription rates and decay
rates of gene products (von Dassow et al. 2000).



Other discussions on the interface between development and evolution
focus on the structure of explanations that address how developmental
mechanisms evolve. Calcott (2009, 2013) has argues that Mayr's
distinction characterizes two kinds of explanation: developmental
explanation that answers 'How do *individuals* work
*at a time*?' and evolutionary explanation that answers
'How do *populations* change *over time*?'
However, there is a third kind, called 'lineage
explanation'. Lineage explanation differs from the above by
answering 'How do *individuals* change *over
time*?' Therefore, they offer a series of mechanistic
models, which trace differences between the developmental mechanisms
of individuals that produce the relevant morphological structures at
different times. Over evolutionary time, these relations undergo small
modifications, which ultimately bring about novelties, like eyes and
feathers, in the whole system. Thus, lineage explanation expands the
standards philosophical framework from a single description of a
mechanism into a series of mechanistic models.


### 5.2 The explanatory power of developmentalist explanations of evolution



Besides these debates about the structure of biological mechanisms and
their role in explaining developmental evolution, philosophers of
biology and biologists have discussed, more generally, which virtue
developmental explanations (could) have for addressing evolutionary
phenomena. Related to this issue is the question how much - in
the sense of what kind of facts - natural selection alone can
explain (see the entry
 adaptationism).
 It is widely accepted that such explanations can address the general
dynamics of trait frequencies and survival (see Sober 1984). However,
whether this also holds for addressing in more detail the development
of particular traits of individuals is an unsettled issue. While some
authors claim that evolutionary explanations by natural selection can
explain why a particular individual has a certain trait rather than
another trait (Neander 1995; Forber 2005) others deny this (Sober
1984; Stegmann 2010). What is more, it has been argued that
integrating explanations of developmental phenomena, like
developmental bias, phenotypic plasticity, niche construction, and inclusive inheritance, to the explanatory framework of evolutionary
theory would lead to a "significantly expanded explanatory
capacity" of this theory (Pigliucci & Muller 2010: 12).
However, while there is often agreement in evolutionary biology over
the existence of these developmental phenomena (Laland et al. 2014;
Wray et al. 2014), their explanatory relevance is questioned. Against
this background, scholars have begun analyzing based on which criteria
of explanatory power, like precision, proportionality, sensitivity,
and idealization, developmentalist evolutionary explanations are
better than selectionist explanations. This includes identifying,
which tradeoffs between explanatory standards (e.g., between precision
and sensitivity or idealization) those accounts face that seek to
integrate developmental and evolutionary explanations (Baedke et al.
2020b; Uller et al. 2020).


## 6. Anthropological and ethical dimensions of developmental evolution



The above debates about the relationship between evolution and
development primarily emerged within philosophy of science, especially
in history and philosophy of biology. However, there are other, more
general debates about anthropological and ethical issues that concern
developmental evolution. The primarily refer to how we conceptualize
developing and evolving humans, their life, body and health, as well
as how we assign responsibilities for health care interventions.



First, new findings in the plasticity of developing organism, their
interconnectedness, and modes of transgenerational transmission of
information have affected scientific and public understandings of what
humans are. For example, if humans are conceptualized as holobionts
- as collectives of co-developing and co-evolving organisms
- this also means that development is a matter of
co-construction, of interactions between species. It means, as Haraway
(2016) has phrased it, that we - as humans - very
literally 'become with others.' In this context,
sympoiesis (developmental symbiosis) means that development is
co-development. Against this background, John Dupre and Maureen
O'Malley (2009) see living entities as interactive collections:
"Life, we claim, is typically found at the collaborative
intersections of many lineages, and we even suggest that collaboration
should be seen as a central characteristic of living
matter".



Second, biological and biophilosophical debates on developmental
evolution and organisms' plasticity and environmental
responsiveness have informed debates on what the human body is. For
example, Jorg Niewohner (2011) states that a new concept of
the human body is currently emerging in modern biology, the so-called
'embedded body'. According to this view, the human body is
no longer a machine-like unit, which is genetically programmed,
neurally controlled and bounded by the skin, but an open and dynamic
unit which cannot be grasped in isolation from its material and social
environment (see also Baedke 2017). Additionally, the body is embedded
into different time scales ranging from its evolutionary and
transgenerational to ontogenetic past, which permanently constitute
its present. Others have argued, against the standard human birth
narrative and Aristotle, who defined the temporal boundaries of
individuals at birth and death, that birth in humans is not the
creation of a new individual. Instead, birth should be understood as
the origin of a new multi-species collective (Gilbert 2014; Chiu &
Gilbert 2015).



Another anthropological issue arising from recent research in evo-devo
and epigenetics is, third, the question how to define normality and
health in humans (see Baedke 2019b). There is evidence that bacteria
are needed for our normal cognitive and social development. For
example, germ-free mice are asocial and have autistic-like behavior
(Desbonnet et al. 2014) and this behavior can be replicated by
implanting the microbiome from autistic patients (but not control
patients) into germ-free mice (Sharon et al. 2019). Such cases suggest
that biological normality is not as intrinsic property to organisms
but emerges through interconnections with other organisms and the
environment. In addition, our understanding of health is increasingly
challenged. This especially refers to the view that describes human
health as freedom and autonomy from external interference. It usually
sees bacteria as deviations from the norm and parasitism as
pathological, because it threatens and contaminates the purity of the
individual's energy pattern. Instead, in a (more processual)
holobiontic framework, microbes are needed for normal development and
are thought to prevent the development of certain diseases (Bello et
al. 2018; Kirjavainen et al. 2019). In addition, certain entities,
bacteria or viruses, previously thought to be harmful, are now
increasingly considered to be 'good' or
'healthy' collaborators, not 'bad intruders'
(Dupre & Guttinger 2016). In more general term, this means
that since microbiota are increasingly recognized as important
components that stabilize normal development and co-evolve with
humans, they therefore carry traits crucial for humans' fitness,
i.e., health. This new perspective could lead to radical changes in
personalized surveillance and treatment of disease, and, more
generally, to new strategies in policy making, which replace the idea
of preserving the autonomous individual from contamination by the idea
of maintaining (equilibrium states of) collectives of co-developing
and co-evolving individuals.



Finally, on a more ethical dimension, these findings about
humans' openness to their environments and to one another has
led, first, to discussions about who takes responsibilities for
humans' health states and interventions (e.g., on epigenomes and
microbiomes) on intra- and transgenerational timescales (Dupras &
Ravitsky 2016). If plastic development can shape evolution, who is
responsible for developmental outcomes and evolutionary trajectories
in humans? Should the individual being as the central heath care
agent, which is 'freed from the chains of its genes'
(Pickersgill et al. 2013), take this responsibility? Or should
collectives, such as national states or international bodies, be
responsible for levels of toxins in the environment as well as for the
food individuals eat and stress they are exposed to (Hedlund 2012)?
The latter account of responsibility aims to prevent overemphasizing
the causal role of mothers as the most central public health care
agents who should be held accountable (and guilty) if their children
or later generations become sick (Richardson et al. 2014).


### 7. Concluding Remarks



The relationship between evolution and development has been a long
debated topic in the history of biology and philosophy of biology.
This entry has sampled a small portion of work relevant to the
conceptual, epistemological, anthropological and ethical reflections
on this relationship. Besides the issues discussed here, philosophers
of biology and biologists have discussed how developmental and
phylogenetic approaches to homology can be integrated (Amundson 2004;
Wagner 2014; DiFrisco 2019; see the entry
 developmental biology),
 what model organisms (Love 2009; Lloyd et al. 2012; Minelli & Baedke 2014; Zuk et al.
2014; see entry
 developmental biology)
 and representational tools scientists (should) use for studying
relationships between evolution and development (e.g., normal plates,
cell fate maps, epigenetic landscapes) and what the epistemic and
heuristic roles of these tools in scientific practice are (see Haraway
1976; Gilbert 1991; Hopwood 2007; Love 2010; Baedke 2013; Baedke &
Schottler 2017; Nicoglou 2018). In addition, long standing
debates on teleology in biology (see the entry
 teleological notions in biology)
 drew on the relation between evolution and development to distinguish
the teleological dimension of development from non-teleological
evolutionary processes (Mayr 1961), to introduce new conceptual
frameworks, like teleonomy, which refer to only apparently purposeful
systems (Pittendrigh 1958), or to highlight the purposeful acting
organismic agent as a starting point to reason about the teleological
nature of evolution (Russell 1950; Piaget 1976 [1978]; Walsh
2015).



At the moment, philosophical debates about the appropriate conceptual
and explanatory approach to combine or integrate developmental and
evolutionary processes have not reached a consensus. This is not least
due to the fact that the relevant disciplinary fields, such as
evo-devo, epigenetics and niche construction theory, which foster such
integration, are still relatively young. Their theoretical and
conceptual frameworks are highly heterogeneous. Thus, important aims
for future philosophical research is to understand obstacles for the
stabilization and solidification of these frameworks, to identify
their explanatory virtues and limitations, as well as to call
attention to their effects on how we understand humans and human
health.