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Living systems are complex systems made of components that
tend to degrade, but nonetheless they maintain themselves far
from equilibrium. This requires living systems to extract energy
and materials from the environment and use them to build and
repair their parts by regulating their activities based on their
internal and external conditions in ways that allow them to keep The Philosophy
living. The philosophical and theoretical approach discussed of Biology
in this Element aims to explain these features of biological
systems by appealing to their organization. It addresses classical
and more recent issues in philosophy of biology, from origins
and definitions of life to biological teleology and functions,
Biological
from an original perspective mainly focused on the living
system, its physiology and behavior, rather than evolution.
It discusses and revises the conceptual foundations of this
Organization
approach and presents an updated version of it. This title is also
available as Open Access on Cambridge Core.
About the Series Series Editors

This Cambridge Elements series provides Grant Ramsey
concise and structured introductions to KU Leuven
Leonardo Bich
all of the central topics in the philosophy Michael Ruse
of biology. Contributors to the series Florida State
are cutting-edge researchers who offer University
balanced, comprehensive coverage
of multiple perspectives, while also
developing new ideas and arguments
from a unique viewpoint.
This title is also available as Open Access on

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Elements in the Philosophy of Biology
edited by
Grant Ramsey
KU Leuven
Michael Ruse
Florida State University
BIOLOGICAL
ORGANIZATION
Leonardo Bich
University of the Basque Country (UPV/EHU)
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DOI: 10.1017/9781009393959
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Elements in the Philosophy of Biology
DOI: 10.1017/9781009393959
First published online: December 2024
Leonardo Bich
University of the Basque Country (UPV/EHU)
Author for correspondence: Leonardo Bich, [email protected]
Abstract: Living systems are complex systems made of components

that tend to degrade, but nonetheless they maintain themselves far
from equilibrium. This requires living systems to extract energy and
materials from the environment and use them to build and repair their
parts by regulating their activities based on their internal and external
conditions in ways that allow them to keep living. The philosophical and
theoretical approach discussed in this Element aims to explain these
features of biological systems by appealing to their organization. It
addresses classical and more recent issues in philosophy of biology,
from origins and definitions of life to biological teleology and functions,
from an original perspective mainly focused on the living system, its
physiology and behavior, rather than evolution. It discusses and revises
the conceptual foundations of this approach and presents an updated
version of it. This title is also available as Open Access on
Cambridge Core.
Keywords: organization, autonomy, control, mechanism, organisms
© Leonardo Bich 2024

ISBNs: 9781009539401 (HB), 9781009393966 (PB), 9781009393959 (OC)
ISSNs: 2515-1126 (online), 2515-1118 (print)
Contents
1 Introduction: Understanding What Makes a System Living 1
2 Different Uses of Organization: Organizational Motifs,

Organizing Principles, and the Organizational Framework 5
3 Biological Organization as a Self-Maintaining Causal

Regime: From Autopoiesis to Closure of Constraints 13
4 Reinterpreting Closure: From Basic Self-Maintenance

to Regulatory Control 22
5 Naturalizing Biological Teleology and Functions 32
6 Interpreting Biological Phenomena through the Lens

of Organization 41
7 Bridging Philosophical Frameworks: Organization

and Mechanisms 48
8 Open Challenges: Symbiotic Associations and the

Environment 55
References 63
Biological Organization 1
1 Introduction: Understanding What Makes a System Living

Organisms are complex systems made of soft materials that tend to degrade, but
they maintain themselves through the constant turnover of their components. At
first glance, they might seem very fragile compared to other natural systems or
to human-made artifacts. Artifacts, for example, can have very resistant parts,
which can remain unchanged for a long time. Organisms, instead, are subject to
the constant degradation and transformation of their components, which need to
be continuously replaced or repaired. They are made of components, such as
proteins, which are highly dynamic, have a short lifespan and are constantly
transformed. Proteins spontaneously degrade, or they can lose their functional
shape (denaturation) due to changes in the properties of their surroundings such
as temperature, pH, and interactions with other molecules. Moreover, they can
be degraded by the organisms when they cannot perform their activity anymore
or such activity is not needed, and their parts can be recycled to build new
proteins. Another important difference is that while entities like rocks or even
most artifacts can just persist for a very long time without performing any
activity, living organisms cannot shut down their own processes – apart from
extreme cases such as bacterial spores, and even in those case only partially –
but on the contrary, they need to procure nutrients from which to extract the
energy and matter necessary to run their metabolism, to ensure the turnover of
their parts, or to move in and interact with their environment.
Despite the fragility of their components and the need to continuously act (or,
better, by virtue of these properties), individual organisms and life on Earth
more generally, exhibit remarkable resilience. While artifacts, once damaged,
stay so and cannot function, living organisms, instead, can repair or replace their
parts. They can shut down some of their more demanding activities and mobil-
ize their resources to respond to stress, and they can recover from severe
damages. Importantly, while artifacts are made to work under a fixed set of
conditions – although in recent trends the aim is to design more flexible
artifacts – organisms can function in different ways under different conditions.
It is thanks to these capabilities that plants can survive herbicides and can grow
in areas contaminated by toxic waste, or that bacteria can resist antibiotics and
can live in almost all environments from the stratosphere to the depths of the
Earth crust, under a variety of conditions that include extreme temperatures, pH,
pressure, and so on. Together with plants, fungi, and unicellular organisms,
animal life was even able to survive the consequences of the impacts of
asteroids.
Organisms, taken individually or in groups, exhibit a great flexibility that
allows them to cope with continuously changing conditions in their environment
2 Philosophy of Biology
but also within themselves. For example, they can modify their internal physi-
ology or their behavior depending on changes in the environmental temperature
(Hagen, 2021) or in the type and amounts of food available (e.g. synthesizing
different enzymes to digest different sources of nutrients), on the specific phase of
their life cycle (e.g. growth, migration, reproduction, etc.), on the presence of prey
or predators, on the state of other organisms, and on the presence of light or
darkness.
Let us illustrate this by briefly mentioning three examples of radical changes
adopted by relatively simple organisms. The first is the case of Choanoflagellates
of the species Salpingoeca rosetta: eukaryotic organisms that can live as free
unicellular systems. In response to diverse environmental cues, they can change
their way of living, and adopt multicellular modes of association by forming
simple chains or spherical colonies kept together by cytoplasmatic bridges and
extracellular matrix (Larson et al., 2020). The second example is related to the
presence or absence of light. The cycle of light and darkness can determine when
to look for prey or whether it is safe to move about in the environment. It can also
influence metabolic activities. An interesting case of the capability of adapting to
the presence and absence of light is circadian rhythms, which can be identified
in many living organisms, from bacteria to plants and animals. Let us focus
on bacteria. They are very small organisms. The internal space and the energy
available to them are very limited. In photosynthetic bacteria such as cyanobac-
teria, keeping photosynthesis mechanisms at work during the day is an important
source of energy, but during darkness is a waste of resources. Moreover, the
oxygen produced by photosynthesis is toxic to the enzyme nitrogenase, involved
in nitrogen fixation, another important activity necessary for their maintenance.
Therefore, these two different processes, photosynthesis and nitrogen fixation,
need to be kept separate. These two activities are usually performed by different
organisms. However, the cyanobacterium Synechococcus can do both activities
by segregating photosynthesis and nitrogen fixation in time: day and night,
respectively. Its circadian clock can keep track of light–dark cycles in its envir-
onment and activate the expression of different genes accordingly, thus modulat-
ing its physiological activities (Cohen & Golden, 2015; Bechtel & Bich, 2021).
The third example concerns changes on the basis of the state of other organisms.
From bacteria to fungi, plants, and animals, living systems employ a variety of
strategies and mechanisms that allow them to communicate with one another and
coordinate their activities, including metabolism, foraging, and reproductive
behavior. A basic case is quorum sensing in bacteria. It involves individual
bacteria synthesizing and releasing into the environment a molecule, an auto-
inducer, while sensing and responding to the concentration of that same molecule
in their surroundings. The bond between these signaling molecules and their
bacterial receptors activates the expression of several genes, including those

involved in the synthesis of these same signal molecules. In this way, when
more bacteria respond to the concentration registered by their own receptors by
producing more autoinducers, the signal is amplified. Quorum sensing provides
a way for individual bacteria to regulate their activities depending on the number
and state of other bacteria available nearby, whether of the same species or of
other species, thus allowing them to coordinate activities such as aggregation, the
formation, growth and disassembly of biofilms, and collective movement.
These are just a few examples of the fact that, even in their most basic forms,
living organisms, despite their apparent fragility (and the fragility of their parts),
can exhibit remarkable resilience and versatility. One of the reasons is that –
unlike human artifacts, which are produced from without – living systems have
the capability to produce, repair, transform, and replace their parts. The other
reason is that organisms do not just replace and repair their parts. They also
modify themselves and what they do on the basis of their internal physiological
state and environmental conditions. They are not just alive but employ a variety
of activities that allow them to keep living. These two properties, self-production
and self-regulation, go hand in hand: Organisms maintain themselves alive and
they can do so because they are constantly changing.
These capabilities, as we observe them now, can be understood as the result of
a long history of evolution by natural selection, which took place over a span of
more than three billion years since the origin of life – not including prebiotic
evolution, where the main features that characterize unicellular organisms have
been established – and produced continuous lineages of organisms. However, it
is important to consider that, in turn, it is the very ability of each given organism
to maintain itself and keep living under different and often threatening condi-
tions that has allowed its survival and reproduction in its environment, and
therefore made evolution possible. While not denying the importance and role
of evolutionary considerations, a possible research avenue to understand these
distinctive features of living organisms is to investigate how organisms, rather
than their lineages, are maintained, by focusing on their physiologies and
behaviors.
The philosophical and theoretical framework discussed in this Element aims
to do so by explaining these features of biological systems in terms of their
organization. This framework characterizes a biological organism as a system
capable of producing its own components, regulating its activities, and main-
taining itself while interacting with its environment. To explain this capacity,
this tradition appeals to the internal organization of the organism, which is
maintained despite the continuous transformations that the organism undergoes
at the level of its components. According to the advocates of this approach, it is
the organization of a system – that is, the set of relations between its compo-
nents, rather than the properties of specific components – that defines it as
a system of a particular class and that needs to be maintained for the system to
keep its identity as a member of that class (Maturana & Varela, 1980: xx). In the
case of living systems, the organization to be maintained is the one connecting
production and transformation processes, and the activities of the components
of a living system. This specific organization makes the system able to synthe-
size the very components that make it up, and run its internal processes, by using
energy and matter from the environment. This organization is often called “autono-
mous” (Varela, 1979; Moreno & Mossio, 2015), because by realizing it living
systems are considered as the source of their own activities and through such
activities they contribute, at least in part, to their own existence (see Sections 3–5).
Inspired by the work of Claude Bernard, and by Cybernetics, Systems Theory,
and Theoretical Biology, the organizational framework was built upon pioneering
work on biological organization (also known under the label of “biological auton-
omy tradition”) carried out by Jean Piaget (1967), Robert Rosen (1972), Humberto
Maturana and Francisco Varela (Varela et al., 1974), and Howard Pattee (1972).
More recently it has been further developed, among others, by Stuart Kauffman
(2000) and by Alvaro Moreno and collaborators (e.g. Moreno & Mossio, 2015).
Work based on the organizational perspective is gaining traction and has been
raising increased interest in the past few years. This framework is being applied in
the philosophy of biology to a wide range of topics, spanning from origins and
definitions of life to biological teleology and functions, and to biological explan-
ations. One of its distinctive features is that it addresses classical and more recent
issues in the philosophy of biology from an original perspective mainly focused on
the organism, its physiology and behavior, rather than evolution.
The Element presents and discusses the core ideas of this framework and how
they originated. It revises its conceptual foundations and provides an updated
view that analyzes in detail how these ideas are being developed by recent and
current research – from the introduction of the notion of closure of constraint to
that of regulatory control – and are being applied in the philosophy of biology.
Section 2 clarifies the differences between this and other uses of the notion of
organization in the philosophy of biology, such as network motifs and organizing
or design principles. Section 3 analyzes the main attempts to develop a framework
able to capture the distinctive features of biological organization, from the notion
of autopoiesis to that of closure of constraints. Section 4 discusses recent work
focused on regulatory control aimed at revising the conceptual core of the
framework and overcoming some of the simplifications or limitations of previous
accounts. It further develops this framework from an idea of organization based
on the production, repair, and replacement of the parts, to one that includes the
integration and modulation of their activities and explains the versatility of living
organisms. Section 5 discusses applications of the organizational framework to
philosophical issues such as biological teleology and functions. Section 6
addresses applications of this framework to specific biological phenomena such
as origins of life and biological communication, which exemplify some of the
core operational and explanatory features of this framework. Section 7 puts this
framework into a wider context by discussing the relationships between this
research tradition and new mechanism in producing biological explanations.
Section 8 introduces the reader to some open challenges to this approach, coming
from the debates on biological individuality and symbiosis and on the role of the
environment, and sketches possible ways to address them.
2 Different Uses of Organization: Organizational Motifs,

Organizing Principles, and the Organizational Framework
This section distinguishes between different, yet closely related, ways of talking
about biological organization. It addresses three examples: organizational motifs,
organizing or design principles, and the organizational framework. Before dis-
cussing their features and differences, let us focus first on what they have in
common: a general idea of organization, common origins, and some common
epistemic roles.
The term “organization” generally refers to the structure of relations between the
parts of a given system or of a subsystem of a larger system, be they components,
their activities, or processes. Together with reference to the types of components,
organization is often used to characterize a system as an entity of a given class:
For example, depending on how they are spatially organized, wooden parts
can constitute a chair or a table, and mechanical parts a motorcycle or a car.
Organization can mean different things in different contexts (physical, chemical,
biological, in artifacts, etc.) and it can refer to different types of relations: for
example, spatial ones, like in the map of a subway system, or temporal, such as in a
succession of events. Each domain of investigation makes different distinctions
when identifying a system: Different kinds of relations are considered as pertinent
in order to describe the phenomena object of study, and different operations of
partition are performed in order to extract the relevant components. Let us think,
for example, of how many system domains can be found in a human body: from
molecular and cellular ones to complexes of organs (e.g. the digestive or the
vascular system), up to ecosystems such as the gut, populated by our bacterial
symbionts. As a consequence, the same material entity can in principle be
described in terms of different kinds of systems, each with specific components
and organization.
The way organization has been addressed in biology by the theoretical

tradition discussed in this Element is in causal terms: as a pattern of causal
connectivity. A causal account of organization, as discussed by Levy and
Bechtel (2013: 243), “involves an internal division of labor whereby different
components perform different causal roles.” Systems that do not involve differ-
ential causal roles for their components are not organized. Causal connectivity
can be characterized in different ways: for example, in terms of how parts and
processes produce a particular output of a system, in terms of the degree of
connectivity between the parts of a system, and so on.
Current uses of the notion of organization in biology are mainly grounded
in two closely interconnected research traditions of the twentieth century:
Cybernetics and System Theory. Both traditions can be characterized as
attempts to cut across disciplinary fields to take inspirations from different
phenomena and favor the exchange of concepts and models. These tradi-
tions, often overlapping, have the ultimate goal of studying concepts and
building research tools that can be fruitfully applied to study and intervene
in a wide range of phenomena from heterogeneous fields, but that exhibit
some common abstract features. For these reasons, Cybernetics and Systems
Theory have been characterized by the participation of researchers from
a wide range of disciplines.
The term “cybernetics” was coined in the late forties of the twentieth century
(Wiener, 1948), as the science of “steersmanship” or control (from the ancient
Greek word “kybernetes,” which means steersman). It was established as
a research tradition in the context of the Macy Conferences, a series of interdis-
ciplinary conferences that were held at the Josiah Macy Jr. Foundation in
New York from 1946 to 1953 (McCulloch, 1974; Pias, 2016). Since then, it has
been focused on two main activities: (1) the study of patterns of organization
common to different phenomena, usually subsystems of a larger system; (2) the
development of formal descriptions of these patterns of connectivity that could be
applied in different disciplines, from engineering to biology, psychology, neuro-
physiology, and social sciences (Wiener, 1948; Ashby, 1956; Pickering, 2010).
This approach has been employed in different directions, such as for example
the application of mathematical logic to study the functioning of the nervous
system and to show how the nervous system could implement formal logic, and
the development of information theory and computing machines. One of the main
foci has been on the study and formalization of feedback mechanisms to under-
stand control and stabilization in biological systems and human-made machines.
Negative feedback describes phenomena in which the value of the output of
a system is used to modify the activity of the system (the output “feeds back”) in
such a way as to create a loop that reduces fluctuations in the output itself, and to
maintain its value stable within a specific range.1 Feedback mechanisms are
characterized by a distinctive pattern of connections: a circular causal relation
between a controller and a controlled subsystem. The controller is a sensory-
effector subsystem that senses both the external inputs to the system and the
outputs of the controlled subsystem, and acts as an effector on the controlled
subsystem by modifying its activity. The loop is established because the outputs
of the controller are the inputs of the controlled subsystem, and in turn, the outputs
of the controlled subsystem are part of the inputs of the controller. Feedback
mechanisms are control devices that, although not specific to biology, have
become since the thirties an important tool in different areas of biology (e.g.
neurophysiology, see for instance McCulloch, 1974), often in association with the
idea of homeostasis (Cannon, 1929). Since then, they have been used to model
and understand dynamically stable situations in which the value of a variable
appears to be actively maintained within a given range. The main strategy
employed to study them has been to analyze the technological mechanisms
of stabilization in artifacts to advance hypotheses on the functioning of
biological ones and vice versa to exploit the knowledge of the latter for the
implementation of the former.
Although they share the core idea, different models vary in terms of the number
and kind of elements constituting negative feedback mechanisms. One may be
familiar with a thermostat, a device that measures the temperature of a space such
as a room and, depending on the deviation of the measured temperature from
a value set by the user, it activates or deactivates an effector device, such as
a heater, so as to keep the room temperature stable. Let us consider a basic but
illustrative example of biological negative feedback, the case of allosteric feed-
back inhibition (Figure 1), discovered and conceptualized by Monod et al. (1963)
in molecular biology. Allosteric control is the change in the shape and functioning
of a protein (inhibition or activation) due to the interaction with an effector
molecule in a site different from the active one where catalysis takes place.
Given a metabolic pathway with supply of reactants from the outside (the
input) in which reactions at each step (A→B, B→C, . . . →N) are catalyzed by
a different type of enzymes (E, E’, E’’ . . . En), a feedback loop of allosteric
inhibition is realized when the enzymes E, which for example catalyze the
reaction A→B, are allosterically inhibited by one of the products of this pathway:
a metabolite N. As a result, when the concentration of N is above a given
threshold, the activities of Es are inhibited and so is the pathway responsible for
the production of N, thus avoiding the accumulation of this metabolite in the
1
Under specific conditions, feedback loops can themselves create fluctuations or oscillations:
a capacity often employed to create and sustain rhythmic phenomena.
Figure 1 A basic example of negative feedback loop from molecular biology:

allosteric feedback inhibition in a metabolic pathway. The catalytic activity of
an enzyme E in the pathway is inhibited by the interaction with a metabolite N,
which is produced in the pathway (from Bich et al., 2016, reproduced with
permission from Springer Nature).
system. A pathway so organized with a negative feedback mechanism realizes

a loop where the components E, the controllers, can change their conformation
and exhibit at least two possible states, active or inhibited, when free or bound
to N respectively. The components E act as both sensors of the value of the
controlled variable N (at the allosteric site) and effectors (at the catalytic site)
acting on the process of production of N.
The core approach of Cybernetics is to establish isomorphisms between
patterns of connectivity, such as feedback loops, common to different systems,
and to develop general abstract tools to study, model, or design them. The
main idea underlying the cybernetic tradition is that what is responsible for
a given behavior or phenomenon is the way of connecting components, and
this can be shared by different types of systems regardless of their material
realization. It is such an organization, more than the underlying physical
structure, which would provide the means to understand, model, and design
a phenomenon. This is exactly what allows cyberneticians to transfer models
from one domain to another: abstracting from the intrinsic properties of the
material components of a specific physical instantiation of a mechanism such
as a feedback loop (from a thermostat to allosteric inhibition, to physiological
phenomena such as the regulation of glycemia or the control of body tempera-
ture, of blood oxygen, etc.) to focus on the modes of causal connections between
the parts.
General Systems Theory refers, broadly speaking, to a more general frame-
work mainly aiming at the development of an integrated, unified science of
wholeness and organization, into which cybernetics can also be integrated (see
also Pouvreau & Drack, 2007). Its roots can be traced back to the thirties of the
twentieth century with the studies conducted by Ludwig von Bertalanffy on
developmental processes and on living organisms as thermodynamically open
systems, which ascribe an important role to organization and more precisely to
the nonlinear interactions between components. Developed in close parallel

with Cybernetics, its theoretical foundations were laid in the late sixties (von
Bertalanffy, 1968; Klir, 1991).
One of the central tenets of General System Theory is that in order to
understand a system one has to consider it in its totality, rather than as a sum of
preexisting components. According to von Bertalanffy, the reason for this is that
the relations between the components modify their behaviors, giving rise to
global emergent properties and phenomena that cannot be found by studying
the individual components. The main research lines in this tradition include: the
search for “laws of organization” governing emergent phenomena in which the
behavior of parts depends on the whole; the study of general properties of
systems; discussion of the differences between organisms and machines;2 and
the study of the dynamic nature of organisms as essentially active systems, which
respond to external stimuli through structural changes. The goal is to find
homologies between different types of phenomena that share, like to those studied
by cybernetics, some common abstract features independent of the specific prop-
erties of the material parts, and to develop a common perspective for different
sciences.
General System Theory pursues the unification of sciences by developing
general approaches that do not imply reduction to a more fundamental science.
Its approach consists instead of developing a common perspective, with
a shared vocabulary and invariant concepts, tools, and laws applicable across
different fields that favor exchanges of ideas, questions, and solutions between
disciplines. Examples of these special systems laws, which in principle depend
on organization, include the exponential law for growth,3 Shannon theorem
about the maximum amount of information that can be transmitted through
a channel, or Ashby’s principle of requisite variety for control systems, accord-
ing to which in order to block all possible perturbations a controller needs to
have at least as many possible states as the environment or the other subsystems
with which it is going to interact.
In sum, Cybernetics is focused on pinpointing specific patterns of organiza-
tion such as feedback loops, establishing isomorphisms between specific
instances of them by means of abstract mathematical tools, and then applying
them to specific cases by adding more details. General Systems Theory,
2
This is an important difference with Cybernetics, which was focused instead on identifying and
investigating similarities between organisms and machines with the aim to establish exchanges of
concepts and models between these two different domains and develop new research lines and
applications.
3
An example is the growth of a population of bacteria in the presence of food. Bacteria reproduce
by division and the number of bacteria doubles at each generation. The number of new bacteria is
therefore proportional to the present population, and it increases at each new generation.
instead, aims to unify: to develop higher-order laws and general principles that
can bring together descriptions and inform theoretical thinking (Green &
Wolkenhauer, 2013).
The different uses of the notion of organization at work today in biology and
philosophy of biology, such as organizational motifs, organizational or design
principles, and the organizational framework, all share these common origins in
Cybernetics and Systems Theory and the core idea of organization as a pattern
of causal connections. However, each puts more emphasis on different aspects
of this heritage. The distinction between them is not always clear-cut, as their
uses often tend to overlap. Nonetheless they differ in scale, purpose, and
epistemic role. Their discussion here is not exhaustive but aims to clarify their
uses and put the organizational framework into perspective.
One way to talk of organization in biology is in terms of motifs of connectiv-
ity. This refers to the way processes and components are wired in small
networks, such as different types of negative feedback loops. The aim is to
understand the type of behavior a circuit thus obtained may exhibit. This
approach closely follows the Cybernetic tradition and focuses on studying
local patterns of connectivity, modeling them, and establishing isomorphisms
between their instances in different systems. An example of this approach is Uri
Alon’s work on biological circuits in systems biology. This work is aimed at
identifying and modeling mathematically local wiring patterns (“network
motifs”) in different biological phenomena (Alon, 2007). It is mainly focused
on gene transcription networks, in which transcription factors encoded by
a gene affect the transcription rate of another gene. Alon describes them in
organizational terms as graphs in which nodes are the parts (the genes), and the
edges are causal interactions (the modulation of transcription rates of other
genes). Studying these transcription networks, Alon identifies what he calls
“network motifs,” that is, a small set of patterns that occur in actual networks
significantly more often than in randomized networks. He then hypothesizes
that the reason why these motifs are recurrent in a genome and are common
to different organisms4 is that they must enable the component elements to
perform specific activities that are important for the system. Therefore, they
need to be further studied and modeled.
These small circuits constitute the building blocks from which larger networks
are built. Scientists can identify them based on their recurrence, and describe and
compare their properties and function through mathematical modeling. Then they
can see if the same motifs appear in other biological networks and apply the same
4
They have been studied for example in model organisms such as the bacterium Escherichia coli or
the eukaryotic yeast Saccharomyces cerevisiae.
modeling tools to understand their behaviors. Examples of this are protein

modifications in signal transduction networks, or networks of synaptic connec-
tion in the worm Caenorhabditis elegans (Alon, 2007).
Organizing or design principles, as discussed by Green and Wolkenhauer
(2013), instead refer to robust generalizations that aim to capture “dynamic and
functional relations in a class of systems” without the details of a concrete
mechanism in a specific context. They are wider and more general notions than
motifs, and they usually refer to properties exhibited by larger organized systems
rather than specific circuits. A paradigmatic example is Cannon’s notion of
homeostasis, that is, the capability of a physiological system to resist perturbations
by maintaining some of its variables (e.g. pH, temperature, etc.) stable within
a narrow range or, more generally, its internal conditions in a steady state.5
Another principle is optimality, which is the capability of a biological system to
maximize or minimize some function under given constraints. An example is the
vascular system, considered as organized in each species in such a way as to
maximize blood flow.
Organizing principles, in line with the tradition of General System Theory,
provide explanations of how certain classes of organized systems work in
principle and exhibit some general properties. However, they do not necessarily
take the form of unifying general laws such as those pursued by General System
Theory, but of pragmatic generalizations. They constitute sketches of explan-
ations that abstract from details while focusing on some essential dynamics,
used to build more detailed explanations in specific cases. Generalization across
systems is then achieved by identifying what fundamental principles, such as
optimality or homeostasis, some systems have in common, by investigating
why they do so (e.g. whether they share some underlying mechanisms or a
common dynamic behavior), and by developing modeling tools (Green &
Jones, 2016).
Organizational motifs and organizing principles differ in the degree of
generality and their focus on organizational building blocks and general prop-
erties, respectively. However, due to their shared focus on organization rather
than material details, they exhibit common elements such as abstraction and
decontextualization of certain mechanisms and properties. This allows scien-
tists to develop epistemic tools for cross-disciplinary exchanges and applica-
tions and for the discovery of similar phenomena in other systems.
Lastly, let us look at a third use of the notion of organization in biology: the
organizational framework. It differs from the other two approaches discussed in
5
Organizing principles may include motifs, such as feedback, as special cases. Homeostasis, for
example, can be realized through (multiple) negative feedback loops, but also by other means
such as buffers, so that it does not coincide with one specific motif.
this section, in that the object of interest is not part of a network or a given
property of a system, but the whole living organism. This approach brings
together the quest for the generality of systems theory and the focus on patterns
of connections of cybernetics under a different aim: to characterize the distinct-
ive pattern of connectivity of a whole biological organization.6 The primary
focus here is on developing a theory that integrates into a coherent picture
different principles, phenomena, mechanisms, and properties in the context of
the organism. Abstraction is still very important but is pursued in a different
sense, by identifying what is common to all living systems despite their material
differences.
The origin of this attitude can be traced back, for example, to the theoretical
work on Relational Biology carried out by Nicholas Rashevsky (1954) at the
crossroads of Cybernetic and Systems Theory. His purpose was to develop
a mathematical theory able to treat the integrated activity of the organism as
a whole. According to Rashevsky, this can be achieved by looking for the
minimal network of connections between biological properties that is com-
mon to all living organisms. Like cyberneticians, he is interested in establish-
ing isomorphisms between different instances of a given type of organization.
However, he does not look at local patterns such as feedback loops, but he
focuses instead on finding isomorphisms between whole organisms, and
identifying which basic relations are preserved. This approach is built on
three assumptions: (1) the crucial importance of relations over material
details, (2) the need to focus on the minimal set of relations between parts
realized in all organisms, and (3) the possibility to study living systems
starting from their common organization. He does not provide a hypothesis
regarding the shape taken by this organization, but he suggests proceeding
bottom-up by identifying sets of basic functions in different organisms and
connecting them to describe how they are related. The common relations
resulting from mapping one relational diagram to another would be the
hypothetical relational structure of the minimal organization common to all
living systems.
This is a distinctive way to think about biological organization. It aims to
abstract from the multitude of structural components and processes to identify
the minimal pattern of connectivity that makes a system a living organism, and
it aims to use it to provide a theoretical understanding of biological systems. The
next sections discuss how the organizational framework develops this approach
in a distinctive way.
6
As will be explained in detail in the next section, unlike cybernetics the organizational framework
puts a special emphasis on the generative relations involved in the production of the system and its
parts.
3 Biological Organization as a Self-Maintaining Causal Regime:

From Autopoiesis to Closure of Constraints
The idea at the foundation of the organizational framework is that living
systems are capable of constructing, repairing, transforming, and maintaining
their parts, and consequently themselves, and they do so by using matter and
energy extracted from their environment. The organizational framework was
built upon the contributions of numerous theorists in the late sixties and early
seventies including Jean Piaget (1967), Robert Rosen (1972), Humberto
Maturana and Francisco Varela (Varela et al., 1974), and Tibor Ganti (1975),
who have emphasized the importance of self-maintenance, characterized in
terms of production and renovation of components.7 To explain the capacity
of biological systems to persist despite the turnover of very fragile and dynamic
components such as proteins, this tradition appeals to the internal organization
of the organism. This is what is maintained despite the continuous transform-
ations that the organism undergoes at the level of its part. Due to the emphasis
on the capacity of living systems to build and maintain themselves from within,
this research line has also been known as the tradition of “biological autonomy”
(Varela, 1979): to quote Kauffman (2000), in virtue of these properties living
systems are autonomous because they are capable of “acting on their own
behalf” without being completely driven by external factors.
These ideas were developed with the aim to build a new perspective in
theoretical biology focused on providing an understanding of what living
systems and their distinctive features are. One aim was to identify the differ-
ences between living systems and physico-chemical dynamical systems cap-
able of persisting in time and of generating ordered structures, such as
dissipative structures described in physics by Prigogine and collaborators
(Glansdorff & Prigogine, 1971). The other aim was to provide an alternative
approach to mainstream evolutionary and molecular biology, which were
focused on two levels of description: the level of populations, lineages and
species, and the molecular level. According to organizational theorists both
these approaches were missing what they considered the fundamental bio-
logical level, that is, the one of living systems considered as the most basic
biological units (Bich & Damiano, 2007). In this view, while theoretical work
at the evolutionary level was presupposing systems capable of maintaining
their viability in their environments and reproducing (Maturana & Varela,
1987), the work in molecular biology tended to identify properties and behav-
iors of biological systems with those of their molecular components, mainly
the genome (Maturana, 1978: 30). Consistent with their roots in the traditions
7
For historical analyses of this tradition, see Bich and Damiano (2008) and Letelier et al. (2011).
of cybernetics and systems theory, these theorists focused instead on what they
considered the central biological level: the organization of living systems.
These ideas were precursors of and in most cases have even directly inspired
the renewed interest in systems and organisms that has characterized theoret-
ical biology since the beginning of the twenty-first century (Gilbert & Sarkar,
2000; Woese, 2004; Cornish-Bowden, 2006; Etxeberria & Umerez, 2006;
Bich & Damiano, 2008; Nicholson, 2014). However, as pointed out by
Mossio, despite this new systemic trend, “organization still remains a blind
spot of biological thinking” (Mossio, 2023: 1).
The main objective of the early contributors to the organizational framework
was to develop concepts that identify and characterize aspects common to all
actual and possible manifestations of life, thereby revealing the features of
living systems that distinguish them from other classes of natural and artificial
systems. According to this framework, these features cannot be found in the
basic components of living systems (their material constitution or “structure”)
but in the ways these are related. The main reasons are two: (1) the same
components can participate in other kinds of systems, and (2) biological sys-
tems are characterized by the fact that components are constantly produced,
transformed, and degraded while the system as a whole persists. According to
early organizational theorists, focusing on the properties of individual compo-
nents risked leaving aside what makes the organism an integrated unity. This
thesis was advanced in sharp opposition to mainstream molecular biology,
represented by the theoretical and experimental work carried out by Francois
Jacob and Jacques Monod (Jacob, 1970; Monod, 1970), who focused on the
intrinsic properties of the material components of living systems: especially one
component, the DNA, which was singled out as the main if not the only
component responsible for the activity and reproduction of the organism.
The core feature of this approach is the focus on organization, that is, on the
identification of the relations between the operations of components and between
the processes of transformation carried out within a system. In this view, organ-
ization refers specifically to the way production and transformation processes are
connected so that they are able to synthesize the very components that make them
up. The fundamental feature of the organization of biological self-maintaining
systems is its circular topology as a network of processes of production of
components that in turn realize and maintain the network itself. This feature is
captured by the term autopoiesis, from the Greek “autos” (self) and “poiesis”
(production/creation): a regime of self-production or self-creation in which the
output of the activity of the system is the system itself (Varela et al., 1974). As
explained by Maturana (1980: 48): “The living organization is a circular organ-
ization which secures the production and maintenance of the components that
specify it in such a manner that the product of their functioning is the very same
organization that produces them.” It is an organization of highly dynamic com-
ponents whose effect is the production and maintenance of itself.
To characterize an organization that maintains itself while necessarily inter-
acting with its environment, this research tradition employs two main notions,
as introduced by Piaget (1967) and further elaborated by others. The first is
thermodynamic openness: To exist far from equilibrium, that is, to contrast
degradation or the thermodynamic tendency towards a homogeneous distribu-
tion (maximum disorder and minimum organization), a living system needs
matter from the environment in the form of building blocks from which to
produce its components, and energy to perform the activities required to maintain
itself and interact with a changing environment. The second notion, which is
specifically biological and aims to capture the distinctive feature of living sys-
tems, is organizational closure: A biological organization is characterized as
a closed (i.e. circular) network of processes of production in which each compo-
nent is produced by others in the network, such that the network maintains itself
despite the continuous change at the level of its parts and the continuous inter-
action with the environment. The interplay between openness in the material
dimension and closure in the organizational one ensures that matter and energy
are admitted to the system from outside, but the processes that generate the work
that continually remakes the organism are carried out by components produced by
these very processes. According to this perspective, living systems need to be
constantly at work to build and replace their components and extract from the
environment the matter and energy necessary to run their internal processes. To
use an expression by Bechtel, they are “endogenously active” (Bechtel, 2008) due
to the thermodynamic nature of biological organization, which combines at its
core endogenous activity with essential interaction with changing environments.
On this basis, this research tradition embraces a generative framework in
which there is a mutual dependence between the components of an organism,
such that the very existence of each component depends on its relationship
with the others and with the system as a whole. Despite the common focus on
relations, the organizational approach follows a different pathway from
Rashevsky’s Relational Biology discussed in the previous section. Instead
of proceeding from the bottom up by identifying individual properties and
functions and attempting to connect them, the organizational approach pro-
ceeds top-down. It recognizes the strong integration between mutually
dependent components and processes in living organisms, which are capable
of producing their parts and maintaining themselves, and it tries to understand
which minimal organization is necessary to realize it. Once this organization
is characterized, details can be filled in and it can be used to shed light on

different biological phenomena in the context of the organism.8
The early organizational tradition is subject to two main limits. One is that
these accounts are extremely abstract. One reason for this can be found in the
heritage of Cybernetics and its emphasis on formal characterizations of organ-
isms. Such formal analysis allows for multiple realizability: Different types
of biological, physical, and mechanical components could realize the same
abstract relations, such as feedback loops (see e.g. Varela & Maturana, 1972).
A further reason is that advocates of the organizational or autonomy tradition
sought to distinguish living organisms from other non-biological examples of
far-from-equilibrium systems that were being advanced at the time in the
physical sciences, such as dissipative structures (Glansdorff & Prigogine, 1971)
like convection flows, hurricanes, whirlpools, and so on: thermodynamically
open systems that realize stable patterns by consuming energy from the environ-
ment. While accepting that living systems are maintained in far-from-equilibrium
conditions, and are themselves dissipative, the organizational framework of the
sixties and seventies of the twentieth century emphasized that the distinctive
character of biological systems was to be found in their organization rather than in
their physical properties.
The other limit is that the notion of organizational closure was meant to provide
general theoretical foundations for notions such as life and even cognition, inter-
preted as a biologically rooted phenomenon common to all organisms (Piaget,
1967; Maturana & Varela, 1980). In this perspective, closure plays the role of
a general explanans from which a number of important implications about living
systems could be developed. However, this early work puts considerably less effort
into providing a detailed characterization of closure. For these early studies, the
very organization of biological systems is not itself an explanandum; for that,
causal relations and details about how they are realized need to be fleshed out.
During the last decades, work on biological organization has increasingly
focused on addressing these limits. It has seen attempts to shift the focus from
foregrounding the circularity of construction of biological system to emphasiz-
ing the need to also consider the thermodynamic requirements of maintaining an
organized system far from equilibrium and to incorporate consideration of the
material realization of living systems (Ruiz-Mirazo & Moreno, 2004). While
doing so, it has developed conceptual tools to develop the notion of organizational
closure and to characterize the causal relations it entails.
8
In this view, organization is a key concept to understand biological systems and a theoretical
hypothesis to guide research. According to Mossio et al. (2016) it can even be considered as
a theoretical principle, that is, an a-priori overarching hypothesis that frames the intelligibility of
biological objects.
Departing from the traditional characterization of organizational closure and

inspired by the work of Pattee (1972) and Kauffman (2000), Moreno and
Mossio (2015) and Montévil and Mossio (2015) emphasize the thermodynam-
ics of organisms in a way that goes beyond the idea that organisms just need
matter and energy: Organisms must constrain energy into the establishment of
their own components. Organisms are far from equilibrium with their environ-
ments. Accordingly, they must perform work to build and repair their compo-
nents. To do this work, they must procure energy from the environment and
constrain it to construct and repair the components responsible for this activity
as well as the other components and the physical structure that houses them.
A pivotal role in accounting for this activity of living systems has been played
by the notion of constraint. Constraints are defined as structures that act as local
boundary conditions that enable specific processes and activities.9 A constraint
C can be defined as a material structure that harnesses a process P by reducing
its degrees of freedom so that:
(1) at a time-scale characteristic of P, C is locally unaffected by P;

(2) at this time-scale C exerts a causal role on P, that is, there is some
observable difference between free P, and P under the influence of
C (Mossio et al., 2013).
Constraints exert a distinctive causal power, which consists in limiting the range
of possible outcomes (degrees of freedom) of a process, thus making some
possibilities more likely: They are both limiting and enabling. It is an asymmet-
ric relationship inasmuch as a constraint is not part of the process it modifies,
and it is stable during the time scale in which the process takes place. Through
its activity, it canalizes a process towards outcomes that otherwise would be
extremely improbable or practically impossible. An example of constraint is
a pipe harnessing the flux of water from a pond so that it arrives to a tank located
at a given distance across some hills and a valley: a process that would not
occur, or not as efficiently, by diffusion alone. In this case, the constraint (i.e. the
pipe) reduces the degrees of freedom of processes or collections of elements
(the possible direction of movement of the molecules of water) in such a way
that they exhibit specific behaviors (it enables water molecules to flow in the
9
In classical mechanics, the term constraint stands for an asymmetrical relationship such as that
holding between boundary conditions and dynamics. When the behavior of the system is under-
specified, constraints constitute an alternative description that provides the missing specifications
(normally by decreasing degrees of freedom). The notion of constraints has always escaped
precise definition, besides the general acknowledgement of its role in providing additional
specifications to dynamics that otherwise would be insufficiently (or incorrectly) described.
The organizational approach, however, takes a different path, and characterizes constraints not
as descriptive artifices but in terms of the causal role played by specific structures within a system.
same direction). This constrained behavior can be used to perform some coher-
ent activity in the context of a system (such as water filling a tank or moving
the wheel of a water mill). A typical example of a biological constraint is the
activity of an enzyme, which catalyzes a reaction without being directly affected
by it at the time scale in which the reaction takes place. What an enzyme does in
its active site is to bind to substrate molecules and to hold them in place (i.e.
restricting their freedom of movement in space so that their reactive sites can
interact) in such a way that the processes of breaking or making of chemical
bonds can take place more easily, thus lowering the activation energy required
for the reaction between the substrates to take place.
Constraints harness processes, by specifying (at least part of) the conditions of
existence of those processes. The notion of constraint so formulated allows us
to distinguish between two orders of “causes” in natural systems: processes
and those constraints that make those processes possible. The relevance of
this definition lies in the fact that it allows us to describe not only the internal
dynamics of a system but also to take into consideration the conditions of
existence of these dynamics, in particular how in some cases they can be deter-
mined or affected by the activity of the system itself. An aspect of paramount
importance is that although constraints are not changed during the interval during
which they enable work to be done, they are themselves constructed over a
distinct time frame. They are the result of production processes, which in turn
require the presence of other constraints to be realized. By acting on those
processes responsible for the production of other constraints, constraints are
conditions of existence for them. The distinctive character of biological systems
is that they are capable of generating from within some of the (internal) con-
straints that are necessary for their own functioning and for harnessing their
internal dynamics (Moreno & Mossio, 2015). Some of these might be inherited
from those constructed in a parent organism (Mossio & Pontarotti, 2022), but
most are constructed by the organism itself during its lifespan.
This idea is captured by the notion of closure of constraints which has been
introduced as a way to flesh out the causal relations implicit in the original notion
of organizational closure (Montévil & Mossio, 2015). These causal relationships
between constraints and processes are represented in Figure 2. In order for
a biological system to maintain itself far from equilibrium with its environment,
for each component C4, that constrains a process in the system, at least one of the
boundary conditions necessary for its maintenance and production are dependent
on the activity of another constrain C2 in the system, whose maintenance and
existence directly or indirectly (through other constraints, e.g. C3) depends, in turn,
on C4. By doing so, these constraints realize a distinctive circular causal regime by
which they are organized in such a way that they are mutually dependent for their
Figure 2 An abstract representation of closure of constraints (Montévil &

Mossio, 2015, reproduced with permission from Elsevier). Straight arrows
represent production processes. Wavy arrows represent the action of constraints
C. A1–5 represents the material inputs of production processes, while B1
represents a generic material output of the system. According to this diagram,
constraint C2 is a necessary condition for the production of constraint C4 from
the material substrate A2. Constraint C4 is a necessary condition for the
production of constraint C3 from A4. C3, in turn, is a necessary condition for the
production of C2 from A3. So organized, the three constraints C2, C3, and C4
form a closed loop in which they are mutually dependent for their existence.
production and maintenance, and collectively contribute to the maintenance of the

conditions in which the whole network can persist. In virtue of realizing closure of
constraints, a living system is able to maintain its dynamical organization despite
the constant transformations and turnover at the level of components.
This framework is characterized by a distinctive approach to understanding and
explaining biological phenomena. It is primarily focused on current biological
systems, such as organisms, rather than historical phenomena such as the evolution
of lineages. It aims to explain the maintenance of living systems by studying their
physiology and behavior in order to understand how they are or can be maintained
here and now. In a living system, understood in terms of a causal regime of closure
of constraints, a multiplicity of constraints contributes in different ways to the
maintenance of their organization. To provide an explanation of a given phenom-
enon, one would need to identify the processes involved and the different con-
straints that make them possible, and how both processes and constraints contribute
to the maintenance of the system that harbors them.10 Let us think, for example, of
10
Cusimano and Sterner (2020) question the possibility of univocally operationalizing constraints
and consequently closure of constraints. They call for more examples to be analyzed to show
e
Food
tak source
up
od
Cardiovascular
Fo
systems
Liver cells
Digestive
system Fat
Glucose cells
Glycogenolyis
Gluconeogenesis
Transport
Glycogenesis
Fatty
acids Fat
glycerol
Muscle
cells
Glycogen
Figure 3 General representation of glucose uptake, distribution, and

transformation. Processes are represented by dashed arrows, metabolic
substrates by dashed circles, constraints by rectangular boxes and their activities
by full arrows. The digestive system includes the set of constraints responsible
for the uptake of food, including glucose, which is then distributed throughout
the body by another set of constraints, the cardiovascular system. Transporters
and enzymes in liver, fat, and muscle cells are the constraints responsible for
glucose uptake and metabolism (glycolysis, glycogenolysis, and
gluconeogenesis). All these constraints are produced and maintained by the
system. Figure reprinted from Bich et al. (2020) under Creative Commons
License (CC BY-SA 4.0).
the phenomenon of glucose uptake and transformation through the digestive

system in mammals (Figure 3, see Bich et al., 2020 for more details). One can
identify at least seven processes with the relative constraints acting on them: (1)
food uptake, constrained by the digestive system (the constraints involved are the
digestive tube, the digestive enzymes, and the epithelial cells that absorb glucose in
the intestine); (2) glucose distribution within the system through the bloodstream,
constrained by the vascular system; (3) glucose uptake by cells of different tissues,
otherwise. In their view, the attribution of closure would depend on the explanatory problem
addressed.
constrained by glucose transporters in the cell membrane; (4) intracellular glycoly-

sis, the breaking down of glucose molecules into pyruvate as part of the process of
production of ATP,11 a process constrained by intracellular enzymes; (5) glycogen-
esis, which consists of the transformation of glucose into glycogen for storage,
constrained mainly by enzymes in liver cells, striated muscles cells, and cells of the
white adipose tissue; (6) glycogenolysis, the transformation of stored glycogen into
glucose, constrained by enzymes in all cells that store glycogen; and (7) gluconeo-
genesis, constrained by enzymes in liver cells, which produce glucose anew
starting from amino acids, lipids, pyruvate, and lactate. Closure is realized by the
fact that each part acting as a constraint is also the product of metabolic biosyn-
thetic processes taking place within the system, and glucose is used as a source of
energy for running the metabolic processes of the system. As a result of these
activities, the system maintains itself.
The notion of closure of constraints constitutes a refined version of organiza-
tional closure in which different types of entities (constraints and processes) and
causal relations are made explicit. It focuses on the distinctive capability of
living systems to contribute to their own conditions of existence. It establishes
a generative dependence between components through a closed topology of
transformation processes in which internally produced components constitute
a subset of the conditions of existence for those processes. However, this
circularity at the level of constraints should not be confused with any cycle of
activities at the level of processes. Cycles are captured by a different circularity
that is also known as closure of processes or operational closure, which stands
for the recursion between the operations of the components of a system: a
closed network of operations in which all the actions of the components have
an effect inside the system. To realize closure of constraints, and therefore
a self-maintaining organization, what is important is not only that the results
of the activities of parts remain within the system, but that for any component its
production process can be traced within the system. The circularity realized by
closure of constraints encompasses not only the activities of the components but
their conditions of existence, provided by their participation in the organized
system they continuously realize. While the notion of cycle, or operational
closure, says nothing about the origin of the components, organizational closure
points to their internal generation as well as to the properties they need to satisfy
in order to contribute to self-production, that is, to be able to participate in
processes of production – transformation and degradation – of other compo-
nents. This is a feature that is not shared by other circular networks such as
abiotic water cycles or self-maintaining systems such as dissipative structures
11
The fundamental energy molecule used to power cellular activities.
like hurricanes and whirlwinds (see Mossio & Bich, 2017). These latter do not
produce their own components and do not determine the condition of exist-
ence of their processes, but are mostly and largely determined by external
boundary conditions, and emerge spontaneously under appropriate environ-
mental conditions.12
In the introduction I argued that to understand living organisms and their
capability of maintaining themselves despite the fragility of their components,
one needs to take into account two main closely interconnected features of
biological systems: self-production and self-regulation. In this section, I have
shown how self-production is accounted for in terms of organization by the
notion of closure of constraints. In the next section, I will extend this framework
and complete the theoretical picture by turning on self-regulation.
4 Reinterpreting Closure: From Basic Self-Maintenance

to Regulatory Control
This section addresses some of the limits of the notion of closure of constraint.
It discusses how the conceptual core of the organizational framework and the
notion of biological self-maintenance can be developed and improved by taking
into consideration not only self-production but also self-regulation as the two
fundamentally intertwined properties that are necessary to characterize bio-
logical systems. While the first is captured by the notion of closure of con-
straints, the second is accounted for by the notion of regulatory control.
As mentioned in the introductory section, a distinctive feature of biological
organisms is that to be alive, they need to engage in a variety of activities that allow
them to keep living. They do not just replace and repair their parts, but also modify
themselves and what they (and their parts) do based on their internal physiological
state and environmental conditions. However, current notions of closure and
organization have been focusing primarily on the mutual dependence between
functional components of biological systems (characterized as constraints) for their
production and repair, considered as the core foundation of the theoretical
12
Equating closure of constraints and cycles means overlooking the generative dimension and the
contribution to the conditions of existence of a system that characterize closure of constraints.
This may lead to putting together phenomena that are qualitatively different from an organiza-
tional point of view. An example of this conceptual confusion can be found in Garson’s
discussion of panic disorders as cases of self-maintaining organizations subject to closure
(Garson, 2017). He exploits such cases to criticize the organizational framework as too liberal,
insofar as it would include in a regime of closure phenomena that do not contribute to the
maintenance of the system. However, the example discussed is a case of cycle, more precisely of
a behavior that reinforces itself. Like in the case of an abiotic cycle, this self-reinforcing behavior
indeed exhibits circularity and feeds into itself. But it does so at the level of operations or
processes, not of the constraints that generate those operations and processes, which are instead
extrinsic to the phenomenon. Therefore, it does not realize closure.
framework (Montévil & Mossio, 2015). By doing so, this research line has tended
to assume that what characterizes the core organization of biological systems is the
causal regime of production of components (closure) which achieves self-
maintenance based on productive relationships alone. The causal regime of closure
has been understood as inherently stable, and the activity of its parts characterized
by regularity when not affected by potentially disruptive environmental perturba-
tions that cannot be compensated for by building new parts to replace those
damaged (Mossio et al., 2016).13 The implicit assumption underlying this idea is
that under invariant and not threatening environmental conditions, closure is
sufficient to account for biological self-maintenance and to capture the distinctive
features of biological organizations. The idea of regulation is considered as an
additional, not definitory, feature of biological organizations: a capacity employed
only in cases in which the system is subject to strong perturbations that risk
endangering its viability. I will argue that the role of regulatory control in biological
systems is instead deeper and concerns every activity carried out by biological
systems, not only those related to response to perturbations. We cannot think of
closure without also considering regulation.14
The notion of closure of constraints has the merit of having provided
a theoretical characterization of the dimension of self-production of biological
systems and its underlying causal regime, compatible with their thermodynamic
requirements (Moreno & Mossio, 2015). In such a way it has overcome some of
the shortcomings of previous accounts of biological organization such as the
theory of autopoiesis, which had reached an impasse for several decades,
notably due to their lack of causal details and the detachment from material
considerations (see also Bich & Bechtel, 2021, 2022a). However, by focusing
on production, repair, and replacement of components to characterize the causal
regime of biological systems, the basic notion of closure of constraints is still
too narrow to capture the distinctive features of biological organizations and
provide a theoretical understanding of them. This is due to three types of
problems, which concern, specifically, its biological grounding, the capability
to account for the integration between components, and for change (adaptive,
physiological, developmental, etc.).
13
“Organization enables the maintenance of constitutive constraints, beyond their characteristic
time scales, through the continuous reestablishment of their mutual dependences. In this respect,
one might describe the overall stability of closure as the result of a kind of ‘organizational
inertia’. Because of the network of mutual dependencies, biological organization tends to
remove variations affecting local constraints and to regenerate them in a fundamentally unaltered
form” (Mossio et al., 2016: 31–32).
14
As argued by Cornish-Bowden and Cardenas regarding different accounts of organizational
closure: “All of these incorporate the idea of circularity to some extent, but all of them fail to take
account of mechanisms of metabolic regulation, which we regard as crucial if an organism is to
avoid collapsing into a mass of unregulated reactions” (Cornish-Bowden & Cardenas, 2020: 1).
With regards to biological grounding, the notion of closure of constraints

selects from the set of relations realized in biological systems the generative
ones involved in the production of components. This operation allows one to
address and characterize with clarity the mutual dependence between produc-
tion process and those constraints responsible for them. However, this comes at
the price of abstracting away other essential relations. In actual biological
systems, the basic constraints involved in a regime of closure are not always
functioning, or functioning whenever their substrates and energy are available.
Their activities are constantly controlled: inhibited, activated, and modulated.
Let us think of some basic biological activities. The production of ATP from
glucose is not carried out constantly, but only when its level is low, and energy is
needed by the cell. Cells do not divide continuously, but they engage in division
only at some given moments. Neurons generate action potentials, but appro-
priate stimuli either increase or decrease the rate of firing. Even a fundamental
activity such as protein synthesis, responsible for the production of those con-
straints (such as enzymes) participating in the core regime of closure, is not
carried out all the time and for all proteins. It is inhibited or activated on the
basis of the needs of the cell. Just as a cell cannot carry out all possible activities
continuously and simultaneously, it does not synthesize all its possible proteins at
the same time and all the time, due to spatial and energetic limitations. These
examples show that to maintain itself, an organism needs to continuously modu-
late and coordinate the activities of its basic constraints that directly harness
thermodynamic processes, in such a way that they can realize a viable regime of
closure. When looking at each of the constraints involved in closure, one should
consider that whether, when and how they act on processes, is constantly subject
to other types of organizational conditions not captured in the abstract diagrams of
closure shown in Figures 2 and 3.
Let us consider the second problem: integration. Closure emphasizes the
mutual dependence between components for their production but does not
account for how their activities are also mutually dependent so that compo-
nents are integrated into a system that maintains itself as a cohesive whole. In
living systems, different parts or groups of parts provide different and specific
contributions to the functioning and maintenance of the system. Harboring
components capable of playing different tasks such as catalysis, transport,
compartmentalization, signaling, DNA transcription, translation, protein syn-
thesis, and so on, is a fundamental requirement for division of labor. However,
besides producing all these components and thus ensuring their presence
within the system, a cohesive integration between these different tasks is
only achieved when those different activities are orchestrated so that they
collectively contribute to the maintenance of the system. Only those activities
needed in the current situation need to be carried out. Moreover, some parts or
subsystems may work differently and with different requirements, which are
not always compatible. One example is photosynthesis and nitrogen fixation
in cyanobacterium Synechococcus discussed in the introduction: two mutually
exclusive processes that need to be carried out at different times. In other
cases, specific activities need to be carried out only when others have already
been completed or some specific requirements are satisfied. For this to happen,
the components’ activities need to be modulated in such a way that each
operates when needed and in a way that is compatible with the state of the
system and the activities of the other components while avoiding potential
conflicts.
Let us move to the third problem: change. Organization theorists have not
denied that there is variability and change in living organisms, but while a lot of
effort has been put into emphasizing the continuity of a biological organization
through a life cycle (Di Frisco & Mossio, 2020), change has been often screened
off from their accounts as extrinsic to a biological organization and not strictly
required for it to function. Some proponents of the organizational view have even
argued that organization and variation should be considered as two distinct
theoretical principles (Montévil et al., 2016; Mossio et al., 2016). In this view,
the biological organization that realizes closure is inherently stable, while vari-
ation is something that happens to this organization during ontogeny and evolu-
tion (through randomness, perturbations, mutations, etc.).15 Variation is regarded
as a source of noise: external to a biological organization and not required (or
employed) for its viable functioning. This is a problem for several reasons. As
argued by Bich and Bechtel (2022b), regularity and stability in the activity of
components are exceptions within living organisms. A living system coordinates
the activities of its components, modulates internal processes, and responds
adaptively to environmental variations. It can undergo drastic modification of
its basic organization such as during development (Bich & Skillings, 2023). The
activity of each basic constraint is continuously modulated according to the needs
of the organization, starting from those basic constraints involved in transcrip-
tion, translation, and protein synthesis, so that each activity is performed in ways
appropriate to the circumstances the system faces and its internal state. Change,
often radical, is at the core of the functioning of biological systems, and accounts
of biological organization need to address it. However, as argued by Bich et al.
(2016) closure alone would account only for a very limited type of change,
understood in terms of dynamic stability, a passive network property: The basic
15
Montevil et al. (2016) include contextuality among the sources of variation. However, as
explained in this section, closure alone does not exhibit this property as it does not account for
the system’s sensitivity to the context and capacity to modify itself accordingly.
regime of closure would simply “absorb” as a network the effects of a limited

set of perturbations or internal variations (such as lack or increase of supply,
damage to some components, etc.). It would do so by compensating for these
perturbations through internal reciprocal adjustments between tightly coupled
processes (e.g. through increased or decreased production of components to
replace damaged ones, increased rates of processes, variation in the amount of
supply metabolites consumed, etc.), while the whole dynamic is maintained in the
initial attractor, or it is pushed by the perturbation into a new stable attractor. The
focus on repair and replacement of parts, for example, emphasizes restoring the
organism to its stable condition. Dynamic stability cannot account for how at
different times, and depending on its internal state, that of the environment and
the availability of food, a living system modifies itself by modulating and fine-
tuning its own activities and also undergoes radical changes. This is especially
relevant if one considers that the system continuously shifts between different
types of metabolism enabled by distinct sets of enzymes, between a regime of cell
growth and one of cell division, between different directions of movement to look
for nutrients or avoid predators, and so on.
In sum, the notion of closure of constraints has emphasized how the parts of
a living system are produced, transformed, and repaired from within the system.
However, to remain viable, both to carry out those basic physiological activities
required to realize closure when and how they are needed, and to face changing
environments, biological organizations must also behave adaptively, changing
what activities they perform in ways appropriate to the circumstances they face.
Only by deploying such adaptive capacities can organisms integrate the activ-
ities of their components and counteract potentially destabilizing interactions
with the environment. In line with some insights anticipated by Piaget (1967),
Di Paolo (2005) and Bitbol and Luisi (2004) emphasized the importance
of developing the organizational framework, and specifically the notion of
autopoiesis, in this direction. To do so advocates of the organizational frame-
work have introduced into their account and developed the notion of regulatory
control, characterized as an activity carried out by a special type of constraints:
control constraints (Bich et al., 2016).
What is control? Control is generally understood in biology as the capability
to actively modify the dynamics of a system towards certain states in a given
situation (Rosen, 1970). Metabolic control, for example, is characterized as
a modification of the state of metabolism in response to signals (Fell, 1997).
Control implies an asymmetric interaction: There is a controller that acts upon
a controlled process, component, or subsystem. A system able to control itself,
such as a biological one, should be able to employ different control components
to modify its internal processes and the activities of its other components
depending on internal and external conditions. Within the organizational frame-

work, accounting for this kind of relation requires introducing a special type of
constraint. Most constraints are realized by structures that statically reduce the
degrees of freedom of the process they canalize. It is the case of a pipe in
artificial systems, of a semipermeable membrane or a simple enzyme in a
biological system. This may be sufficient to enable and harness a process.
Control, however, implies something more, that is, the capability of modulating
and coordinating the activities of the components of a system towards a certain
behavior or goal state. This cannot be achieved by means of static structural
constraints. As pointed out by early work by Howard Pattee (1972), control
requires a dynamic constraint that can actively select between different possible
outcomes or activities available in the process or component on which it
operates and modifies. This can be achieved, for example, when a constraint
enables or inhibits a process in the presence of signal molecules or specific
conditions in its surroundings. By operating in this way, control constraints do
not just reduce degrees of freedom once and for all, for example by restricting
the flow of fluid in one specific direction. Instead, they are sensitive to the state
of the system or the environment, and they modulate the controlled process or
the behavior of other constraints accordingly (Bich et al., 2016; Winning &
Bechtel, 2018).16
Control constraints are a special type of constraint that are dynamic and do
not operate on production or repair processes but on the activities of other
constraints: They are second-order constraints. In biological systems, control
constraints play a regulatory role as they do not just modify the activities of
other constraints on the basis of what they sense, but in doing so they
contribute to the maintenance of the organisms that produce and maintain
those very constraints. Let us consider a simple case of biological control
protein: a kinase protein. This protein is produced within the system, but
instead of contributing directly to the generation of other constraints in
the system (like metabolic enzymes and other basic constraints involved in
closure of constraints do), it phosphorylates other proteins (enzymes) thus
modifying their conformation and their activities (inhibiting, activating,
modulating them). However, a kinase does not do that every time it encounters
a given enzyme, but only under specific conditions. It changes its activation
status on the basis of the interaction with a ligand or a signal molecule at
a different site than the effector site (the one where it exerts its constraining
activity on enzymes) and modifies the activity of other constraints based on
such interaction.
16
See Section 7 for more details on Winning and Bechtel’s proposal.
Within the organizational framework, regulatory control entails an architec-

ture of constraints (Figure 4) that satisfies four main requirements: (1) some
constraints Rs are higher order because they modulate the activity of other
constraints instead of directly channeling metabolic processes (as first-order
constraints Cs described by closure do); (2) these regulatory control constraints
Rs are themselves made within the system through the activities of other
constraints Cs, hence subject to closure (otherwise the source of control
would be extrinsic to the system); (3) they must be sensitive to variations and
capable of performing different activities depending on what they sense;17 and
(4) by modifying the operations carried out by other constraints, these higher-
order constraints must contribute to the maintenance of the system.
To better illustrate the idea, let us consider a biological example of regulatory
control that induces changes in how metabolism is carried out depending on
the presence or absence of specific metabolites. Bacteria need the amino acid
tryptophan for their metabolism. They take this amino acid from the environment,
but they are also able to start producing it when it is not available from external
sources. They can modulate the production of tryptophan through the regulatory
control of the transcription step of the synthesis of the enzymes necessary to
synthesize the amino acid. The genes encoding for the five enzymes that contrib-
ute to the production of tryptophan (the first-order constraints C involved in the
regime of closure) are grouped together into one operon. A repressor protein (the
regulator R) exerts regulatory control upon the promoter of the operon. Two
molecules of this amino acid act as the signals that are necessary to activate the
repressor protein. In the presence of tryptophan, the repressor protein interacts
with two of these molecules, it is activated and binds to the promoter of the
operon. By doing so, it represses the synthesis of the enzymes responsible for the
metabolism of tryptophan and blocks the endogenous production of this amino
acid. In the absence of tryptophan, instead, the repressor protein is in an inhibited
state and does not bind to the promoter region of the operon. When the promoter
of the operon is unbound, the transcription of the operon can start and the cell can
synthesize the enzymes responsible for the production of the amino acid, which
can then be used in biosynthetic pathways within the bacterial cell.
17
The operation of a control constraint on other constraints depends on the conditions it senses.
This entails that the activity of the components used in regulatory control are not totally
determined by the processes that produce them, although their presence in the system depends
on those. They are operationally independent, or “dynamically decoupled,” from what they
control (Bich et al., 2016), in the sense that they exhibit some degrees of freedom that are not
specified by the dynamics of the controlled constraints. Otherwise, they would be fully con-
strained by the dynamics of metabolism and not free to respond to the conditions they sense and
act upon them. Such a local operational independence allows regulatory subsystems to modulate
other constraints in a relatively autonomous way.
Figure 4 General relational diagram of regulatory control as the activity

of second (or higher)-order constraints (Bich et al., 2016, reproduced with
permission from Springer Nature). Cs are constraints involved in the basic
regime of closure of constraints; Rs are regulatory control constraints; P is an
environmental perturbation. Rs are sensitive to P and modify the activities of Cs
accordingly. Gray lines represent production processes. Black lines represent
regulatory processes. Full arrows represent intra-system processes, dotted
arrows signal interactions that trigger the activation of Rs, and dashed arrows
interactive processes with the environment.18
Regulatory control, as employed in this case, is what allows biological systems

to modulate the activities of their components coherently with the internal state of
the organism and that of the environment. It is a fundamental requirement for the
realization and functioning of a causal regime of closure as much as closure is for
the production of regulatory constraints. For closure to be realized and to be
viable, the activity of each constraint C depends on the operations of at least one
regulatory constraint R, which in turn depends on C for its existence. As argued
earlier, the need for regulation arises not just as a response to environmental
perturbations, but also as a result of the fact that living systems possess multiple
capacities resulting from the constraints they build within themselves. In order for
living systems to succeed in building, repairing, and reproducing themselves,
18
For explanatory purposes, the diagram describes regulation in the context of interaction with
a changing environment represented by P, but it can be applied to regulatory phenomena based
on the detection of internal states.
they need to coordinate these capacities by regulating their activities so that

they are performed when and how they are required to accomplish these ends.
This provides a richer view of self-maintenance beyond self-production: Due to
regulatory control, organisms can select activities on the basis of what they sense
and in so doing they contribute to their own maintenance. By taking into account
both closure and regulation, one can characterize a biological organization as
consisting of different components integrated into a cohesive unit. These compo-
nents are related in such a way that they depend on one another for their own
production, maintenance, and also activity so that they collectively contribute to
maintaining the organization that harbors them.19
Including regulatory control in the organizational framework also provides
richer, more detailed and biologically grounded explanations of biological
phenomena. Let us go back to the example of glucose metabolism discussed
in the previous section and described in Figure 3. From the point of view of
closure, the main processes and constraints considered are those that uptake,
distribute, and consume glucose. An equally important aspect is how and when
glucose is used, transported inside cells, made available for metabolism or
stored. These activities depend on the energetic needs of the organisms for
movement and metabolism, and need to prevent high concentrations of glucose
in the bloodstream after feeding. To provide a more comprehensive explanation
of this phenomenon from an organizational perspective, one needs to consider,
besides basic processes and constraints, also the regulatory control constraints
involved and how they operate on the other constraints to maintain the system:
for example, by activating or inhibiting them or selecting between different
processes to be carried out under different conditions. In the example of glucose
regulation, the main sources of control constraints are pancreatic alpha and beta
cells (Figure 5, B). By sensing their intracellular levels of ATP (which depend
indirectly on the presence and concentration of glucose in the blood), they
release hormones. One is insulin, which (released by beta cells) directly modu-
lates glucose transport into cells and the transformation of glucose into glycogen
19
It is important to point out that regulatory constraints do not usually act individually on distinct
first-order constraints. Each biological activity is controlled by different constraints, so that the
system can modulate its activities by taking into consideration multiple internal and external
conditions, such as for example the availability of energy, the presence of nutrients, predators,
and toxins in the environment, the alternance of daylight and darkness, and so on. Moreover,
regulatory constraints can be controlled in turn by other regulatory constraints in the system and
there is ongoing crosstalk between them. A further step in characterizing biological organiza-
tions is to address how regulatory constraints interact and are themselves integrated. See Bechtel
and Bich (2021) and Bich and Bechtel (2022b) for a general discussion of this dimension of
biological organizations and Bich and Bechtel (2022a) and Bechtel and Bich (2023) for
a detailed analysis of two specific case studies: integrated regulation in the bacteria E. coli and
in the multicellular worm C. elegans, respectively.
Figure 5 Representation of the regulation of glucose metabolism in mammals

(Bich et al., 2020). The basic processes and constraints involved in glucose
metabolism appear as described in Figure 3. B. Second-order regulatory
constraints are represented by those boxes whose activities are represented by
double arrows. The conditions to which they are sensitive are represented by
<Xs>above the pertinent boxes. Regulatory constraints such as insulin and
glucagon modify glucose transport into the cell and intracellular glucose
metabolism. C. Higher-order regulatory constraints, such as the nervous system
and gut cells, operate on second-order constraints. Their activities are
represented by triple arrows. Figure reprinted from Bich et al. (2020) under
Creative Commons License (CC BY-SA 4.0).
to be stored in liver cells. The other is glucagon, released by alpha cells, which
activates the production of glucose from glycogen stored in the liver. These
activities are selected depending on the level of glucose in the bloodstream
(high or low respectively) and the energetic needs of the organism. In turn
(Figure 5, C), the secretive activities of pancreatic beta cells are controlled by
further higher-order control constraints in the system. These include the nervous
system and gut cells, which start stimulating the release of insulin before the
increase in glucose levels happens, when the mammal sees the food and the food
enters the digestive system, to anticipate and counteract more quickly the rise in
glucose concentration.
After having introduced and discussed the conceptual foundations of the
organizational framework and illustrated them through examples, in the next
two sections I discuss how this framework has been applied in philosophy and
biology.
5 Naturalizing Biological Teleology and Functions

The previous two sections have discussed the conceptual basis of the organiza-
tional framework: the intertwined notions of closure and regulation. We can now
move to address how this framework has been applied to ground and naturalize
two central notions in the philosophy of biology: teleology (Mossio & Bich,
2017) and function (Mossio et al., 2009; see also McLaughlin, 2001 and
Christensen & Bickhard, 2002).20 They represent two ways to account for how
living systems can be characterized as having goals. Teleology aims to explain
why and how goals can be ascribed to biological systems as wholes. For example,
let us think of nutrition. A living system as a whole can be said to have the goal of
procuring and absorbing the nutrients it needs to survive. Nutrition requires
a living system to seek food in its environment, move to catch it, then to ingest
and digest it, and to process the resulting nutrients to use them as building blocks
and energy sources or to store them, while expelling waste. Functions instead are
ascribed to parts or specific traits of those purposive systems. A classic example is
an organ such as the heart, whose function as part of a living system can be said to
be to pump blood around the body through the vascular system. The organiza-
tional framework naturalizes the notions of teleology and function in a different
way than most other accounts, by looking at the current organization of a
biological system, instead of its evolutionary history.
5.1 Organization and Teleology

A challenge faced by biology is to make sense of those biological phenomena
that take place in a way that is, or appears to be, oriented towards goals, to
understand what is distinctive of them and how they differ from similar phe-
nomena occurring in purely physical, chemical, and mechanical systems.21
Those latter consist of processes that converge to a specific end-state (or
process) from a range of initial conditions, such as a marble falling in a bowl,
or a chemical system that goes back to equilibrium after having been displaced
from it. They are described as oriented towards an end-state, and they can be
usually described dynamically in terms of attractors.
Tending towards an end-state, however, is different from having goals and
acting in order to achieve them. When we say that an animal is seeking food, we
seem to be saying more than that it is settling into an attractor. Having and
pursuing goals is what we usually attribute to living organisms based on our
20
These are two of the contributions of the organizational framework that have had more
philosophical impact, especially the account of biological functions.
21
For a more detailed discussion of these ideas see for example Mossio and Bich (2017) and
Dresow and Love (2023).
everyday experiences, when we observe how they act in such a way as to persist
in their changing and often challenging environments: from looking for food to
escaping predators. Biology, therefore, seems to harbor phenomena that are
goal-oriented in a more fundamental sense, when compared to the physico-
chemical domain. This idea of goals is captured by the notion of teleology, that
is, the explanation of phenomena by reference to the purpose they serve.
Teleological vocabulary is widespread in biology, for example, when talking
of several important notions such as the function of parts, or phenomena such as
physiological regulation, behavior, and so on. However, teleological phenom-
ena are not exclusive to biology. Other classes of systems, such as artifacts, can
be described as teleological. We ascribe goals to artifacts as tools, from without:
They have goals for a designer or for a user. Their goals are therefore extrinsic.
When we say that biological systems pursue goals, we are not doing it for the
same reasons we ascribe goals to artifacts. We do not usually ascribe goals to a
living system in terms of what we can do with it, unless we are using it as a tool
(e.g. when we use yeast to leaven bread and ferment alcoholic beverages). What
is different in the case of a living system is that goals play a role within the
system itself: We ascribe goals to a living system because what the system does
has some importance to the system itself. In this view, biological goals are
intrinsic.
The challenges of addressing biological teleology are multiple. One needs to
account for purposes and goals in a way that is scientifically grounded, by provid-
ing naturalized explanations. These explanations can be important in order to
understand why living systems behave in some ways and not others, and to ground
several notions, starting with functions. They also need to capture the distinctive
intrinsic teleological dimension of living systems, compared to the extrinsic one of
artifacts and to the directedness exhibited by some physical and chemical systems.
Biological teleology aims to explain the presence of a system in terms of
what it does. According to advocates of the organizational framework, accounts
of biological teleology such as the evolutionary and the organizational ones
share a common naturalization strategy, which relates teleology to the contri-
bution to the conditions of existence of a system: They both look for a circular
causal regime such that the conditions of existence of a biological entity can
be said – in a scientifically acceptable way – to depend on its own effects
(Mossio & Bich, 2017). In both cases, biological teleology is naturalized by
identifying the telos with the conditions of existence of the relevant system.
While sharing a common strategy, evolutionary, and organizational accounts
differ with respect to the regime responsible for the realization of this causal
circularity and what is the system that realizes it.
The organizational framework focuses on current systems as the grounds for

teleology and biological organization as the relevant causal regime in terms of
which to naturalize teleology. This constitutes a Kantian approach to teleology,
which develops Kant’s idea, provided in the Critique of Judgement (1790/1987),
that organisms can be characterized teleologically as “natural purposes,” that is,
systems in which the components exist for the whole they generate and the whole
exists for the components it produces and maintains.22 Specifically, the organiza-
tional framework focuses on how individual organisms maintain themselves and
survive in their environment. To address teleology, it appeals to the relationship
between conditions of existence of a biological entity and its own activity. By
doing so, it aims to establish a connection between organization and teleology
through the concept of self-determination (Mossio & Bich, 2017).
The theoretical starting point for understanding this relationship is the idea of
closure of constraints, analyzed in Section 3, according to which the components
of a biological system are mutually dependent insofar as they act as constraints for
the processes responsible for the production and maintenance of other compo-
nents in the system, on which in turn, they depend. One of the features of closure
is that by acting on those processes responsible for the production of other
constraints, constraints are conditions of existence for other constraints in the
systems. In doing so, each constraint contributes to the maintenance of (some of)
the conditions under which the whole network can exist. As a result, the whole
organization of constraints achieves self-determination as self-constraint:
a regime in which the conditions of existence of the constitutive constraints are
mutually determined within and by the organization itself.
This causal regime can ground teleology because it establishes a circular
relationship between the existence and activity of a living system. According to
this view, a living system is what it does – it is a cause and effect of itself.
Inasmuch as the effects of the activity of living systems contribute to establish-
ing and maintaining their own conditions of existence and those of their parts, it
can be said that the existence of the system and its parts depends on their effects.
This allows organizational theorists to ground teleology in an organization that
realizes a regime of closure of constraints, and to identify the intrinsic goal
(telos) of a living organism with the maintenance of the conditions of existence
on which the organization exerts a causal influence.
22
Kauffman (2000) and Weber and Varela (2002) are among the first to underline this Kantian
legacy. Gambarotto and Nahas (2022) distinguish two different types of Kantian approaches to
biological teleology: heuristic and naturalistic. The first considers Kant’s teleology as a heuristic
tool for producing explanations of biological phenomena. The second sees in Kant’s idea of
natural purposes a new way to think about biological systems that should be developed by
naturalizing teleology and turning it into a legitimate scientific concept. The organizational
account of teleology would belong to the second type of Kantian approach.
This account can address the challenges to biological teleology mentioned at the
beginning of this section. It can differentiate between the intrinsic teleology of
biological systems and the extrinsic teleology of artifacts. Biological teleology is
intrinsic because the circular relation between existence and activity takes place
within the system considered. In artifacts, instead, the telos is distinct from the
conditions of existence: The goal of a tool is not to maintain itself, although it has
something to do with its existence since it is designed for a certain use. In this view,
biological teleology can also be distinguished from the directionality exhibited,
among others, by physical systems. Whereas teleology depends on a circularity
between existence and activity, directionality consists in the convergence to an end-
state and can be relevantly captured in terms of equifinality. It is an effect of a given
causal regime, not also a cause.23
Evolutionary accounts of biological teleology (e.g. Millikan, 1989; Neander,
1991) – which are the most used in the philosophy of biology – take instead the
lineage as the grounds of teleology, and natural selection as the relevant causal
regime. Selection allows one to consider the history of organisms as teleological,
insofar as the existence of a type of trait can be explained by the fact that the
ancestors of the organisms carrying the trait survived due to having that trait. These
accounts characterize teleology etiologically, in terms of contributions of traits to
the survival of the ancestors of current organisms, so that biological goals are
characterized in terms of adaptation by natural selection (inasmuch as they con-
tribute to maintain the lineage). Advocates of the organizational perspective
criticize evolutionary accounts by arguing that they fall into a form of “epipheno-
menalism” (Christensen & Bickhard, 2002; Mossio et al., 2009; Mossio & Bich,
2017) in that they implicitly presuppose the existence of individual organisms able
to survive and reproduce in their environment, that is, on individual adaptive
organizations. Moreover, while maintaining themselves, organisms may pursue
ends that do not relate to past selection. Based on this criticism, the teleological
dimension of living organisms might not be considered as the result of natural
selection but rather as its condition (Gambarotto, 2023).24
23
This is another important distinction between the organizational framework and the cybernetic
approach discussed in Section 2. Cyberneticians, while attempting to identify phenomena
common to artificial and living systems, identify teleology with directionality, and the telos of
a subsystem with its end-state (Rosenblueth et al., 1943). They do so by focusing on individual
mechanisms or simple organizational motifs. However, by ignoring the relationship between
activity and existence of a system and the self-maintaining nature of biological organizations,
they cannot distinguish extrinsic from intrinsic teleology, that is, between cases in which
a mechanism or motif is built and employed by a designer/user or by the system itself (see
Jonas, 1953; Mossio & Bich, 2017; Sachs, 2023).
24
This does not mean that the organizational framework is pursuing a better or more fundamental
approach. This type of discussion would just assume the form of an endless “egg or chicken came
first” debate. Organizational and evolutionary approaches should be seen instead as complementary.
Evolutionary accounts focus on functions and traits. They look outside

organisms rather than inside of them to ground teleology, and they do so in
terms of natural selection. The organizational framework, instead, characterizes
biological systems as inherently teleological, which means that their own
activity is, in a fundamental sense, first and foremost oriented towards an end.
The organization of a living system is an intrinsically teleological causal regime
where the conditions of existence on which the organization exerts a causal
influence are the goal (telos) of the system. A distinctive feature and virtue
of this organism-centered view is indeed its focus on the system as a whole,
rather than just its parts or traits, and its characterization as intrinsically oriented
towards an end: “teleology is not restricted to biological functions but under-
stood as the intrinsic goal-directedness of whole organisms” (Nahas & Sachs,
2023: 2). By doing so, the organizational account provides the framework to
discuss teleology more generally as a feature of biological systems rather than
their traits or parts only.
The organizational approach, however, it is not the only non-evolutionary
approach to biological teleology focused on organisms. Other non-evolutionary
approaches include the so-called “behavioral approaches” (Nahas & Sachs,
2023). These assume teleology at the outset, and they use it to describe how
organisms interact with their environments. One example is represented by the
enactive approach, which follows a Hegelian rather than Kantian approach (see
Gambarotto & Mossio, 2024): It treats organisms as purposeful systems by
assuming they have a teleological organization, and focuses on describing their
behaviors. Another example is constituted by Denis Walsh’s approach, which
also assumes that organisms are teleological, and addresses evolutionary pro-
cesses in terms of goal-directed agents (Walsh, 2015). The main difference
between these approaches and the organizational one is that in them teleology
plays only the role of explanans and not also of explanandum. Their focus is not
on how self-maintenance is achieved and they do not aim to naturalize strictu
sensu teleology, but they employ the notion to explain and naturalize other
phenomena.
One of the features, and perhaps a limitation, of the organizational account
of teleology, which characterizes it in terms of contribution to establishing and
maintaining the conditions of existence of the system (i.e. idea that “the
system is what it does”), is that it is very minimal. The core idea is that the
system and its parts do what they do, or they and the system would not exist.
In a regime of basic closure (production of components), the effects of the
activity of the system are teleological in a minimal sense as they contribute
to establishing and maintaining its own conditions of existence. The basic
constraints involved in closure realize this regime. They do what they do, and
in so doing they contribute to the maintenance of the system. Developing

a minimalist account is useful in order to provide a basic philosophical and
theoretical grounding for the notion of teleology, a minimal common starting
point from which to consider a system as teleological. However, this may
constitute a limit if the minimal account is not employed as a stepstone
to building a richer view that can precisely account for more fundamental
features of biological systems and a wider range of phenomena. Living
systems are teleological not only because their parts operate and, as an effect,
contribute to maintaining the system. They also perform their activities when
and in such a way as to maintain the system. A teleological regime is not just
realized or not depending on whether the components of a system are working.
It can also be realized in different ways depending on the circumstances.
Organisms, while maintaining themselves, select between different available
courses of action on the basis of their needs and environmental conditions.
This more active feature of biological systems is not explicitly captured
by the minimal notion of organizational teleology developed in terms of
self-determination by Mossio and Bich (2017). The reason for this lies in
the fact that this notion is grounded in the notion of closure, which focuses
on self-production. Therefore, the minimal notion of organizational teleology
does not account for the variability of the behaviors of parts, how they are
integrated and orchestrated, and how they allow the system to change. As
a consequence, it cannot distinguish between minimal and active purposefulness.
To better capture the distinctive teleological dimension of biological organ-
izations, one needs to consider how organisms not only establish but actively
exert a control over the way they contribute to their own conditions of
existence (i.e. over the activity of basic productive constraints). As with
regards to closure, one way to enrich the organizational account of the
teleology and to include these fundamental purposeful activities is to take
into account regulatory control. As shown in Section 4, control constraints
allow a biological system to evaluate alternative modes of operation given the
state of the system and the environment. Depending on that evaluation they
modulate the activity of basic productive constraints in such a way that the
system as a whole maintains itself. A regulated biological organization,
therefore, does not only establish its own conditions of existence, as described
by the notion of closure of constraints. It also operates on how these condi-
tions of existence are realized. The main difference between basic and regu-
lated closure is that the first includes activities that have the effect of
maintaining the system, and the second establishes a causal regime that
modulates these activities. It selects between its possible actions and takes
the selected actions to maintain itself. Including regulation enriches the
organizational account of teleology by treating a living organism not only as

being teleological but also as operating teleologically (Bich, 2024a).25
5.2 Organization and Functions

The account of teleology just discussed provides a philosophical grounding for
the organizational account of biological functions. Accounts of biological
functions focus on the role of specific traits or parts rather than on the biological
system as a whole. According to the organizational framework, in a system that
realizes a teleological regime of self-determination, it is possible to ascribe
functions to parts. The organizational account of functions was inspired by the
work of McLaughlin (2001) and Christensen and Bickhard (2002), among
others, and developed in the details by Mossio et al. (2009). The specificity of
these contributions is that they relate functions to contributions to the mainten-
ance of the system to which they belong. I will focus in particular on the
formulation of this account by Mossio et al. (2009), as it is built on the
theoretical framework discussed in the previous sections and complements
the account of teleology analyzed in Section 5.1.
The core idea of the organizational account of functions is that in a regime of
self-maintenance that realizes closure of constraints and, therefore, is inherently
teleological, functional attributions are justified in terms of the contributions of
traits to the maintenance of the system that harbors and produces them. More
specifically, on this account, a trait or part T exerts a biological function if and
only if the following conditions are satisfied (Mossio et al., 2009; Saborido
et al., 2011):
(1) The organization of the system S to which T belongs realizes closure of

constraints (it is a self-maintaining biological organization);
(2) T is produced and maintained under some constraints exerted by the
organization of S;
(3) T contributes to the maintenance of the organization of S;
(4) S is organizationally differentiated, that is, there are differential contri-
butions to the maintenance of its organization, which allow for the
identification of functions.
25
Recent work by González de Prado and Saborido (2023) follows a different path, ascribing to
regulation a non-organizational teleological dimension that is different from the contribution to
self-maintenance and possibly complementary to it. It is a version of teleological accounts
grounded in biological selection. This work takes a special perspective on regulation, as it
focuses on one of the definitory features of regulation (their activity: the first requirement
discussed in Section 4) and analyzes regulation detached from the biological organization that
harbors it. It argues that regulatory constraints are teleological themselves because they select
between different behaviors of basic constraints.
In a system that realizes a self-determining teleological organization, where the

telos of the system is understood in terms of self-maintenance, a biological
function is therefore understood as a contribution of a part to the maintenance of
the organization (e.g. a living cell) that, in turn, contributes to producing and
maintaining the part itself (Mossio et al., 2009).26 An important implication
of this account is that given that self-maintenance is characterized in terms
of closure of constraints, the functional parts of this type of organization, which
contribute to its self-maintenance, coincide with the constraints subject to
closure. Hence, for a biological system, the set of constraints subject to closure
is the set of biological functions: The basic constraints involved in the causal
regime of self-production can be characterized as first-order functions, while
regulatory constraints as second or higher-order functions (Bich et al., 2016).
All systems that satisfy these conditions can harbor biological functions. In
this view, teleology and function would be linked to any kind of biological
system that can be expressed in terms of this type of organization, rather than to
the more restrictive concept of organism. In principle this account could attri-
bute functions to supra-organismal systems such as ecosystems (Nunes-Neto
et al., 2014) or symbiotic associations (Bich, 2019), if they can be shown to be
organizationally closed. It provides a general framework for biological tele-
ology and functions that can in principle account for a wide range of biological
systems coming out of interactions between living organisms.
The organizational account of functions is a framework that can be situated in
the middle between the two main traditional accounts of biological functions,
the dispositional and the etiological ones. It aims to keep their virtues while
avoiding the issues usually associated with them. Dispositional accounts
(Cummings, 1975) identify the function of a component with its causal role
within a larger system. However, they do not provide a normative basis for
distinguishing which among many causal effects to count as the function of
a component. Like dispositional accounts, the organizational account focuses
on the role of components in a system but it characterizes this system in
teleological terms, thus grounding principled functional attributions. The etio-
logical approaches based on evolutionary selected effects focus on the origin
and explain the presence of functional traits by appealing to their evolutionary
history. They identify as functions those effects of components that led the
ancestors of current organisms to be selected (Millikan, 1989; Neander, 1991).
They face several problems, including that previous adaptations may no longer
be functional for the organism, or traits that are currently contributing to the
26
For a proposal on how to address not only functions but also biological malfunctions in
organizational terms, see Saborido and Moreno (2015).
survival of an organism might not have been previously selected as adaptations.

The organizational framework also aims to explain the presence and origin of
a trait, but it does so in terms of its production, maintenance and the role it plays
within a biological system. Therefore, it is not subject to the problems confront-
ing evolutionary accounts of function. Moreover, as argued by Frick et al.
(2019), it might have some practical advantages. By adopting an etiological
evolutionary account, one should expect that when scientists identify a function,
they do so on the basis of evolutionary evidence. However, this is not what
typically happens in scientific practice. When biologists characterize a function,
they may do it on the basis of things happening at the present time within an
organism, and only afterwards attempt to reconstruct its evolutionary past.
Within the organizational framework, functional roles are usually attributed
to physiological traits involved in the maintenance of the organism. One issue
faced by this framework concerns cross-generation functions, that is, those
functions, such as reproduction, which do not directly or explicitly contribute
to the maintenance of the current organization of a biological system. To address
this concern, advocates of the organizational framework have provided a
possible yet controversial way to functionally ground cross-generation func-
tions such as reproduction (Saborido et al., 2011, see also Mossio & Pontarotti,
2022). In their view, reproductive traits are functional because they are pro-
duced by the biological organization of the parents at some point in their life
cycle, and they contribute to reestablishing that very organization in the off-
spring. The main idea is that if a given system possesses an organization
realizing closure because of its causal and material connection with a previous
system possessing the same organization, then both systems can be considered
as temporal instances of the same encompassing organization. Based on this
idea, the solution proposed by Saborido et al. (2011) is that a reproductive
function is subject to a regime closure of constraints within a self-maintaining
organization whose extension in time goes beyond the lifespan of an individual
organism. According to this view, one could say that the sperm cell has the
function of inseminating the ovum, because by inseminating the ovum the trait
contributes to the replacement of the systems that are part of an organization,
which in turn exerts several constraints under which the semen is produced and
maintained in time. This account of cross-generation function has raised criti-
cisms, for example, by Artiga and Martinez (2016), who argue that the organ-
izational account is ultimately an etiological account. In a reply to Artiga and
Martinez’s paper, Mossio and Saborido (2016) agree that the organizational
account is compatible with etiological accounts in general, because it also aims
to explain the origin and presence of a trait. However, they argue, it constitutes
an alternative to those etiological accounts that are based on evolutionary
considerations, because it provides a different grounding for functional attribu-

tions: maintenance of an organization through generations rather than evolution
by natural selection.
6 Interpreting Biological Phenomena through the Lens

of Organization
This section addresses attempts to apply the organizational framework to
investigate and explain biological phenomena. The common feature of these
endeavors is that they address biological phenomena by foregrounding the
living systems that realize them. They do so by considering these phenomena
within the context of organized cohesive wholes that maintain themselves. This
framework has been applied in this way to phenomena such as evolutionary drift
(Maturana & Varela, 1987; Maturana & Mpodozis, 2000), multicellularity
(Arnellos et al., 2014; Bich et al., 2019; Bechtel & Bich, 2023; Bich, 2024b),
intracellular signaling in bacteria (Bich & Bechtel, 2022a), heredity (Mossio &
Pontarotti, 2022), development (Montévil et al., 2016; Bich & Skillings, 2023),
collective biological organizations (Canciani et al., 2019; Militello et al., 2021),
minimal biological agency (Barandiaran et al., 2009; Moreno, 2018), multicel-
lular agency (Arnellos & Moreno, 2015), and ecological systems (Nunes-Neto
et al., 2014). For reasons of space not all the biological phenomena addressed by
the organizational account can be discussed here. I will focus instead on two
cases that exemplify some of the core features of this framework and show how
it can be fruitfully applied in biology. The first example is work on origins of
life, which perfectly illustrates the focus on the minimal biological organization
and the related idea of multiple realizability. The second is biological commu-
nication, which represents a direct application of the organizational account of
functions to a biological case study.
6.1 Origins of Life

For several decades, origins of life has been the main field of application of the
organizational framework in biology, through work based on the notion of
autopoiesis (Luisi, 2006). This has been facilitated by two closely interrelated
features of this theoretical framework (Bich & Damiano, 2007). The first is the
focus on organization as the minimal set of relations common to all living
organisms, which makes it a good theoretical tool to investigate minimal life or
the steps towards it (Ruiz-Mirazo & Moreno, 2004). The second is the emphasis
on organization rather than intrinsic properties of components, which supports
the idea of multiple realizability of living systems. To study the origins of life,
scientists cannot rely on traces or fossils of prebiotic systems. Nor they can
totally rely on knowledge of present-day biological systems to infer the features

of precursors of current living systems, because early physical and ecological
conditions are not well known. Moreover, at early steps in prebiotic evolution
there could have been takeovers by new forms of proto-life, replacing older
ones and thus also generating new ecological relationships. This scenario might
seem to preclude the possibility of a scientific investigation of the previous steps
towards life. However, the idea of multiple realizability allows scientists such
as synthetic biologists to attempt to create today possible forms of prebiotic
entities without necessarily claiming that they are the true antecedents of
contemporary life. Scientists, thus, can investigate the prebiotic world by experi-
menting with a variety of biologically plausible prebiotic components that are not
necessarily the same components of full-fledged living organisms, and to use
them to produce models of possible precursors of life. These results, by analogy,
can provide useful information about a subset of the general constraints that
prebiotic evolution had to satisfy. As such, they do allow scientists to formulate
some hypothetical scenarios about the origins of life.
The starting idea of an organizational approach to the origins of life is that
biological systems are individuated through their own activities. Advocates of the
early organizational framework such as Maturana and Varela (Varela et al., 1974)
put emphasis on the presence of a physical border, a membrane generated by the
system itself. In the context of research on the origins of life, which was mostly
focused on the emergence of replication and reproduction as the conditions for
biological evolution, the introduction of the notion of autopoiesis has provided
the theoretical basis for a shift in attention towards properties of compartments
(Hanczyc, 2009). However, an organizational approach does not just emphasize
the importance of experimenting with compartments, but rather the need to
integrate metabolism (self-production) and compartmentation (self-distinction
from the medium and control over concentrations and exchanges) into a spatially
individuated organized system capable of achieving self-maintenance as a whole
(Luisi, 1993). This requires a shift from a focus on individual components to one
on “protocells” as coherent unities (spherical collections of lipids) with internal
processes, proposed as the infrastructures for the origins of life.27
Already in the early years of the organizational tradition and of Artificial Life,
Francisco Varela introduced the definition of an autopoietic system together with
a computational model of the generation and maintenance of a compartment
(Varela et al., 1974). One of the first isolated attempts to realize biochemical
laboratory experiments based on this theoretical framework was carried out by
Gloria Guiloff, a graduate student in Maturana’s laboratory at the Universidad de
27
See Rasmussen et al. (2008) for a general picture of work on protocells.
Figure 6 The chemical model of the “minimal autopoietic unit” (from Zepik
et al., 2001, reproduced with permission from John Wiley & Sons, Inc).
Chile, although without success (Guiloff, 1981). However, it is with the work of
Pier Luigi Luisi’s group in Zurich first and later in Rome, that these ideas gave rise
to a full-fledged research program on origins of life (Stano & Luisi, 2016). Luisi
adopted a definition of biological organization based on the work of Maturana and
Varela, but minimal enough to be applicable to prebiotic chemical systems: “a
system which is spatially defined by a semipermeable compartment of its own
making, and which is self-sustaining by transforming external energy/nutrients by
its own process of component production” (Luisi, 1998: 619).
Several experiments inspired by this autopoietic definition have been per-
formed by Luisi’s group over the decades. A particularly illustrative example is
Zepik et al.’s (2001) chemical model of minimal autopoietic unity (Figure 6).
This model is designed to explore the relationship between compartments and
self-maintenance in prebiotic systems. It describes a compartmentalized chem-
ical system composed of an oleate vesicle, a spherical bilayer structure made
of lipids, that hosts an aqueous core. The boundary of the vesicle, the bilayer
lipidic structure, is maintained by the continuous replacement of decayed oleic
acid components on the surface (P in the figure) by new components (S in the
figure) produced through the hydrolysis of a precursor A. The originality of the
model does not consist just in the synthesis of the vesicle but in that it combines
a reaction of production of membrane components S from A, with a competitive
decay reaction which transforms S into the waste product P. By balancing the
rates of the two reactions the chemical model can account for different and
biologically interesting kinetic modes such as homeostasis (when the rates are
equal), growth (when production is faster than decay, eventually leading to
division and reproduction), and death (when decay is faster than production).
The minimal chemical model allows for the exploration of different possible
dynamic regimes by modulation of these reactions. By focusing on the dynamic
organization of simple vesicles, it does not aim to identify what were the actual
chemical components of prebiotic systems during the origins of life. It aims
instead to provide proof of principle for experimental investigation of possible
self-maintaining precursors of current living systems, aimed at achieving a
better understanding of the conditions for the emergence of prebiotic
organizations.
It is worth mentioning that although these pioneering experiments rely on the
idea that living systems share a common self-maintaining organization and aim
to discover its minimal requirements, they focus more on fleshing out properties
of coherent dynamic wholes than on building organized systems with different
parts playing different roles. This is due in great part to technical limitations,
and the need to realize reliable compartmentalized systems such as protocells
before turning the attention to establishing internal metabolic processes (see
Ruiz-Mirazo et al., 2014 for a discussion). The next step consists in designing
a basic internal metabolism capable of sustaining itself and synthesizing both
the lipids that constitute the membranes of the vesicles and the peptides (short
chains of amino acids) to be incorporated into these membranes so as to provide
channels through which specific molecules are admitted or expelled from the
cell. However, protocell designers recognize also that they must build mechan-
isms that control the behavior of those channels so as to avoid osmotic crises
and to ensure that materials enter and are expelled consistently with the needs of
metabolism. More recent work has gone in this direction by providing more
sophisticated chemical and computational models of self-maintaining compart-
ments with differentiated components. Examples are models of membranes
with simple channels, made of internally produced peptides, that allow the
diffusion of metabolites in and out of a vesicle (Ruiz-Mirazo & Mavelli,
2007; Shirt-Ediss et al., 2013). Other work has investigated the possibilities
of modeling spatially constrained proto metabolism (Lauber et al., 2023).
6.2 Biological Communication

Let us now move to communication, an example of application of the organiza-
tional account of functions to understand a biological phenomenon, carried out
by Ramiro Frick and collaborators (Frick et al., 2019). Communication is a very
widespread and diversified phenomenon in biology. Bacteria exchange signals
and coordinate their activities – for example, through quorum sensing mechan-
isms like those described in Section 1. When damaged, plants release volatile
molecules that are detectable by neighboring plants, which in turn activate
preventive defense mechanisms against herbivores. Animals such as mammals
or birds can make use of vocalizations. At the edges of biology, communication
may include attempts by synthetic biologists to design artificial protocells

capable of triggering signaling response in living cells for medical and techno-
logical applications (Rampioni et al., 2014).
Quoting Thom Scott-Phillips, “on first appearances, these phenomena have
little in common. Yet they must presumably share something, if we are happy to
identify them all as instances of communication” (Scott-Phillips, 2009: 245).
Theoretical accounts of biological communication aim to identify and unify into
a coherent framework the common elements that allow scientists to account for
all these phenomena in terms of communication. Besides unification of different
phenomena under a common theoretical notion, accounts of communication
also need to satisfy two further requirements (Bich & Frick, 2018). The first is
an operationability requirement: They should be applicable in science and
capable of grounding and orienting theoretical and experimental research on
communication in biology as well as in related disciplines such as synthetic
biology, where they should also offer guidelines for the evaluation of results.
The second is a demarcation requirement: An account of communication should
be able to provide conceptual tools to discriminate between communicative and
other biological interactions. In fact, not all nonphysical interactions between
biological systems that trigger behavioral changes are instances of communica-
tion. Let us consider, for example, a lion chasing a gazelle. The lion sees the
gazelle and starts chasing it. The gazelle hears the lion approaching and starts
running in order to escape it. Then the lion adjusts its course to the new path and
speed of the gazelle, and so on. This is a case of interaction in which two biological
systems realize a form of coordinated behavior in which actions in one system
trigger changes in the behavior of the other, but we would not say that the noise
made by the lion is a signal that communicates to the gazelle that it needs to escape.
Intuitively, this is not a case of communication.
The two accounts of communication most widely adopted in biology are the
“information” and “influence” approaches. According to the information-based
approach, communication can be defined in terms of information transfer from
a sender to a receiver by means of a signal. Although the characterization of
communication in terms of information is widespread, the very concept of
“information” is controversial due to the lack of agreement on a common char-
acterization of information, and the demanding theoretical assumptions on
notions such as information and representations (Kalkman, 2019). Moreover,
this approach puts more emphasis on the informational content of the signal, and
less on the role of the system that realizes, harbors, maintains, and employs the
mechanisms necessary to engage in communicative interactions. The competing
account is based on the notion of influence. According to it, communication can
be defined in terms of a signal emitted by a sender: (1) whose presence triggers
some response in the receiver; and (2) that has the function of triggering such
a response. The influence account emphasizes the operations of the systems
involved in communication and does not carry the same heavy theoretical
baggage as the information account. Most importantly for organizational theorists
it grounds communication in the notion of function. The functional dimension is
essential. It provides a criterion to discriminate between cases of communication
and other interactions. Going back to the example of the lion-gazelle system, for
example, one could not say that the noise made by the lion has the function of
triggering the escape of the gazelle. Therefore, according to this view, this is not
a case of communication.
The notion of communication as influence was introduced by Dawkins and
Krebs (1978) within an evolutionary framework. To ground their account, they
adopt an evolutionary-etiological account of biological functions. In their view,
the functionality of a signal for the sender is interpreted in terms of adaptations:
The ability to send a signal is a functional trait because it allowed the ancestors of
the sender to survive and reproduce at a higher rate than other individuals lacking
this trait. Formulated in terms of etiological functions, however, this account
exhibits several issues. This is due to the fact that it defines an interaction between
organisms as communicative only in virtue of a history of selection of similar
patterns of interactions realized by their ancestors. In doing so, the influence
account risks conflating two different questions: a question about what commu-
nication is and how it takes place in a system under study, with a question about
how the communicative interaction originated in the first place. As remarked by
Di Paolo (1999: 20–21), this approach implies that any interaction between
organisms, “no matter how ritualized or similar to known cases of communica-
tion,” cannot be considered to be an instance of communication until its selective
history has been advanced. This is problematic from the point of view of scientific
practice inasmuch as many biologists are usually interested in the phenomenon
of communication they are currently observing, rather than its evolutionary
history. The latter is usually investigated only after the trait in question has already
been described as a signal and the interaction that it mediates as an instance of
communication. Moreover, this account would exclude from the set of commu-
nicative interactions those that are the result of exaptations, even if they exhibit
the same phenomenology as those interactions that are the result of selection.
Importantly, the characterization of communication as a product of natural selec-
tion rules out a priori the very possibility of an artificial, non-evolved communi-
cation system, making this approach useless in contexts like synthetic biology
where communication is playing an increasingly important role.
A possible solution to these problems, as advocated by Frick et al. (2019), is
to reframe the influence approach and the notion of functional influence in terms
of the current organization of the system rather than in terms of evolutionary

adaptations. This operation can be done by adopting the organizational account
of biological functions, according to which, as discussed in Section 5, functions
are understood as a contribution of a trait to the maintenance of a biological
organization that, in turn, contributes to producing and maintaining the trait
itself. By adopting this account, the influence approach to biological communi-
cation can be reframed in organizational terms. In this view, to say that a signal
is functional means that it contributes to the maintenance of the current organ-
ization of the sender, without necessarily appealing to its evolutionary history.
Given two systems, A and B, realizing regulated closure of constraints, according
to an organizational-influence account communication implies that (1) a receiver
B responds to a signal emitted by the sender A, and (2) that a signal is a sender’s
trait that by triggering some response in a receiver B, contributes to maintain the
organization of A that, in turn, is responsible to produce and maintain the signal
trait itself.
More specifically, understood in organizational terms, communication relies
on the operations of sensory-effector regulatory mechanisms in the two part-
ners, realized by control constraints. Sensors of regulatory mechanisms of
the sender A are triggered by internal or environmental conditions, and their
effectors activate the emission of a signal by A. The signal triggers a regulatory
response in the receiver B, which changes its behavior. The new behavior of B is
functional for the sender in the sense that it contributes to the maintenance of
A in the context that activated the regulatory action in A. If a pattern of
interaction is observed that realizes this type of closed loop, it can be identified
as an instance of communication (Figure 7). A simple example is a hungry cub
calling for its mother, which responds by bringing food. The cub (the sender A)
maintains itself by recruiting a functional contribution from the mother, the
receiver B. The same can be said of bacteria interacting through quorum sensing
mechanisms while colonizing a surface and forming a biofilm and, in principle,
of artificial systems if they satisfy the requirements for functional influence.28
The organizational-influence account satisfies the operationability requirement
mentioned earlier, as it provides a naturalized notion of communication that can
be applied directly to scientific practice. It also satisfies the demarcation require-
ment inasmuch as it provides tools to discriminate between interactions that are
communicative and those that are not. A virtue of this account derives from its
focus on current systems, typical of the organizational framework. It makes it
possible to identify and to study in the field or in experimental settings as
28
See Frick et al. (2019) and Bich and Frick (2018) for a detailed discussion of case studies from
biology and synthetic biology.
Figure 7 Communication between biological systems A and B. The dotted line

represents the conditions triggering regulatory actions in the sender A. The
dashed line represents the signal emitted by A on the basis of its regulatory
activity. The full line represents a response by B that is functional for A.
instances of communication phenomena that realize interactive patterns typical of
signaling interactions despite not being the result of evolutionary adaptations or
without the need to reconstruct their evolutionary history.
7 Bridging Philosophical Frameworks: Organization

and Mechanisms
This section aims to situate the organizational framework within a wider philo-
sophical context by discussing the relationship with new mechanism, another
framework in the philosophy of biology that refers to organization to explain
biological phenomena. New mechanism appeals to how components of a mechan-
ism are organized so that their activities produce a phenomenon. This is a different
approach than the one pursued by the organizational framework, which instead
focuses on how the components of a biological system are organized not within
a mechanism but in such a way that they contribute to the maintenance of the living
systems that produce them. These two perspectives each identify a form of
organization that is employed in living organisms and deploy different decompos-
ition strategies to develop explanations of biological phenomena. This section
discusses the differences between these frameworks by arguing that they are not
incompatible but complementary. It then shows that biological explanations can
benefit from establishing conceptual bridges between the two.29
Traditionally, the organizational framework, with its emphasis on consider-
ing the living system as a whole and on abstract relations over material compo-
nents, has been regarded a priori as in opposition to mechanistic accounts and
29
For the detailed discussion of the relationship between organizational framework and new
mechanism see Bich and Bechtel (2021, 2022b). See also Gambarotto (2023) for a discussion
focused on teleology.
explanations of biological phenomena. The reason is attributed to the fact that

mechanistic explanations are reductionistic and focused on the properties of
the components. The roots of this attitude lie, in part, in the historical baggage of
the opposition between seventeenth-century mechanism and various vitalist,
holist, organicist, and systemic approaches that during the subsequent centuries
reacted to the application in biology of the Cartesian or LaMettrian conceptions,
which regarded animals and humans as machines (see e.g. Letelier et al., 2011;
Wolfe, 2014). During the development of the organizational framework, an
important role in this regard was played by Rosen’s criticism of a specific notion
of mechanism, that of Newtonian mechanics. According to Rosen (1985, 1991),
Newtonian mechanism tends to separate and isolate different types of causes, and
describes systems in terms of sequences of changes of states. As a consequence, it
cannot account for causal circularities where components can be both material
causes (substrates and products of transformations processes) and efficient causes
(carrying out the transformation processes like enzymes do).
What about new mechanism? This framework views biological phenomena as
the products of mechanisms that behave as they do because of their constitution
(Machamer et al., 2000; Glennan, 2002; Bechtel & Abrahamsen, 2005). At first
sight, thus, the focus on “constitution” might support an opposition between the
organizational framework and new mechanism. However, new mechanism does
not overlook or discard organization. It defines a mechanism relative to
a phenomenon as consisting of the parts whose activities and interactions are
organized in such a way that they are responsible for the phenomenon: It is not
just a question of composition. It is true that mechanisms are constituted by
distinguishable parts that perform different operations, but such operations need
to be connected in order to bring about a phenomenon. Organization is what
determines which parts interact with which other parts, in what order, and how
they contribute to the behavior of whole mechanisms, and so on (see Glennan,
2017 for examples).
Much of the discussion of organization among new mechanists has focused on
ways components can be put together into mechanisms. Much effort has been
directed on explaining how components and activities are arranged so as to realize
what Machamer et al. (2000) refer to as “productive continuity”, whereby the
output of each component but the last is taken up by at least one other, thus
connecting the parts into a whole. However, accounts of mechanisms differ with
respect to the degree of emphasis put on organization. Machamer et al. (2000)
emphasize progression from start to termination conditions, but they acknowledge
that there can be bifurcations and cycles in between. Glennan (2002: 344)
stresses the importance of “direct, invariant, change-relating generalizations”
in characterizing the interactions between parts. In Bechtel and Abrahamsen’s
account of mechanism, organization plays a more decisive role. In their

definition of mechanism (2005) organization is more than the connection
between the operations of parts, as they emphasize that these activities need
to be “orchestrated” within the context of the mechanism. They also draw
attention to the fact that biological mechanisms often exhibit nonsequential
organization (Bechtel & Abrahamsen, 2009). In advancing their accounts,
however, new mechanists have had little to say about whole living systems.
Mechanisms are understood as organized parts that together perform the
activities required to generate the phenomenon. The focus is on phenomena –
with mechanisms construed as each responsible for one phenomenon – not on
the role these phenomena and the corresponding mechanisms play in the
context of the system that harbors them, benefits from them, and is responsible
for their existence. Living systems seem to be treated as simply collections of
mechanisms, leaving unexplored the question about how they are integrated
into the system.
The organizational framework, on the contrary, does not start with a specific
biological phenomenon, but with a biological system characterized as capable
of producing its own components and maintaining itself far from equilibrium
with its environment. It appeals to the (internal) organization of the system to
account for this capacity. Organization here refers to the way production and
transformation processes are connected so that they are able to synthesize the
components that realize them by using energy and matter from the environment.
The organizational framework differs from mechanistic accounts in that it
emphasizes the relations that contribute to the existence and maintenance of
the system as whole (and of its parts), rather than the generation of a specific
phenomenon. Phenomena – such as the example of glucose metabolism and
regulation in mammals discussed in Sections 3 and 4 – are analyzed within
the context of a system that maintains itself (and consequently maintains the
components involved in generating the phenomenon) and characterized in
terms of the contribution to the maintenance of the system. A further difference
with new mechanism is that by treating the biological system as a whole as the
starting point and the main explanatory target, the organizational framework
gives priority to identifying what functions are necessary to produce and
maintain it and how they depend on one another, not to describing how
a specific biological phenomenon is materially realized. These functional rela-
tions establish the requirements for the components and allow that any compo-
nent that meets them will suffice. This does not mean denying the role of
materiality, as seen in Section 3, but just that the materiality of the individual
components is the distinguishing feature of the system.
Due to the differences in the focus and in the role ascribed to the material
properties of components, new mechanists and organizational theorists engage in
decomposition in different ways. While organizational theorists have mostly
addressed general theoretical questions, the new mechanists have focused on
the research strategies employed by scientists to develop explanations: localizing
the phenomenon in a mechanism, decomposing it into constituent parts, deter-
mining what activities or operations these parts perform, and then determining
how the parts are organized to generate the phenomenon. These activities take the
mechanism as the relevant unit. Decomposition implies identifying the material
components involved in the production of a phenomenon. This, however, is only
the first step in developing a mechanistic explanation: Researchers must also
recompose it and resituate it in the context in which it operates to establish that the
operations of the parts together suffice for producing the phenomenon (Bechtel,
2009). By doing so, research on mechanisms proceeds both top-down from the
phenomenon to the constitution of the mechanism and bottom-up to reconstruct
the phenomenon for which the mechanism is responsible.
Work on biological organization has not engaged in decomposition in the
same way as described by the mechanists. This tradition has privileged
approaches that take the whole system as the relevant unit. When they refer to
parts of living system, organizational theorists do so functionally in terms of
their contribution to the organization of system that they together realize, rather
than in terms of material properties. Some advocates of this tradition, such as
Rosen (1991), have argued that bottom-up and top-down descriptions may not
be just one the inverse of the other, and their results might not coincide.
Therefore, starting from the material parts might lead to missing something of
the functioning of the whole system. As a consequence, this tradition, especially
the early work, has been characterized by a high degree of generality and
abstraction from materiality.
Bich and Bechtel (2021, 2022b) have argued that despite the differences and
the important insights produced by each separately, the mechanistic and organ-
izational approaches are not mutually exclusive. The common focus on organ-
ization makes them complementary, and each can benefit from engagement with
the other. While mechanistic approaches can benefit from situating mechanisms
in the context of a self-maintaining organization, adopting mechanistic
approaches may help to develop organizational theories and explanations by
grounding them in an understanding of how different phenomena are actually
realized by biological systems.
Three main points of contact favor this mutual engagement. The first point
consists of the adoption of a common framework based on constraints. In
Section 3, we have seen how constraints figure in the work of organizational
theorists as they develop the ideas of closure of constraints and regulatory

control. The recent reframing of new mechanism by Winning and Bechtel
(2018) is also grounded in the notion of constraint.30 They consider the compo-
nents of mechanisms as imposing constraints restricting the flow of free energy.
In their view, biological mechanisms are active because they constrain free
energy so as to perform work. Therefore, mechanisms should not be understood
simply as organized sets of entities and activities. They are characterized as
organized sets of constraints that direct the flow of available free energy so as to
carry out the work that generates the phenomenon for which the mechanism is
taken to be responsible (see also Militello & Moreno, 2018). Constraints
constitute a common ground shared by these two frameworks. Reframing
mechanisms in terms of constraints provides the conceptual tools to understand
them in a system realizing closure of constraints.
The second point is the notion of organizational functions. Mechanists often
speak of mechanisms and their parts as performing functions, but the accounts
of function traditionally on offer are not sufficiently focused to characterize
functions of biological mechanisms (see Section 5.2). Drawing upon the refor-
mulation of mechanisms in terms of constraints, one can adopt the organiza-
tional account and characterize the functions of mechanisms in terms of their
contributions to the maintenance of specific biological systems. This allows one
to explain the existence and operation of a mechanism by referring to its
function within the system.31
The third point of contact is the focus on control. The reframed account of
mechanism developed by Winning and Bechtel (2018) distinguishes between
two types of mechanisms: production and control mechanisms. Production
mechanisms are those responsible for generating a phenomenon. They perform
physiological and behavioral activities such as synthesis of components, gener-
ation of movement, and so on. Control mechanisms instead – similarly to
control constraints in the organizational framework – are responsible for chan-
ging the behavior of other mechanisms. They do so by modifying some of the
constraints active in production mechanisms, and they do so on the basis of the
measurement of some variables. Most of the mechanisms characterized by the
30
Piekarski (2023) calls it “the constraint-based mechanisms approach.”
31
Other advocates of new mechanism engage in functional analysis in a different way. They do not
ascribe functions by referring to the maintenance of the system, but mostly based on a causal role
account of functions. In this case, functional analysis is considered as a mechanism “sketch,” that
helps in the identification of mechanisms (Piccinini & Craver, 2011). It consists of the analysis of
a phenomenon or a capacity in terms of the functional properties of a system. It then requires
identifying the structures that possess those functional properties and to fit them into mechan-
isms. However, once functions are associated with the subjacent mechanisms that realize them,
the functional description is replaced by the mechanistic one.
new mechanists can be characterized as production mechanisms – they con-

strain free energy to carry out a productive activity – constructing or degrading
something, moving things, and so on. The second type of mechanisms, control
mechanisms, also operates as a result of constraining flows of free energy, but
they do so to modify constraints in other mechanisms, thereby determining how
those mechanisms operate. They direct the activities of production mechanisms.
However, in biological systems, control does not just consist in modifying
production mechanisms. As seen in Section 4, biological control is performed
in such a way as to maintain the organism: It is functional and regulatory.
Looking at control mechanisms in context of a self-maintaining system subject
to closure is useful to understand why there are control mechanisms in the first
place, to flesh out their functional dimension, and understand why production
mechanisms need them in order to operate as parts of the system (Bich &
Bechtel, 2022a, 2022b). By adopting this perspective, a living system is under-
stood as consisting of the set of mechanisms responsible for generating the
phenomena that are needed so that the system is maintained and for doing so
when they needed. Control is paramount for this. Control mechanisms perform
the measurements of variables that determine whether the activity of
a mechanism is needed or not, and then activate or inhibit it accordingly. This
important dimension of biological systems would be simply lost if new mech-
anists treated living systems as simply collections of mechanisms.
Drawing upon these conceptual bridges between the two frameworks, new
mechanists can employ insights of the organizational tradition in addressing
crucial questions about how to select phenomena, identify components of
mechanisms, and generalize mechanistic accounts (Bich & Bechtel, 2021).
Let us start with the characterization of phenomena to be explained in terms
of mechanisms. A vast number of regularities or repeatable events occur within
living systems, yet only some of them are picked out to be explained. What is
needed is an account of what to count as a relevant phenomenon and how to
identify it. The organizational account of functions may provide criteria from
which to select which among the activities occurring in a living system are
phenomena to be explained. From an organizational perspective, it would be
important to explain those activities that count as functions in virtue of their
contribution to the maintenance of the current living system.
Let us then consider the issue of the identification of the components of
mechanisms. Once a phenomenon has been selected, one needs criteria to deter-
mine which entities constitute the mechanism responsible for the phenomenon, and
which do not. Considering as components all those entities that have an effect on
the phenomenon would include too many. To establish the boundaries of mechan-
isms one needs to unbundle a vast network of causally interacting entities to select
the relevant ones, with interactions extending also out into the environment. One
way to do so is to distinguish control interactions from those taking place within
controlled mechanisms. This can be done by focusing on what a mechanism is
doing. Considering whether a mechanism operates on other mechanisms (control)
provides a principled way of drawing the boundaries of production and control
mechanisms. In the specific case of control mechanisms, a further way to establish
boundaries is to consider that they perform measurements. Entities whose features
are being measured have an effect on the mechanism, but they are not parts of it.
Moving to generalizations, a further challenge confronting new mechanists
derives from the fact that research on mechanisms is usually focused on specific
instances of a mechanism, often realized in a specific system. Mechanistic
explanations, however, rely on regularities and aim to extrapolate from specific
cases, and abstract from details, to provide generalizations. One way to do so is to
identify phylogenetic relations between instances of a mechanism in different
systems. However, differences between mechanisms (or between the organisms
harboring them) that have emerged during a history of adaptations might make it
unclear whether or not it is possible to extrapolate and generalize. The organiza-
tional framework offers a possible solution by considering whether different
instances of a mechanism in different systems serve the maintenance of the
organism in the same way. If they do not, the differences may not allow general-
izations. If the instances of the mechanism contribute to the maintenance of the
organism in the same manner, the extrapolation from one system to the other is
justified. The same holds for abstractions. If abstracting from the specific details
of a mechanism still allows researchers to explain how it performs its function in
the system, then the result can be in principle used to develop generalizations.
From the point of view of the organizational framework, one of the main
advantages of engaging with new mechanism consists in the possibility to
overcome the high degree of abstraction and develop better biological explan-
ations grounded in materiality. Organizational theorists can ground their
accounts in an understanding of the mechanisms employed in achieving and
maintaining closure. This does not imply abandoning the top-down strategy
that starts with the identification of functions and then of the components that
realize them. Components can still be characterized primarily in terms of how
they contribute to the maintenance of the system, instead of their structural
features. However, engaging with new mechanism provides further tools to
proceed down to material processes and constraints to explain how they are
produced and maintained and what role they play within the system.
Employing the revised notion of mechanism as organized sets of constraints
may also contribute to providing better and more precise biological explanations
and functional attributions. According to the organizational framework, the
entities responsible for those biological activities that would coincide with
biological functions are individual constraints (Mossio et al., 2009). More pre-
cisely, each functional activity is performed by a constraint, and closure consists
in the mutual dependence between these functional constraints. As argued by
Bich and Bechtel (2021), identifying a constraint with a biological function may
be an abstraction. While useful in some cases for explanatory purposes, nonethe-
less it risks overlooking the complexity underlying the realization of biological
functions and how this complexity matters for the overall functioning of the
system. This can be seen already in the relatively simple case of an enzyme,
which is often used as a paradigmatic example of functional constraint. The
different parts of the enzyme, such as the catalytic site, the phosphorylation and
allosteric sites, structures that undergo conformational changes, and so on,
contribute differently to the function performed by the enzyme. This function
might be better characterized in terms of a mechanism employing several inter-
acting constraints rather than one monolithic constraint. This is even more
relevant in multicellular organisms, where the activity of organs depends on the
interaction of different structures or cell types constituting them. Let us think of
the muscles, valves, and so on, that constitute the heart, or alpha and beta cells,
among others, in the pancreas. Signaling control pathways are another example.
They are present in all living systems and play different functional roles as a result
of being differently regulated in different parts of the system on the basis of the
state of the system or the environment. Pathways are usually characterized by
several steps in which the various parts involved sense variations and act in turn
on other parts accordingly. They often branch and affect distinct parts or establish
crosstalk with other pathways. Let us think, for example, of all the steps involved
in the release of insulin and the control of glucose metabolism in glycemia
regulation: from sensing the energetic state of the system by pancreatic beta
cells and the activation of the molecular machinery for the release of insulin into
the blood, to the action of insulin in the metabolism of the receiving cells. Each
step in this pathway can be also subject to control exerted by constraints from
other pathways. This phenomenon might be better understood in terms of sets of
constraints organized into mechanisms, rather than as one constraint (insulin or
beta cells) acting upon glucose metabolism.
8 Open Challenges: Symbiotic Associations

and the Environment
In the previous sections, we have seen how several objections have been advanced
to different aspects of the organizational framework, both from without and within
the community working on it. Some put into question the possibility of univocally
operationalizing constraints (Cusimano & Steiner, 2020) and the capability to

ground cross-generation functions (Artiga & Martinez, 2016). Others criticize
functional attributions in terms of self-maintenance as too liberal (Garson,
2017), or the very notion of closure as too abstract to provide detailed biological
explanations and account for the complexity of biological systems (Bich &
Bechtel, 2021, 2022b), and so on. Some of these criticisms have been addressed
by organizational theorists, others not yet. In this section, I will conclude by
discussing two challenges to the application of an organizational framework in
biology, which derive from its distinctive inward-looking perspective focused on
the internal organization of biological systems and on the notion of self-
maintenance: symbiotic associations and the characterization of the environment.
Both have to do with how to understand living systems in a wider context. These
challenges have not been extensively addressed by organizational theorists, but
I will sketch some possible ways to face them based on existing literature.
8.1 Symbiosis
The first challenge is presented by the debate on biological individuality in the
light of new studies on highly integrated collective or composite entities arising
out of interactions, from biofilms to holobionts (multicellular hosts with all their
associated microbes), from colonies to social insects. Historically, the organ-
izational framework has been developed and applied in biology usually by
having in mind organisms as the main target, and by relying on the identification
of physical boundaries (such as membranes) and on the use of notions such as
closure in order to identify and characterize living systems. However, recent
research on complex and highly heterogeneous biological associations such as
host-microbiota and, more generally, symbiotic relationships characterized by
close functional ties, seems to put into questions the possibility of establishing
clear (functional) boundaries for biological systems (Bosch & McFall-Nagai,
2011; Gilbert et al., 2012; Skillings, 2016). Or at least it calls for further work on
characterization of the different ways functional interactions can be established
within a system or between systems.
Although at first sight these cases might be seen as problematic for the
organizational framework, it is not necessarily the case. It is important first to
clarify that organizational closure does not imply independence or self-sufficiency.
In principle, closure is not incompatible with forms of dependence, and a system
can be self-maintaining in the sense that it realizes closure even though it is not
independent from other systems or its environment. However, very tight depend-
encies such as those implied by some symbiotic associations may require specific
discussion. Although more work is needed, a possible response to this challenge
can be found in the very characterization of an integrated system provided by the

organizational framework. In this view, subsystems contribute to one another’s
conditions of existence by mutually controlling their functional processes in such
a way as to achieve closure (Bich, 2024b). This very general idea allows one not
only to understand living systems such as organisms as cohesive entities (i.e.
individuals), but also to account for those interactions between different biological
systems that are necessary for the maintenance of the systems involved, without
the need to put into question core notions such as closure (Bich, 2019). Let us see it
in more detail.
Regulated closure of constraints is characterized as a causal regime of mutually
dependent constraints that determines and modulates a subset of its own conditions
of existence, not all of them. One implication is that identifying a system satisfying
these conditions does not require identifying all the possible interactions, but just
a set of mutually dependent constraints that realize a form of self-maintenance:
a minimal loop between constraints. Another implication is that once mutual
dependence between constraints is realized within a system, thus achieving closure,
this self-maintaining system can have functional interactions with other biological
systems. As argued in Bich (2019), among those interactions some can take the
form of a mutual dependence between (basic or control) constraints built by the two
systems. Given two biological systems A and B realizing closure, system
A constrains processes in system B while B also constrains processes in A. By
doing so, they are achieving some form of integration across systems, and possibly
realizing a new super-organismal organization.32 If this new organization satisfies
the requirements for closure of constraints, it constitutes a new (higher-level)
regime of closure (Montévil & Mossio, 2015).
It is worth emphasizing that doing so does not imply per se that once they
establish these interactions, the organisms involved are not able to realize
organizational closure by themselves anymore. It means, instead, that while
maintaining closure as functionally cohesive entities, biological systems can
extend their functional networks of constraints by realizing nested integrated
causal regimes that include more than one system.33
32
This scenario is different from the phenomenon of biological communication discussed in
Section 6. The organizational account of communication as influence does not imply the degree
of integration required by higher levels of closure, according to which systems or subsystems
directly control one another’s physiological processes by exchanging constraints. Each partner in
a communicative interaction controls its own physiological processes. What happens in the case
of communication is that a signal emitted by one of the partners is sensed by the other and
triggers a behavioral reaction in the receiver which is functional for the sender. The two
communicating partners are not building a larger system subject to closure.
33
Montévil and Mossio (2015) use the expression “higher level closure” for cases of nested closure
such as cells in a multicellular system and use the expression “tendency to closure” to refer to the
degree of functional dependence between systems.
How this is done and what are its implications needs to be evaluated case by
case depending on the types of interactions between the systems involved (see
e.g. Bich, 2019 and Skillings, 2019). Let us consider two examples to illustrate
different scenarios in which such an evaluation could be carried out. Eukaryotic
organelles of endosymbiotic origin such as mitochondria and chloroplasts, for
example, might be considered as cases resulting from an evolutionary process in
which one of the partners lost the capability to realize closure of constraints
while the other, the host cells, kept it and incorporated the symbionts as organelles
into its own regime of closure. In this case, interactions between two systems gave
rise to one system realizing closure. Current cases of intracellular endosymbiosis
are instead possible candidates to be evaluated as systems realizing higher-level
closure of constraints if a mutual dependence in terms of constraints can be
identified, as each partner engages in functional interactions without stopping to
realize an internal regime of closure.
8.2 Biological Organization and the Environment

Let us move now to the second challenge: the characterization of the environment.
One possible worry about the organizational framework is that it may be too
focused on the living system, and only considers the environment through the
notion of thermodynamic openness, as a necessary yet generic source of matter and
energy, or as a source of noise and perturbations to be counteracted. However, the
organizational framework can deploy two possible strategies to consider and better
characterize the environment: an adaptivity strategy and an ecosystems strategy.
The first strategy, pursued by Menatti and collaborators (Menatti et al., 2022),
is inspired by the notion of adaptivity introduced by Di Paolo (2005) and
developed in the organizational account of regulatory control (Bich et al.,
2016). Adaptivity is defined by Di Paolo as the capability of a system, such as
an organism, to remain viable in its environment by regulating itself. It desig-
nates the ability of a system to cope with changes in the environment. As
discussed in Section 4, this idea has been developed into an account of regula-
tory control of the activity of those constraints responsible for generating the
internal dynamics and behavior of a system, by modulating them in relation to
variations in internal and external conditions. Such modulation is carried out by
means of specialized constraints or mechanisms that evaluate perturbations and
operate accordingly.
To provide a characterization of the environment, Menatti et al. (2022) focus
on the fact that regulatory adaptivity enables the organism to actively engage
with the environment by promoting change.34 According to this approach, the
34
The main target of this work is the relationship between environment and health.
environment is characterized relationally, in terms of the type of evaluation

operated by living systems under variable conditions and the actions they take.
A biological system needs to manage interactions with the environment in such
a way as to maintain itself viable. It does so through regulatory control by
making decisions based on what it senses in its surroundings. From this
perspective, the environment of a system ceases to be a set of independent
boundary conditions or a generic source of noise. It is seen as a source of
different types of opportunities that allow a system to modify itself to maintain
or expand its range of viability. This can be achieved by modifying the system
itself, or by acting in and modulating the surroundings to promote their condi-
tions of existence so as to create more supportive ones.
In this view, an environment can be categorized by a system according to
how interactions unfold and what types of changes a system can carry out
during them. Some interactions with the environment might require specific
operations aimed at counteracting or compensating for the effects of the
interaction. Most of them would require the system to change its current
regime in specific ways to take advantage of them. Let us think, for example,
of the light and dark cycle, and the importance it holds in different ways by
enabling different activities for photosynthetic organisms or nocturnal ani-
mals. For some other systems this very cycle might not be relevant, as it would
not trigger regulatory activities. By accounting for these differences, this
approach aims to provide a fine-grained characterization of the environment
of a living system or group of systems by focusing on the interface between
a system’s regulatory capabilities and the properties and dynamics taking
place in its surroundings.
The second strategy – the ecosystems strategy pursued by El-Hani and
collaborators (Nunes-Neto et al., 2014; El-Hani & Nunes-Neto, 2020; El-
Hani et al., submitted) – also employs the conceptual tools of the organiza-
tional frameworks. But it zooms out from the relationship between the inner
operations of living systems and properties of the surroundings to focus on
larger networks of interacting entities that include living systems and abiotic
elements, collectively operating on fluxes of matter and energy. It looks at
interactions within the environment of living systems: at how an ecosystem is
organized and can be identified, and at how to evaluate if entities can be
included in it or not.
The basis for doing this is constituted by the organizational account of
ecological functions (Nunes-Neto et al., 2014). This account proposes the thesis
that ecological interactions between organisms can realize a form of collective
closure between organisms, whose self-maintaining regime goes beyond the
individual organisms. This interspecies collective regime of organizational
closure is realized by means of mutual constraints exerted by groups of organ-

isms on one another’s external boundary conditions. It is different from the
regime of closure realized within living organisms because in principle it does
not involve regulatory control modulating the operation of its parts. It involves
only basic constraints exerted by different ecological communities on the envir-
onmental flux of matter and energy crossing the larger system. On this account,
if an ecological system can be shown to realize a regime of closure, then this
regime can be used to ground functional attributions in terms of contribution
of the participants to the more comprehensive ecological organization (Nunes-
Neto et al., 2014).
The example employed to illustrate this possibility is the interaction between
bromeliad plants and their associated organisms such as spiders that live and hunt on
it, larvae and adults of mosquitos, and microorganisms (Figure 8). The plant exerts
constraints on the external conditions of the animals. It provides spiders with the
structural support for building their webs, and it realizes structures that allow the
accumulation of water (phytotelmata) where larvae of mosquitos and microorgan-
isms can thrive. The spiders in turn constrain the conditions of existence of the plant:
They canalize the flux of nitrogen by hunting mosquitos. Nitrogen, proteins, and
amino acids contained in the spiders’ carcasses and feces, as well as in the preys’
carcasses that fall into the phylotemata, are processed by microorganisms and
absorbed by the plant and by the mosquitos, which in turn are eaten by the spiders.
If these relations can be characterized in terms of closure, then according to this
account each of these entities can be said to be exerting a function.35
This account provides a perspective from which to look at the organization of
the environment. By doing so, it allows organizational theorists to make fine-
grained distinctions in an otherwise generic medium. It also grounds distinc-
tions between environmental constraints that are part of a given ecological
organization or external to it. In this view, to be included in the system, an
entity should be a constraint that is both dependent on other constraints in the
system and enabling the activity of other constraints in it (El-Hani et al.,
submitted). Such constraints can be directly exerted by living organisms but
also by abiotic entities (El-Hani & Nunes-Neto, 2020). In this view an abiotic
35
Lean (2021) criticizes this approach by arguing that it might be impossible to identify cases of
closure in ecological systems, apart from very special cases such as this, usually restricted to the
interaction of two or few more species in a very narrow and spatially contiguous niche. El-Hani
et al. (2023) respond to this criticism by arguing that difficulties stem from the fact that
organizationally closed systems show different degrees of cohesion, and ecological systems
are situated among the less integrated ones. Therefore, one cannot expect the same degree of
cohesiveness found within living organisms. In order to identify an ecological system as
organizational closed, it is sufficient to include just part of the constraints exerting influence
over the system, but sufficient to give rise to a causal loop. It does not require to extend the scope
of the analysis to include all possible constraints involved.
Figure 8 A bromeliad plant and its associated organisms (from Nunes-Neto

et al., 2014, reproduced with permission from Springer Nature).
item such as fire interacting with vegetation can be a functional component of an

ecosystem’s organization if it is subject to closure within that system, that is, if it
is both a dependent (i.e. subject to constraints internal to the system) and
enabling constraint (i.e. affecting its dynamic and contributing to the mainten-
ance of the system). An item (biotic or abiotic) is external to the system, instead,
if it is only a boundary condition not directly dependent on the system.
The adaptivity and ecosystems approaches to the environment are linked
because both depend on a living system’s capabilities to exert control on its
external conditions of existence. One builds upon the internal regulated closure
of constraint of living systems and how it allows establishing different types of
interactions with the surroundings, thus letting its different features emerge
from a background noise. The other identifies a basic regime of closure realized
between living systems. The distinctive feature of the ecological strategy is its
focus on what systems do that constrains the external conditions of existence of
other living systems, either by directly harnessing the external flux of matter and
energy, or indirectly by generating external constrains in the environment (e.g.
bird nests, spider webs, beaver dams, etc.).
In this final section, I discussed just two of the possible challenges faced by
the organizational framework. More challenges and criticisms are going to
appear that need to be addressed. After all, this is still a recent approach in the
philosophy of biology, pursued by a relatively small, although growing, com-
munity of researchers. The development of the organizational framework is an
ongoing endeavor, undergoing reframing such as the formulation of closure in
terms of constraints and the incorporation of regulatory control. This process is

accompanied by the revision of core notions such as function and teleology or
closure itself. There is still more work to do to improve an understanding of
living systems from an organizational perspective, to provide explanations of
biological phenomena, and to further develop and revise the framework to
better account for the complexity of living systems.
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Acknowledgments
I thank Laura Menatti for her love and support, for our discussions and
collaborations, and for so many other things that listing them would easily
exceed the space of an Element. The idea of writing this Element came out in
a conversation with Derek Skillings, who was trying to keep me awake while
I was driving during a long car trip in the south of France. I am grateful to him
for encouraging me, for discussing many ideas in philosophy of biology, and for
supporting me with his friendship. A substantial part of this Element was
written during my guest fellowship at the KLI – Konrad Lorenz Institute for
Evolution and Cognition Research (from Fall 2022 to Spring 2023). I thank the
director Guido Caniglia, and all its members and fellows for the kind hospitality
and for providing a very serene and stimulating research environment. I wish to
thank William Bechtel for the many helpful suggestions and, together with
Andrew Bollhagen and Matteo Mossio, for the very helpful feedback on
a previous version of the manuscript. I thank Alvaro Moreno and all my other
co-authors for the very stimulating conversations and the collaborative work,
which over the years have contributed to shaping my way of thinking about
living systems.
Funding
This research was supported by grant Ramón y Cajal RYC-2016–19798 funded
by MCIN/AEI /10.13039/501100011033 and by ESF “Investing in your
future”; by grant PID2019-104576GB-I00 for project Outonomy funded by
MCIN/AEI/10.13039/501100011033; and by grant IT1668-22 funded by the
Basque Government. The open access publication of this book was funded by
the John Templeton Foundation (grant #62220). I deeply thank Alvaro Moreno
and Derek Skillings for making these funds available from their subawards. The
viewpoints expressed in this Element are those of the author and not those of the
John Templeton Foundation.
Conflict of Interest
The author has no conflict of interest to declare.
Philosophy of Biology
Grant Ramsey
KU Leuven
Grant Ramsey is a BOFZAP research professor at the Institute of Philosophy,
KU Leuven, Belgium. His work centers on philosophical problems at the foundation of
evolutionary biology. He has been awarded the Popper Prize twice for his work in this area.
He also publishes in the philosophy of animal behavior, human nature and the moral
emotions. He runs the Ramsey Lab (theramseylab.org), a highly collaborative research
group focused on issues in the philosophy of the life sciences.
Michael Ruse
Florida State University
Michael Ruse is the Lucyle T. Werkmeister Professor of Philosophy and the Director
of the Program in the History and Philosophy of Science at Florida State University.
He is Professor Emeritus at the University of Guelph, in Ontario, Canada. He is a former
Guggenheim fellow and Gifford lecturer. He is the author or editor of over sixty books,
most recently Darwinism as Religion: What Literature Tells Us about Evolution; On Purpose;
The Problem of War: Darwinism, Christianity, and their Battle to Understand Human
Conflict; and A Meaning to Life.
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Elements in the Philosophy of Biology

Abstract: Living systems are complex systems made of components

Keywords: organization, autonomy, control, mechanism, organisms

© Leonardo Bich 2024

1 Introduction: Understanding What Makes a System Living 1

2 Diﬀerent Uses of Organization: Organizational Motifs,

3 Biological Organization as a Self-Maintaining Causal

4 Reinterpreting Closure: From Basic Self-Maintenance

5 Naturalizing Biological Teleology and Functions 32

6 Interpreting Biological Phenomena through the Lens

7 Bridging Philosophical Frameworks: Organization

8 Open Challenges: Symbiotic Associations and the

1 Introduction: Understanding What Makes a System Living

bacterial receptors activates the expression of several genes, including those

2 Diﬀerent Uses of Organization: Organizational Motifs,

The way organization has been addressed in biology by the theoretical

Figure 1 A basic example of negative feedback loop from molecular biology:

system. A pathway so organized with a negative feedback mechanism realizes

the nonlinear interactions between components. Developed in close parallel

modeling tools to understand their behaviors. Examples of this are protein

3 Biological Organization as a Self-Maintaining Causal Regime:

is characterized, details can be ﬁlled in and it can be used to shed light on

Departing from the traditional characterization of organizational closure and

(1) at a time-scale characteristic of P, C is locally unaffected by P;

Figure 2 An abstract representation of closure of constraints (Montévil &

production and maintenance, and collectively contribute to the maintenance of the

Figure 3 General representation of glucose uptake, distribution, and

the phenomenon of glucose uptake and transformation through the digestive

constrained by glucose transporters in the cell membrane; (4) intracellular glycoly-

4 Reinterpreting Closure: From Basic Self-Maintenance

With regards to biological grounding, the notion of closure of constraints

regime of closure would simply “absorb” as a network the effects of a limited

depending on internal and external conditions. Within the organizational frame-

Within the organizational framework, regulatory control entails an architec-

Figure 4 General relational diagram of regulatory control as the activity

Regulatory control, as employed in this case, is what allows biological systems

they need to coordinate these capacities by regulating their activities so that

Figure 5 Representation of the regulation of glucose metabolism in mammals

5 Naturalizing Biological Teleology and Functions

5.1 Organization and Teleology

The organizational framework focuses on current systems as the grounds for

Evolutionary accounts focus on functions and traits. They look outside

in so doing they contribute to the maintenance of the system. Developing

organizational account of teleology by treating a living organism not only as

5.2 Organization and Functions

(1) The organization of the system S to which T belongs realizes closure of

In a system that realizes a self-determining teleological organization, where the

survival of an organism might not have been previously selected as adaptations.

considerations, because it provides a different grounding for functional attribu-

6 Interpreting Biological Phenomena through the Lens

6.1 Origins of Life

totally rely on knowledge of present-day biological systems to infer the features

6.2 Biological Communication

may include attempts by synthetic biologists to design artiﬁcial protocells

of the current organization of the system rather than in terms of evolutionary

Figure 7 Communication between biological systems A and B. The dotted line

7 Bridging Philosophical Frameworks: Organization

explanations of biological phenomena. The reason is attributed to the fact that

account of mechanism, organization plays a more decisive role. In their

theorists as they develop the ideas of closure of constraints and regulatory

new mechanists can be characterized as production mechanisms – they con-

8 Open Challenges: Symbiotic Associations

operationalizing constraints (Cusimano & Steiner, 2020) and the capability to

can be found in the very characterization of an integrated system provided by the

8.2 Biological Organization and the Environment

environment is characterized relationally, in terms of the type of evaluation

closure is realized by means of mutual constraints exerted by groups of organ-

Figure 8 A bromeliad plant and its associated organisms (from Nunes-Neto

item such as ﬁre interacting with vegetation can be a functional component of an