biological landscape. The first is the theory
of evolution put forth by Charles Darwin
150 years ago (Darwin 1859). Recently, Mi-
chael Willig and I presented a similar
broad-level theory for ecology (Scheiner
and Willig 2008). The purpose of this pa-
per is to lay out a series of theories that
encompass all of biology: an overarching
theory and five general theories. In doing
so, I will take Dobzhansky’s (1964) apho-
rism that nothing in biology makes sense
except in the light of evolution and dem-
onstrate that the complement is also true.
Evolution is just one of several general do-
mains within biology. All of those domains
intersect and interact, and none holds pre-
cedence (Griesemer 2006). The theory of
evolution has been given precedence be-
cause, until recently, it was the only do-
main with a well-articulated theory.
The purpose of this paper is to provide
well-articulated theories for the rest of biol-
ogy. I shall accomplish this task by first
briefly reviewing the theory of evolution as
an example of the nature and structure of
theories in biology. With that as an exem-
plar, I will present a hierarchical structure
for theories. I will then outline the overarch-
ing theory and the other four general theo-
ries. Next, I will discuss how you, the reader,
can use this knowledge to frame your own
research and make it bolder and riskier. Fi-
nally, I will point out aspects of biological
theories that only become apparent once they
are made explicit, discuss how such theories
can change the way that we teach biology, and
examine possible next steps in theory develop-
ment within biology.
This presentation may seem abstract and
distant from your day-to-day activities as a
scientist, but, as you read this essay, con-
sider how you might use the information
revealed. Toward the end, I will discuss
some of the immediate, practical uses of
this conceptual framework.
The Theory of Evolution as
Exemplar
the general theory
The theory of evolution should be famil-
iar to all biologists (Table 1). Its funda-
mental principles were articulated in Dar-
win’s On the Origin of Species, were further
refined during the Modern Synthesis, and
are still in the process of being debated
(e.g., Mayr and Provine 1980; Bowler 1983;
Smocovitis 1996; Kutschera and Niklas
2004). The theory of evolution can be en-
capsulated as seven fundamental princi-
ples. (My starting point for the distillation
of the theory of evolution was Kutschera
and Niklas [2004], with various reorder-
ings and renumberings. Not discussed in
their paper is the role of contingency [Ta-
ble 1, principle 7]. I recognize that others
might disagree with the exact number and
wording of these principles, but such dis-
agreements over details do not alter the
general form of my thesis.) The theory de-
fines a domain: intergenerational patterns
of change and stasis of the characteristics
of organisms, including causes and conse-
quences. This domain encompasses micro-
evolution, macroevolution, and the origin
of species, as well as evolution’s tempos
and modes.
This formulation of a theory as a set of
statements consisting of concepts and con-
firmed generalization is in line with how
many philosophers view theories (van
Fraassen 1980; Giere 1988; Beatty 1997;
Longino 2002; Pickett et al. 2007; Wimsatt
2007; del Rio 2008; NRC 2008), and is sim-
TABLE 1
The domain and fundamental principles of the
theory of evolution
Domain
The intergenerational patterns of the characteristics of
organisms, including causes and consequences
Principles
1. The characteristics of organisms change over
generations.
2. Species give rise to other species.
3. All organisms are linked through common descent.
4. Evolution occurs through gradual processes.
5. Variation among organisms within species in their
genotype and phenotype is necessary for evolutionary
change.
6. Evolutionary change is caused primarily by natural
selection.
7. Evolution depends on contingencies.
294 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

ilar to the presentation by Darwin. All of
the fundamental principles can be found
in some form in On the Origin of Species,
although their meaning and our under-
standing of them has greatly changed in
150 years. It is a testimony to Darwin’s ge-
nius that he thought so deeply and broadly
about the theory that he was setting forth.
However, it in no way denigrates that ge-
nius to point out the many things that he
got wrong, did not understand, or did not
know about (e.g., genetics).
The first three principles—descent with
modification, speciation, and single ori-
gin—are about the facts of evolution per se.
By the 1860s, they were widely accepted by
the community of scientists focused on
these issues (Ruse 1999), and they have not
been seriously questioned within the scien-
tific community since (Bowler 1983, 2004).
The other four fundamental principles—
gradualism, variation, natural selection, and
contingency—are a different story. These
principles are about the mechanisms of
evolution. They have been, and continue
to be, the subject of sometimes vociferous
debate. Despite today’s general percep-
tion, natural selection was not accepted as
the primary mechanism of evolution in the
late nineteenth and early twentieth centu-
ries (Bowler 1983; Ruse 1999). It was not
until the Modern Synthesis that we saw a
clear ascendancy of natural selection as the
primary mechanism (Smocovitis 1996).
The process of the Modern Synthesis can
be seen as a pruning away of some mech-
anisms (e.g., goal directed processes), the
refining of others (e.g., genetics), and ar-
guing over the relative importance of yet
others (e.g., mutation vs. drift vs. natural
selection).
The past 50 years have seen additional
debates over those mechanisms and the
meaning of the concepts embodied in the
fundamental principles. Those debates
have been many; I touch on just a few here
to illustrate the process of theory change.
Gradualism (Table 1, principle 4) in the
nineteenth century clearly referred to a
very slow process—“Natura non facit sal-
tum [nature does not make a leap]” (Dar-
win 1859:471). We now recognize that
natural selection can result in substantial
change in tens of generations. However,
the mean of a trait value or an allelic fre-
quency in a population changes little with
each generation and, more importantly, is
continuous relative to the total variation
within that population. Today’s under-
standing of this principle follows Simpson
(1944), who acknowledged that the tempo
of evolution can be quite variable. This
understanding can be contrasted with the
various forms of saltationism that have
been proposed over the decades, all of
which posit a large change in a single gen-
eration, where “large” generally means out-
side the range of standing variation. One
recent example is the theory of punctuated
equilibrium, which, in its original version
(Eldredge and Gould 1972), claimed that
all evolutionary change occurred in a sin-
gle generation associated with the process
of speciation, although this extreme position
was later softened (Gould and Eldredge
1977, 1993).
Recent debates about the origin of pheno-
typic novelties (e.g., West-Eberhard 2003), as
well as the emerging discipline of evo-devo
(Gilbert and Epel 2009), have focused on
the meaning of and the mechanisms un-
derlying fundamental principle 5 (Table
1). The neutralist versus selectionist de-
bates of the 1960s to 1980s were about the
relative importance of the mechanisms em-
bodied in fundamental principles 6 and 7.
Of course, this is an oversimplification, and
often the debates were about several prin-
ciples simultaneously; however, it clarifies
those debates to link specific parts to par-
ticular fundamental principles.
One debate demonstrates a definitional
resolution. The relative importance of natu-
ral and sexual selection was argued in the
1980s (summarized in Michod and Levin
1988) and was, in effect, a debate over
whether there should be an additional fun-
damental principle about sexual selection
and a change in fundamental principle 5.
The debate was resolved by defining natural
selection so that it encompassed all possible
forms of selection (Endler 1986). This result
subsumed the debate over the relative im-
portance of different mechanisms of selec-
September 2010 295TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

tion within fundamental principle 5, so that
the debate was no longer about the principle
itself, but about subsidiary theories instead.
As described in Table 1, the theory of
evolution provides several clues about the
structure of theory. All of the fundamental
principles are broad generalizations about
evolutionary patterns and processes, and
whole subdisciplines are contained within
a single principle. The principles are not
directly predictive statements, at least not
in a quantitative sense. That is the role of
subsidiary theories and models.
subsidiary theories and models
Within the general theory of evolution
are nested a large variety of more specific
theories. As an exemplar, consider the the-
ory of natural selection. That theory con-
sists of the following syllogism (Darwin
1859; Endler 1986):
If individuals within a population vary
in their characteristics, and
if that phenotypic variation causes differ-
ences in reproductive success, and
if that phenotypic variation is heritable,
then the population will change its charac-
teristics over generations.
Like the more general theory, this theory
also generates many specific subtheories that
are often labeled “models” when they have a
mathematical formulation. For example,
one instantiation of the theory is the familiar
breeder’s equation:
z

sVG/VP, in which
the change in the mean phenotype of a trait
(
z
) is a function of the strength of selection
(s), the genetic variance of that trait (VG),
and the phenotypic variance (VP). (Typically
the ratio of genetic to phenotypic variance is
shown as the heritability, h2). This is a quan-
titative genetics model in which each of the
four terms corresponds to one of the four
components of the syllogism. One function
of subtheories is to provide guidelines for
model construction.
A completely different instantiation
is a genic, single-locus model:
p 
sp1 p2
1 s1 p2
, in which the change in the
frequency of an allele (p) is a function of
the strength of selection and the current
allele frequency. Both equations are valid,
both contain a long list of overlapping but
different background assumptions, and
they can both be linked if additional assump-
tions are made (Price 1970; Lynch and
Walsh 1998).
Theory, in General
the structure and role of theory
Now that we have looked at one general
theory, let us consider theory and its struc-
ture (Tables 2 and 3). I recognize that
theories can take many forms, and I do not
mean to imply that the structure presented
here is the only possible one. However, this
structure appears capable of embodying a
wide variety of theories within biology.
In my structure, theories are hierarchi-
cal frameworks that connect broad general
principles to highly specific models. For
heuristic purposes, I present this hierarchy
as having three tiers—a general theory,
constitutive theories, and models. Scheiner
and Willig (2008) coined “constitutive the-
ory” as a neutral term that simply indicates
that a particular theory is one constituent
of a larger framework.
In the example presented above, the
theory of evolution is the general theory,
the theory of natural selection is a consti-
tutive theory within that general theory,
and the breeder’s equation is a specific
model derived from that constitutive the-
ory. This view of theories as families of
subtheories, including models, is consis-
tent with how theories are treated across all
of biology and in other sciences as well
(van Fraassen 1980; Giere 1988; Beatty
1997; Longino 2002; Pickett et al. 2007;
Wimsatt 2007; del Rio 2008; NRC 2008).
Theories do not necessarily fit neatly
into these categories. Rather, the frame-
work will often stretch continuously from
the general to the specific. The three tiers
merely illustrate that continuum, and pro-
vide a useful way of viewing that hierarchy.
This paper focuses on general theories and
presents an overarching theory of biology,
plus five narrower, but still general, theo-
ries. I also give an example of an even
narrower general theory (multicellular or-
296 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

ganisms) nested within a broader one (all
organisms). For a discussion of the nature
of constitutive theories, see Scheiner and
Willig (2008, 2011a).
A theory defines a domain—the scope of
that theory. For the theory of evolution,
the domain is intergenerational patterns of
organismal change. For the theory of nat-
ural selection, the domain is those aspects
of that change that are caused by differen-
tial fitness. The breeder’s equation applies
specifically to changes in quantitative char-
acters.
For general and constitutive theories,
the domain delimits the boundaries within
which constituent theories or models may
be connected to form coherent entities.
The theory of natural selection tells us that
we should be able to link quantitative and
single-locus models, but it also limits those
models to ones where change is driven by
fitness differences. Without such bound-
aries, we would be faced with continually
trying to create a theory of everything. We
need to keep in mind, however, that do-
mains are conceptual constructs and that
theories may have overlapping domains.
Therefore, it is possible to build models
that combine processes of selection and
genetic drift, but such a model is then con-
tained within a constitutive theory that is
broader than the theory of natural selection.
When asked to describe a theory, we of-
ten list a set of broad statements describing
empirical patterns and processes that op-
erate within a domain, as we saw with the
theory of evolution. These broad state-
ments form a set of fundamental principles
consisting of concepts and confirmed gen-
eralizations (see Table 3 for definitions).
Fundamental principles are meant to be
broad in scope, often encompassing multi-
ple interrelated patterns and mechanisms.
Laws, in contrast, reside within constitu-
TABLE 2
A hierarchical structure of theories and its
components
General theory
Background: domain, assumptions, framework, definitions
Fundamental principles: concepts, confirmed
generalizations
Outputs: constitutive theories
Constitutive theory
Background: domain, assumptions, framework, definition
Propositions: concepts, confirmed generalizations, laws
Outputs: models
Model
Background: domain, assumptions, framework, definitions,
propositions
Construction: translation modes
Outputs: hypotheses
Tests: facts
See Table 3 for definitions of terms (from Scheiner and
Willig 2011a).
TABLE 3
Definitions of the theory components in Table 2
Component Description
Assumptions Conditions or structures needed to build a theory or model
Concepts Labeled regularities in phenomena
Confirmed generalizations Condensations and abstractions from a body of facts that have been tested
Definitions Conventions and prescriptions necessary for a theory or model to work with clarity
Domain The scope in space, time, and phenomena addressed by a theory or model
Facts Confirmable records of phenomena
Framework Nested causal or logical structure of a theory or model
Hypotheses Tested statements derived from or representing various components of the theory or model
Laws Conditional statements of relationship or causation, or statements of process that hold within
a universe of discourse
Model Conceptual construct that represents or simplifies the natural world
Translation modes Procedures and concepts needed to move from the abstractions of a theory to the specifics of
a model, application, or test
Modified from Pickett et al. 2007.
September 2010 297TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

tive theories. They are not part of the gen-
eral theories of biology, because no single
law is ever required for the construction of
all models within the domain of a given
theory. A brisk debate has occurred over
whether biology even has any laws (e.g.,
Beatty 1997; Brandon 1997; Mitchell 1997;
Sober 1997; Fox Keller 2007), and the con-
tinuing search for such laws is an impor-
tant impetus of theory change.
The fundamental principles need not
embody all assumptions, as some assump-
tions derive from other domains. If an
assumption is taken unchanged from an-
other domain, it may be unspecified within
a theory. For example, all theories in biol-
ogy take as given the conservation of mat-
ter and energy, fundamental principles in
the domain of physics. By taking as given
the fundamental principles of any other
general theory, we recognize the general
tenet of consilience—i.e., that the entire
set of scientific theories must be consistent
with each other (Whewell 1858). The deci-
sion to explicitly include particular assump-
tions as fundamental principles within a
theory depends on whether those as-
sumptions are subject to test within that
theory. Since no theory in biology would
ever test the conservation of matter, that
principle lies outside of biology’s theo-
ries.
At the lowest level of the theory hierar-
chy are models. The term “model” is used
for theories at this level because of their
particular role. Models are where the theo-
retical rubber meets the empirical road. Sci-
entific theories can encompass a wide variety
of types of models, including physical mod-
els (e.g., Watson and Crick’s ball and wire
model of a DNA molecule), as well as ab-
stract or conceptual models, which may be
analytic, statistical, or simulations. Models
are where predictions are made and hypoth-
eses are tested. Theories at this level have the
hypothetico-deductive structure that we are
more familiar with, as compared to the se-
mantic structure evinced at other levels. Be-
cause general theories consist of families of
models, they very rarely rise or fall based on
tests of any one model.
Theories play three roles (R. Creath, un-
published research). First, theories serve as
generalizations that go beyond the scope
of the specific data upon which those gen-
eralizations are based. Second, theories
provide concepts that go beyond what can
be expressed in observational terms. Both
of these roles involve theories as descrip-
tors of the world. Third, theories provide a
framework for guiding and evaluating
research—what Kuhn (1962) called a “par-
adigm” and Laudan (1977) called a “re-
search tradition.” The theories presented
in this paper play all of these roles.
The most common role of a general the-
ory is to serve as a reminder of the implicit
assumptions built into models, hypotheses,
and experiments. For an extensive discus-
sion and numerous examples of how such
reminders can improve models and exper-
iments, see Scheiner and Willig (2011b), as
to discuss this here would substantially ex-
pand an already extensive essay. I urge the
reader to investigate this further for herself
or himself, however, as the various general
theories are presented.
rules for theory construction
Before we can examine biology’s general
theories, we must consider the rules that will
be followed in their construction. First, a
general theory must potentially apply to all
species. That is not to say that the patterns
and processes embodied in those theories
apply to all organisms at all times. However,
the theories should not be about just a lim-
ited set of species. I will return to this point
when discussing the theory of organisms.
Second, a fundamental principle must ap-
ply to all or most of the constitutive theories
within the domain of the general theory.
The components of a constitutive theory
need not refer back to all of the fundamental
principles; however, those principles should
act as basic assumptions behind all of the
constitutive theories and models, and act as
links among constitutive theories.
Third, the first fundamental principle of a
theory should encompass the basic object of
interest, and all of the other parts of the
theory should serve to either explain this
central observation or to explore its conse-
quences. Thus, the first fundamental princi-
298 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

ple serves as a guide for the rest of the the-
ory.
Fourth, a fundamental principle must po-
tentially be up for falsification within the do-
main of consideration. If it is not, then the
principle belongs to another domain and is
applicable in the domain of consideration
through consilience. Falsification comes about
through the constitutive theories within that
domain.
Fifth, the set of fundamental principles of
a subsidiary theory should not simply repeat
those of a more general theory, but must be
consequences of them for that particular do-
main. Otherwise, all of the fundamental
principles of the more general theory are
assumed to hold.
Sixth, the number of fundamental princi-
ples should be as few as necessary, but no
fewer. This simplicity is achieved if each fun-
damental principle encompasses a single
concept, although that concept can itself
contain a multitude of subconcepts, pro-
cesses, or patterns. By striving toward sim-
plicity in theory structure, we are forced
to consider which concepts are most cen-
tral.
The Theory of Biology
The theory of biology is encapsulated
in ten fundamental principles (Table 4).
These principles are phrased in terms of
living systems because they apply, to one
degree or another, to the entire biological
hierarchy (Figure 1). The fundamental
principles define a domain—the diversity
and complexity of living systems, including
causes and consequences. Those causes
and consequences relate to six attributes of
living systems defined by the fundamental
principles of persistence, boundedness, in-
formation, variation, complexity, and con-
tinuity. Those attributes cause or are the
result of four processes: interaction,
emergence, change, and contingency.
Within this overarching theory are five
general theories, and, of these, two are
about hierarchical units (cells and organ-
isms  individuals), one is about an at-
tribute (genetics  information), and
two are about particular aspects of pro-
cesses (ecology  interactions of individ-
uals and populations, and evolution 
change over generations).
The first fundamental principle—persis-
tence—as with all of the theories, defines
the central observation to be explained:
that living systems are open and non-
equilibrial (von Bertalanffy 1950) and yet
manage to persist, both over the course of
a single lifetime and over aeons. “Open”
means that living systems take in and
release matter and energy. “Non-equilibrial”
means that living systems consist of or-
dered structures in a universe that other-
wise tends toward disorder. For life to
persist, order must be actively maintained.
Thus, the persistence is surprising and in
need of explanation.
The second fundamental principle—
boundedness—describes the foundation
of living systems, the cell that maintains a
pocket of order in a disordered universe
(Dutrochet 1824). The cell holds together
the complex machinery of life along with
the energy needed to power that machin-
ery. Life, if it could exist at all, would have
a very different character if it was not
bounded in this way. An alternative expres-
TABLE 4
The domain and fundamental principles of the
theory of biology
Domain
The diversity and complexity of living systems, including
causes and consequences
Principles
1. Life consists of open, non-equilibrial systems that are
persistent.
2. The cell is the fundamental unit of life.
3. Life requires a system to store, use, and transmit
information.
4. Living systems vary in their composition and structure
at all levels.
5. Living systems consist of complex sets of interacting
parts.
6. The complexity of living systems leads to emergent
properties.
7. The complexity of living systems creates a role for
contingency.
8. The persistence of living systems requires that they are
capable of change over time.
9. Living systems come from other living systems.
10. Life originated from non-life.
September 2010 299TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

sion of this idea is that life, at its founda-
tion, consists of bounded units. While
some organisms are acellular, they still ex-
ist as bounded individuals.
The third fundamental principle—infor-
mation—recognizes that life is ordered
complexity and that order contains infor-
mation (Quastler 1953). For living organ-
isms to maintain themselves, they must
have a way to capture and use the informa-
tion contained in that order.
The fourth fundamental property—vari-
ation—recognizes that living systems vary
in space and time at all levels of the bio-
logical hierarchy (Mayr 1982). This ubiq-
uity of variation separates the science of
biology from many others. For example,
physics deals with a limited number of
types of particles (e.g., protons, neutrinos,
quarks) that are the same everywhere in
the universe.
The fifth fundamental principle—com-
plexity—acknowledges that a hallmark of
living systems is that they are made up of
many different kinds of parts, arranged in
a complicated fashion and interacting with
each other in many different ways (Kolasa
and Pickett 1989). This interacting struc-
ture results in non-additive and non-linear
outcomes (Lorenz 1963). Complexity is a
direct result of life’s dynamic variation
(von Bertalanffy 1951).
The sixth fundamental principle—
emergence—is a result of the complexity
of living systems (Reason and Goodwin
1999). An emergent property is one that is
found at a certain level of organization due
to properties, structures, and processes
that are unique to that level. Emergent
properties can be contrasted with those
that are merely aggregates of properties at
a lower hierarchical level. Consider loco-
motion. A human’s ability to walk down
the street requires the existence of many
different parts—bones, muscles, connec-
tive tissues, nerves, and so forth—arranged
in a specific three-dimensional configura-
tion, and all operating together in a par-
ticular way. The separate parts cannot
move on their own, thus movement is an
emergent property of the whole organism.
Such emergent properties can be found at
all levels of living systems. The function of
a protein depends on the sequence of
amino acids and how that chain is folded
together into a precise three-dimensional
shape. Cells function by separating and
concentrating molecules into particular
subsections. Emergent properties are the
result of feedbacks within living systems.
The seventh fundamental principle—
contingency—is again a result of life’s
complexity. Contingency is the com-
bined effects of two processes: random-
ness and a sensitivity to initial conditions
(Lorenz 1963; Reason and Goodwin
1999). The dynamic nature of living sys-
tems is one factor that allows randomness
to play a role, while its complexity creates
the sensitivity to initial conditions.
The eighth fundamental principle—
change—is the recognition that the dy-
namic nature of living systems is neces-
sary for their persistence (von Bertalanffy
1950). An individual has to continually
change to survive. Change in one part of
the system creates stability in other parts.
For example, mammals and birds tend to
maintain a constant body temperature by
having an active system for converting
Figure 1. A Biological Hierarchy
One biological hierarchy extends from biomolecules
to the entire biosphere. At each level, interactions
among the units of that level, including the flow of
matter, energy, and information, result in subsystems
that are the components of the next level. All of the
attributes (persistence, boundedness, information, vari-
ation, complexity, and continuity) and processes (inter-
action, emergence, change, and contingency) of living
systems can be found at each level.
300 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

chemical energy into heat. Over much
longer periods of time, evolution is impor-
tant for the survival of a lineage. Because
the world keeps changing, a species would
go extinct if it did not evolve. Change does
not guarantee persistence, but a lack of
change guarantees eventual death or ex-
tinction.
The ninth fundamental principle—con-
tinuity—recognizes that for change to oc-
cur from one generation to the next, there
has to be continuity of living systems. That
continuity embodies two principles—that
living systems come from other living sys-
tems and that, on the whole, these new
living systems are extremely similar to the
ones that they came from. This principle is
a generalization of one of the two basic te-
nets of the old cell theory, which stated that
new cells come from old ones (Dutrochet
1824).
The tenth fundamental principle—
origins—arose during the emergence of bi-
ology as a scientific discipline in the nine-
teenth century (Ruse 1999). The organic
origins question was hotly disputed, with one
extreme position relying on the action of
miracles and the other on processes gov-
erned by natural laws. This principle does
not require that all life on Earth have a
single origin; that claim is left to the theory
of evolution (Table 1, principle 3).
Biology’s Conceptual Framework
the general theories
Within the theory of biology are five gen-
eral theories that span its domain: cells,
organisms, genetics, ecology, and evolu-
tion. Here, I briefly consider the first four
and look at their implications for the fifth.
For the sake of brevity, I do not examine
each fundamental principle; for those de-
tails, please see the Appendix.
One view of life is that it consists of a set
of controlled chemical reactions. Life ex-
ists only because it is possible to maintain
highly ordered systems against the decay of
entropy. The cell provides the wall be-
tween order and disorder. Thus, cells are
the foundational units of life (Table 4,
principle 2). The domain of the theory of
cells is the properties and causes of the
structure, function, and variation of cells.
The theory consists of ten fundamental
principles (Table 5). The first three prin-
ciples are about the molecular constitu-
ents, internal structures, and functions of
cells, and they provide links between this
theory and the theory of genetics. The next
three are about how cells interact with
their external environment. These princi-
ples provide links with the theories of or-
ganisms and ecology. The next principle is
about energy use. The final three are about
where cells and their properties come
from, and these provide links with the the-
ories of genetics and evolution. The prop-
erties of cells embodied in this theory can
be found in any textbook on cell biology
(e.g., Lodish et al. 2008).
If cells are the foundational units of liv-
ing systems, then organisms are its integra-
tive units. For single-celled organisms, they
are one and the same. Multicellular organ-
isms separate the foundational and the in-
tegrative, which is why I include a separate
subtheory dealing specifically with multi-
cellularity. The domain of the theory of
organisms consists of individuals and the
causes of their structure, function, and
variation. What constitutes an individual is
a key concept within this theory (Pepper
and Herron 2008). The theory of organ-
isms consists of ten fundamental principles
(Table 6A). The first four principles deal
with the internal structure and function of
organisms. They provide links with the the-
ories of cells and genetics. The next four
principles deal with interactions with the
external environment and provide links to
the theories of cells and ecology. The last
two principles are about the causes of or-
ganismal properties, and these link to the
theory of evolution. The theory of organ-
isms was developed with my colleague, Wil-
liam Zamer. We are currently working on a
manuscript that will provide a detailed ex-
ploration of this theory, including the
sources of its principles, although most can
be found in any introductory biology text-
book (e.g., Sadava et al. 2008; Campbell
et al. 2009).
The principles of the general theory apply to
September 2010 301TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

all organisms. Additional fundamental princi-
ples are necessary in order to account for the
special properties of multicellular organisms
(Table 6B). The theory of multicellularity con-
sists of six fundamental principles. The first
principle captures the essential feature of mul-
ticellular organisms—that is, cell specialization.
The next two principles deal with the processes
necessary for specialization to occur, and the
final three principles deal with the conse-
quences of specialization.
This subtheory of the theory of organ-
isms is an example of how theory hierarchy
can be stretched to fit one general theory
inside another. It becomes a matter of con-
vention whether one wants to call the the-
ory of multicellularity a general theory or a
constitutive theory. I consider it more than
a constitutive theory because it does not
lead directly to model building, one of the
hallmarks of a constitutive theory. How-
ever, neither is it a general theory at the
level of the others because it only applies
to a specific subset of species. I present it
here because so much of the science of
biology focuses on multicellular organ-
isms.
The order within living systems can be
described as information that is addressed
by the theory of genetics (Table 7). The
persistence of living systems means that its
information is maintained. Because the
theory of organisms states that all organ-
isms die, that maintenance must include
transmission across generations. Thus, the
domain of the theory of genetics is about
the patterns and processes of the use, stor-
age, and transmittal of information in
organisms. The theory consists of nine fun-
damental principles and derives from prin-
ciple 3 of the theory of biology (Table 4).
The general properties of genetic systems
embodied in this theory can be found in any
genetics textbook (Pierce 2007; Brooker 2008;
Lewin 2008).
The theory of ecology (Table 8) ad-
dresses the abundance and distribution of
organisms, and it consists of eight funda-
mental principles that were recently codi-
fied as the components of a general theory
(Scheiner and Willig 2008; see Scheiner
TABLE 5
The domain and fundamental principles of the
theory of cells
Domain
Cells and the causes of their structure, function, and
variation
Principles
1. Cells are highly ordered, bounded systems.
2. Cells are composed of heterogeneous parts consisting
of subsystems that act to localize resources and
processes.
3. Cells are regulated by a network of biochemical and
supermolecular interactions.
4. Cells interact with their external environment,
including with other cells.
5. Cells exchange matter through boundaries consisting of
semipermeable membranes.
6. Cells require an external energy source, either chemical
or electromagnetic.
7. Cells use energy to create concentration gradients of
ions and molecules.
8. New cells are formed from other existing cells.
9. Cells contain all of the information necessary for their
own construction, operation, and replication.
10. The properties of cells are the result of evolution.
TABLE 6A
The domain and fundamental principles of the
theory of organisms
Domain
Individuals and the causes of their structure, function, and
variation
Principles
1. An individual organism actively maintains its structural
and functional integrity.
2. All organisms are composed of cells at some point in
their life cycle.
3. Organismal maintenance at one level requires change
at other levels.
4. Organismal functions trade-off against each other.
5. Organismal maintenance is a function of interactions
with the abiotic and biotic environment.
6. Organisms require external sources of materials and
energy for maintenance, growth, and reproduction.
7. Because organisms are changeable, external influences
can force change.
8. Heterogeneity of resources in space and time leads to
variation in ontogeny and life history patterns.
9. Organismal reproduction is both a cause and
consequence of evolutionary processes.
10. The properties of organisms are the result of evolution.
302 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

and Willig 2011a for a more detailed ex-
ploration of this theory). The theory as
presented here is the result of numerous
conversations that we had with our col-
leagues in producing the predecessor pa-
per and the subsequent book. See those
sources for a detailed exploration of the
sources of these principles.
During the process of developing these
theories, various principles were reformu-
lated or swapped between theories, so as to
make them consistent with each other and
with the rules for theory construction that
I put forth earlier in this paper. This pro-
cess is one reason for the differences in the
theory of ecology as put forth in Scheiner
and Willig (2008) and Scheiner and Willig
(2011a).
I make no claim that these fundamental
principles are entirely novel. Quite the
contrary, all of them can be found in many
biology textbooks. What is new here is the
extraction of these principles into clear,
simple statements that constitute the core
set of concepts in biology.
the theory of evolution, redux
Returning to the theory of evolution in
light of the other general theories, we see
that the fundamental principles dealing
with the mechanisms of evolution (Table
1, principles 4–7) are dependent on the
other theories for their meaning. Funda-
mental principles 4 and 5—gradualism
and variation—link to the theories of ge-
netics, cells, and organisms to provide the
mechanisms for generating variation and
change. Fundamental principle 6—natu-
ral selection—links to the theories of organ-
isms, ecology, and genetics. Fundamental
principle 7—contingency—links to the the-
ories of genetics (genetic drift) and ecology
(historical contingency). Thus, everything in
evolution makes sense only in light of the
rest of the biology of the organism. In my
framework, the theory of evolution no
longer holds center stage.
In my explication of the other theories, I
have moved some of the issues previously
considered to be part of the theory of evo-
lution—notably, the role of inheritance—
out of that theory. Another way of saying
this, rather than viewing the Modern Syn-
thesis as the incorporation of Mendelian
genetics into evolution, is that this process
was the development of a parallel theory of
genetics that linked to and informed evo-
lutionary theory.
Recently there have been calls for the
replacement of the theory of evolution, as
articulated by the Modern Synthesis, with a
version in which development is given cen-
tral stage (Hull 2006). In the context of the
TABLE 6B
The fundamental principles of the subtheory of
multicellular organisms
Principles
1. Multicellularity allows for specialization of cells.
2. Cell-cell interactions are necessary for cell specialization.
3. Specialization of cells requires their spatial or temporal
localization at some point in the life cycle.
4. Specialization of cells leads to emergent organismal
properties.
5. Specialization of cells allows for modularity.
6. Development requires heterogeneity in cellular or
organismal composition.
TABLE 7
The domain and fundamental principles of the
theory of genetics
Domain
The patterns and processes of the use, storage, and
transmittal of information in organisms
Principles
1. Offspring resemble their parents.
2. The fidelity of information transmittal requires an error
correction system.
3. Because life is the product of natural selection, the
information system must be capable of producing new
information.
4. The imperfections of error correction create new
information.
5. The exchange and recombination of information among
individuals create new information.
6. Random processes play an important role in information
transmittal, error correction, and the exchange of
information among individuals.
7. The system of information usage must be robust to
errors.
8. Information usage is context dependent.
9. The properties of information systems are the result of
evolution.
September 2010 303TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

theory presented here, this change could
involve the addition of a fundamental prin-
ciple about the role of development in de-
termining phenotype and the pathways of
evolutionary change. However, because de-
velopment is a process confined to multi-
cellular organisms, such an evolutionary
theory would not be general. Instead, that
new principle would have to be a more
general statement about the link between
genotype and phenotype. Such a principle
would have to encompass processes other
than those contained in principle 8 of the
theory of genetics (Table 7), which states
that information usage is context depen-
dent. Another way to state the issue is that
the insights provided by evo-devo do not
overturn the theory of evolution; rather,
they add to our understanding of its fun-
damental principles, as well as to how that
theory links to the other general theories.
unified theories in biology
There is extensive precedence in biology
for the development of unified theories.
For example, at the turn of the twentieth
century, Wilson (1896) put forth a theory
of cells and organisms grounded in what
he saw as the two general theories of biol-
ogy—cell theory and evolutionary theory.
The architects of the Modern Synthesis
sought to unify biology through evolution
(Huxley 1942; Dobzhansky 1964; Smocovi-
tis 1996), and, more recently, metabolic
theory has been touted as a general expla-
nation for the properties of living systems
(West et al. 1997; Allen et al. 2002; Brown
et al. 2004).
Often the goal in developing such theo-
ries is to produce a single explanation for
living systems. My goal is quite different. In
my hierarchical framework, each theory
encompasses a family of subtheories, so
that explanation is embedded throughout.
There is no single explanation. This plu-
ralistic view of theories is similar to that of
Longino (2002).
How to Be an Iconoclast
The conceptual framework just outlined
provides a context for our research enter-
prise. First, it allows us to define what is
meant by bold research. A bolder study
addresses a broader domain or a more gen-
eral theory. I urge you to consider your
own research within the framework just
outlined, and to use that framework to
make your work bolder by attempting to
directly address fundamental principles.
Most science is centered at the level of
constitutive theories and models, and does
not often address general theories directly.
This is not to say that these efforts do not
have implications for general theories;
however, most of the time, they take the
fundamental principles as fixed assump-
tions and examine how they play out
within narrower domains. In doing so, they
help to solidify the generalizations repre-
sented by those fundamental assumptions.
Sometimes the purpose of a study is to
help establish an unconfirmed principle.
Such work is often viewed as exploratory
because its purpose is to find enough in-
stances of a phenomenon to either show
that it is widespread or to establish the
generality from its many instances. It is
often claimed that such exploratory work is
theory- or hypothesis-free. A conceptual
framework makes clear the way in which
TABLE 8
The domain and fundamental principles of the
theory of ecology
Domain
The spatial and temporal patterns of the distribution and
abundance or organisms, including causes and
consequences
Principles
1. Organisms are distributed unevenly in space and time.
2. Organisms interact with their abiotic and biotic
environments.
3. Variation in the characteristics of organisms results in
heterogeneity of ecological patterns and processes.
4. The distributions of organisms and their interactions
depend on contingencies.
5. Environmental conditions are heterogeneous in space
and time.
6. Resources are finite and heterogeneous in space and time.
7. Birth rates and death rates are a consequence of
interactions with the abiotic and biotic environment.
8. The ecological properties of species are the result of
evolution.
304 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

theory drives such exploration. By being
able to explicate the scope of the domain
being explored, the potential importance
of the work becomes more evident.
Less frequently, a study aims to put forth
a new fundamental principle. Sometimes
these come only after the accumulation of
sufficient examples to suggest a general
principle, but sometimes they arrive as
bold new ideas (e.g., the neutral theoy of
evolution; Kimura 1954). The riskiest and
most iconoclastic research is that aimed at
disconfirming an established principle.
Having a clearly articulated theory makes it
easier to identify principles that might be
vulnerable, and makes being an iconoclast
a conscious decision. Eldredge and Gould
(1972) were very aware of what they were
doing when they attempted to disconfirm
evolution’s principle of gradualism. Be-
cause fundamental principles are general-
izations rather than laws, overturning a
fundamental principle can rarely be ac-
complished by a single observation; gener-
alization allows for exceptions. Being aware
of the structure and nature of theory can
help an iconoclast plan her attack.
New Insights
the value of a framework and
principles
At this point you may be asking yourself,
“So what have I learned? Didn’t I know all
of this already?” Well, yes and no. Often
the sorts of generalizations embodied in
fundamental principles are obvious only
after their explication. Fundamental prin-
ciples should appear to be obvious once
explicated because they are supposed to be
statements about confirmed generaliza-
tions and, as thus, well-accepted concepts.
It is only during the process of proposing
new fundamental principles that they will
seem unfamiliar.
Generalizations serve as reminders about
assumptions contained in lower-level theo-
ries. The problem with many assumptions is
that they are unstated, even subconscious, in
nature, and sometimes such unstated as-
sumptions can turn around and bite us. For
example, most models of life history evolu-
tion assume that organisms can always adopt
the optimal phenotype, instantaneously real-
locating resources from growth to repro-
duction, and so ignoring evolutionary
and developmental constraints. Ignoring
these assumptions leads to predictions that
are biologically improbable—e.g., that an or-
ganism should allocate 100% of its resources
to reproduction one day after it devoted
100% of its resources to growth (Schaffer
1983), or that an annual plant should switch
multiple times between growth and repro-
duction (King and Roughgarden 1982).
Making such assumptions explicit may
change the focus of a theory. For example, a
fundamental principle in ecology is that eco-
logical processes depend on contingencies.
Yet many ecological theories and models are
deterministic, ignoring the role of contin-
gency or stochasticity in molding patterns
and processes in nature. Deterministic mod-
els are not wrong, just potentially incom-
plete. Sometimes ignoring contingencies has
no effect on model predictions, but, at other
times, the consequences can be profound.
As the statistician George E. P. Box is re-
puted to have said, “Essentially, all models
are wrong, but some are useful.”
We should not underestimate the simple
value of a fully articulated conceptual frame-
work for biology. By itself, it provides a
structure within which we can organize our
ideas and frame debates. By revealing the
scope of theories (Figure 2), it both indi-
cates linkages among theories and possible
gaps. Those linkages occur both at the
level of fundamental principles (e.g., the
evolution principles that appear in the
other theories) and at the level of consti-
tutive theories (e.g., the roles of develop-
ment, ecology, and genetics in the theory
of natural selection).
Articulating a theory forces us to provide
clear definitions of concepts that have of-
ten been in dispute. Theories can evolve
through a change in our understanding of
a principle, without changing the way the
principle is worded (e.g., our understand-
ing of the concept of mutation was recently
broadened to include epigenetic changes;
Gonzalgo and Jones 1997; Scheid et al.
1998; Laird and Jaenisch 1996). Because
September 2010 305TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

concepts evolve, they must always be clearly
defined so as to prevent scientists from
talking past each other. Such misunder-
standings are less likely if we have formal-
ized definitions to which we can point.
Nearly all of the general domains contain a
foundational concept that has been de-
bated over decades and whose meaning
continues to be the subject of discussion.
Evolution has “species” (e.g., Hey 2001;
Reydon 2005), ecology has “community”
(Gleason 1926; Clements 1937; Fauth et al.
1996), genetics has “gene” (Portin 1993;
Beurton et al. 2000), and organismal biol-
ogy has “individual” (Pepper and Herron,
2008). Interestingly, I have not been able
to identify a similar debate over the mean-
ing of a foundational concept in the realm
of cell or molecular biology, although
those realms certainly have seen plenty of
other types of debates over concepts and
theories.
biology’s fundamental questions
The theory of biology and its five com-
ponent general theories define six ques-
tions that make up the core of the science
of biology:
1. Why does life manage to persist? (Biol-
ogy)
2. What is the cause of organismal change
and diversity? (Evolution)
3. Why do offspring resemble their par-
ents? (Genetics)
4. How does a cell maintain its structure
and function? (Cells)
5. How does an individual maintain its
integrity? (Organisms)
6. What explains the distribution of or-
ganisms? (Ecology)
These questions are restatements of the
first fundamental principles of each the-
ory. All research within biology eventually
leads back to these questions in one form
or another. Recognizing that biology has
such fundamental questions, and that they
have not changed since the origins of the
discipline, can help to ground our science
at a time of unprecedented growth and
change driven by large technological ad-
vances (NRC 2009).
comparisons among theories
Some interesting observations come from
comparisons among the theories. First,
evolution appears as an explicit funda-
mental principle in all of the other the-
ories, but the reverse is not true. The
other theories link to evolution only
through the constitutive theories that de-
rive from the principles that deal with
evolutionary mechanisms.
Second, contingency does not appear as
an explicit fundamental principle in the
theories of cells or organisms, whereas it
does in the theories of evolution, genetics,
and ecology. In the former theories, al-
though contingency may play a central role
in particular constitutive theories or mod-
els, its importance does not rise to the level
of a fundamental principle. Most constitu-
tive theories within those domains need
not reference contingent processes, and
their models can assume a lack of contin-
gency without compromising their predic-
tive or explanatory accuracy. Recognizing
this difference among the theoretical do-
mains helps explain why statistics is used
and appreciated very differently by scien-
tists working in different fields. It also ex-
plains the dominance of model organisms
in molecular, cell, and organismal biology
but not elsewhere, as well as possible dif-
ferences in attitudes concerning the extent
Figure 2. Scope of the Theories
The scopes of the five general theories of biology in
relation to a biological hierarchy based on the flow of
matter and energy. Four of the five theories encom-
pass the level of individuals, thus emphasizing the
organism-centeredness of the science of biology.
306 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

of competition and collaboration among
scientists working in different fields.
Third, the theory of genetics never men-
tions genes or DNA. It is different from the
others in that it is the least tied to specifics
of living systems on Earth. Its first principle
is the only one to directly tie it to biological
entities: parents and offspring. Most of its
fundamental principles are couched in
terms of information systems and proper-
ties that can apply equally to non-DNA
based systems and even non-living systems.
Frank (2009) provides an example of how
treating genetics as an information system
abstracted from its biology can lead to new
insights about evolution.
Recognizing the potential non-biological
nature of the theory of genetics leads to
new questions about its potential similarity
to theories of other information systems,
such as cybernetic or cultural (e.g., Wilson
2002; Mesoudi 2007). The answers to those
questions will depend on what aspects of
the information system are necessary prop-
erties of biology and nucleic acids—prop-
erties that are not shared by other types of
information systems. Such a comparison
would highlight the unique properties of
those other systems. The formalization of a
theory of genetics will help to bring those
similarities and differences into sharp re-
lief.
Fourth, the individual is the level within
the biological hierarchy where four of the
five theories overlap in scope (Figure 2),
thereby justifying an organism-centric ap-
proach to biology and its general theories.
For example, ecologists have disagreed
about whether organisms are the central
object of study in ecology. In the realms of
molecular, cellular, and organismal biol-
ogy, this organism centrality affirms the
new synthetic approaches that are attempt-
ing to reconstruct whole systems following
many decades of reductionism (Kitano
2002; Ideker et al. 2001).
Teaching Biology
Unfortunately, we have a strong ten-
dency to teach biology as a very long list of
facts, rather than as a set of theories. Just
take a look at any of the current introduc-
tory biology textbooks; nor are upper-level
textbooks much better, and I will not ex-
cept myself from this criticism (Gurevitch
et al. 2006). Sometimes those facts are
called “concepts,” but they still come across
as an extensive laundry list of details. This
approach contrasts markedly with the
other natural sciences, all of which start
with theory and then work toward the facts.
In part, this tendency is a natural outcome
of the domain of biology. Living systems
are diverse and complex. We biologists
tend to be fascinated with that diversity
and complexity and want to convey our
excitement to our students.
Teaching from a well-articulated set of
theories can change the way we approach
that task (NRC 2003). Instead of assuming
that students will induce generalizations
from the welter of detail, we should give
them the big ideas up front. The theories
would prioritize those big ideas, so that
students would know where to focus and
what they need to remember. It would help
students see the connections among the
parts of biology, in both introductory and
upper-level courses. Those links would be
explicit both by constant reference back to
the overarching attributes and processes
(e.g., complexity and change), and through
explicit use of fundamental principles
from other parts of biology (e.g., principles
about the dynamic nature of cells and in-
dividuals when discussing ecological inter-
actions). In short, theory gives unity to that
diversity.
Taking a theoretical approach to teach-
ing makes it easier to show how knowledge
comes about. A general theoretical frame-
work will encourage all of us to make ref-
erence to and use the constitutive theories
within each domain. This, thus, makes bi-
ological knowledge more dynamic and ten-
tative, not the received wisdom that our
students typically assume. Such a change
will not be easy for our students. I know
from experience that they often have little
use for the history of science and where
our knowledge came from. It is the Joe
Friday method of learning—“Just the facts,
ma’am.”
Recently, there have been numerous
September 2010 307TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

calls for pedagogical reform across all of
the sciences, especially in order to make
classes more dynamic and interactive (e.g.,
Ebert-May et al. 1997; NRC 2003; Allen and
Tanner 2005; Smith et al. 2005). The dy-
namic of science is theory generation and
hypothesis testing, and having an explicit
theoretical framework will enhance the
students’ appreciation of that dynamic.
Next Steps
I make no claims that the theories pre-
sented here are complete, that all of the
fundamental principles are correct in
whole or in part, or that the fundamental
principles are necessary and sufficient to
account for all of the constitutive theories
within each domain. My level of uncer-
tainty is greatest for the theory of cells, the
area of biology that I know the least about.
For an example of how a theory can evolve
or vary, compare the theory of ecology as
presented in Scheiner and Willig (2008)
with Scheiner and Willig (2011a) and with
this essay.
Are these the right theories? Have I
carved up the discipline of biology prop-
erly? Although theories and their domains
are to some extent arbitrary, they divide
along what appear to be natural fault lines.
But not all attributes, processes, or hierar-
chical levels are represented by a separate
theory, suggesting the potential for addi-
tions or substitutions, particularly the latter
if the theories are supposed to avoid re-
dundancy.
Among the various attributes of living
systems in the overarching theory (Table
4), only information has its own theory.
What about other attributes? One often
hears reference to complexity theory and
systems theory. Are these possible alterna-
tives? I argue that they are not.
A theory works best when it has a clear
central question or observation that it ad-
dresses. The observation can be very gen-
eral (e.g., the resemblance of parents and
offspring), in which case the theory will be
general and will contain numerous consti-
tutive theories and models aimed at subsid-
iary questions. Complexity theory (Reason
and Goodwin 1999) and systems theory
(von Bertalanffy 1951) do not have such
central questions within the domain of bi-
ology. Instead, they are collections of tools
used to address questions about interac-
tion structures raised by various biological
theories (Wolkenhauer 2001). Complexity
theory and systems theory reside within the
domain of mathematics, where they ad-
dress questions about the behavior of ab-
stracted networks.
On the other hand, recognizing that
complexity and interactions are ubiquitous
across all of biology encourages us to ex-
amine models developed in one biological
domain for possible application in other
domains. Complexity theory and systems
theory tell us how to translate those models
across domains. An important type of in-
terdisciplinarity is the importation of tools
from across disciplinary boundaries.
What about a theory dealing with other
processes? None of the theories address a
single process in all its manifestations. The
process of change is represented only by evo-
lution—change across generations. Other
types of change (e.g., developmental change
of organisms, successional change of com-
munities) are addressed by more specific
constitutive theories. Again, I argue that
what is being explained by each of those
constitutive theories is so different that a sin-
gle general theory of change could not be
devised. But I am quite willing to be proven
wrong.
What about seemingly missing theories?
Where are the theories of the origin of sex,
island biogeography, development, repro-
duction, individuality, cell-cell signaling, or
the endothelial origin of stem cells? All of
these are constitutive theories within the
general theories. The list of such constitu-
tive theories is legion. My neglect of them
here is not to discount them; rather, my
hope is that this paper will encourage oth-
ers to draw those theories into coherent
frameworks. That is no simple task. Even
an entire book (Scheiner and Willig 2011b)
fails to capture the entire domain of ecol-
ogy.
My theoretical framework cries out for
historical analyses. The history of the the-
ory of evolution has been examined much
308 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

more extensively than theories in other
parts of biology. An articulated conceptual
framework can help guide such historical
analyses. Philosophical analyses are equally
needed and would put this current list of
fundamental principles in context, possi-
bly revealing other overarching aspects of
living systems.
Conclusions
It is appropriate that these general bio-
logical theories be explicated during the
sesquicentennial of On the Origin of Species.
This project reveals that biology is a theory-
rich discipline, a fact that is often not
recognized and sometimes denied. For ex-
ample, within organismal biology, the word
“theory” is rarely used to describe ideas,
despite the fact that it contains a large
number of well-developed constitutive the-
ories. Conversely, ecology is awash with a
welter of seemingly contradictory theories.
The development of theory frameworks
can tame this debate by organizing theo-
ries into coherent structures (e.g., Schei-
ner and Willig 2011b).
This process of theory explication is evo-
lutionary rather than revolutionary, a direct
continuation of the process that occurred
during the Modern Synthesis (Smocovitis
1996). Much of this process is the formaliza-
tion of ideas that have been around for a
long time, but some are new, resulting from
being forced to confront all aspects of biol-
ogy when developing general theories. For
example, our explication of a theory of or-
ganisms led William Zamer and me to con-
sider why individuals die and reproduce
(Table 6A, principles 7 and 9).
A recent attempt to look at theory
broadly across all of biology resulted in a
document by the National Research Coun-
cil (2008) that was rich in models but de-
ficient in general theories. My efforts here
are, in part, a direct reaction to that exer-
cise. It is clear to me that the structure and
function of general theories are not well
understood by most biologists. This paper
should advance that understanding.
My hope is that this essay will lead to a
vigorous discussion and debate across all of
biology, and past history gives us some
hints about the possible nature of that de-
bate. The hardest decision concerning the
content of a general theory is not whether
a fundamental principle is true, although
that can lead to a vociferous debate, but
whether it is general enough to rise to the
level of a fundamental principle. For exam-
ple, in the theory of evolution, the debate
over the role of contingency (Table 1, prin-
ciple 7) was not about contingency, per se,
but about whether the process was impor-
tant enough to be a fundamental princi-
ple.
I emphasize that these debates should be
over meaning, not wording. I have a pref-
erence for simple, jargon-free language,
and I tried to express the fundamental
principles in that way, but I would not go to
battle over word choices. On the other
hand, I have and will argue over their con-
tent.
In honor of Darwin’s bicentenary, I end
with this thought. There is grandeur in this
view of life, with its entangled bank of theo-
ries both general and specific. From so sim-
ple a beginning, endless models most won-
derful have been, and are being, evolved.
acknowledgments
I thank the many colleagues that have provided feed-
back and comments on these ideas and this manu-
script: Dan Dykhuizen, Gordon Fox, Conrad Istock,
Norm Johnson, Jurek Kolasa, Jane Maienschein,
Daniel McShea, Adam Porter, Kayla Scheiner, Betty
Smocovitis, Art Weis, John Weins, Mike Willig, Bill
Zamer, and an anonymous reviewer. These ideas were
inspired by Jim Collins and his push to enhance the
role of theory in biology. The theory of cells derives
from an exercise done with my colleagues at the
National Science Foundation in which I challenged
them to come up with fundamental principles for
such a theory; those results were then synthesized by
me. The manuscript benefited greatly by my partici-
pation in the MBL-ASU History of Biology seminar on
Theory in Biology. I worked on the manuscript while
on sabbatical at the Center for Environmental Sci-
ences and Engineering of the University of Connect-
icut, the University of South Florida, the University of
Florida, and the Koffler Scientific Reserve at Jokers
Hill of the University of Toronto, and I thank all of
my hosts. This manuscript is based on work done
while serving at the National Science Foundation.
The views expressed in this paper do not necessarily
September 2010 309TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

reflect those of the National Science Foundation or
the United States Government.
Appendix: Fundamental Principles
Table 5. The Theory of Cells
The first fundamental principle—bounded-
ness—recognizes that a cell is defined by its lipid
membrane (Lintilhac 1999). That membrane al-
lows a cell to maintain an internal environment
that differs from its external environment—in
particular, it concentrates and organizes chemical
processes. A membrane sets the stage for two
types of feedback systems: those internal to the
cell, and those between the cell and its exterior.
The internal feedback system keeps the chemical
reactions in balance. A cell also needs to maintain
itself in the face of a changing external environ-
ment, and it is able to do so because its membrane
is selectively permeable. A cell is not at equilib-
rium with its surroundings, and maintaining that
non-equilibrial state requires energy. If a cell is
part of a multicellular organism, the membrane is
a critical component of the signaling system
among the cells. Many of the other fundamental
principles relate to these consequences of mem-
brane properties.
The second fundamental principle—heteroge-
neous subsystems—recognizes that cells are
highly structured in ways that increase the effi-
ciency of cellular functions. Rather than watery
bags of chemicals, they are viscous solutions—
more Jell-O™ than Kool-aid™. The efficient func-
tioning of a cell is, thus, an emergent property of
this structure. This cellular sub-structuring was
recognized in the nineteenth century (Wilson
1896), although the details of that structure
are still being elucidated today. This principle
is the cellular manifestation of variation and
emergence in complex systems (Table 4; prin-
ciples 4, 5, and 6).
The third fundamental principle—regulated
networks—represents the dynamic consequences
of the physical complexity embodied in the pre-
vious principle (Proulx et al. 2005; Costanzo et al.
2010). A cell is a dynamic entity; parts are contin-
ually being assembled, disassembled, and re-
assembled for other functions. The chemical
reactions must be controlled. Complex physical
structures support the intricate network of chem-
ical reactions that undergird living systems. This
principle is at the heart of the newly emerging
field of systems biology and is the cellular mani-
festation of the interaction principle (Table 4,
principle 5).
The fourth fundamental principle—external
interactions—indicates that cells are open
rather than closed systems. The cell membrane
is the gateway that regulates these interactions.
These gateways can be passive or active and can
involve the movement of energy, materials, and
information across the membrane (Lodish et al.
2008).
The fifth fundamental principle—semiper-
meable membranes—establishes one of the
primary mechanisms by which the cell ex-
changes matter and interacts with its external
environment. The semipermeability of the mem-
brane is a key property that helps to maintain the
non-equilibrium state of the cell (Philippson 1921).
The sixth fundamental principle—external
energy—establishes one of the other primary
external interactions. Living systems maintain
themselves in an ordered state by using en-
ergy which must come from an external
source (Lodish et al. 2008).
The seventh fundamental principle—con-
centration gradients—embodies a central use
for that energy, one of the primary mechanisms
that cells use both to maintain order through
boundary membranes, and to organize chemi-
cal reactions on internal membranes (Griffiths
2007).
The eighth fundamental principle—new cells
from old—is one of the two central tenets of the
original cell theory from the nineteenth cen-
tury (Dutrochet 1824), the other being that all
organisms are composed of cells. Here, I sepa-
rate these two components into one part that
concerns cells and another part that concerns
organisms. The promulgation of the old theory
of cells was part of the general development of
biology as a discipline in the nineteenth cen-
tury. This principle is the cellular version of
principle 9 of the theory of biology (Table 4).
The ninth fundamental principle—informa-
tion location—indicates that cells, as funda-
mental units, are also the places where the
information described in the theory of genetics
resides (Morgan 1917). To say that cells contain
all of the necessary information does not
conflict with the notion that the use of that
information is at least partially dependent on
external factors (see below). Rather, it is a state-
ment that that information, at the very least,
consists of DNA sequences arranged into chromo-
somes. The development of the chromosomal
theory of inheritance in the early twentieth cen-
tury was an important step toward the emergence
of molecular biology.
The tenth fundamental principle—proper-
ties through evolution—is the result of pro-
cesses that derive from the theory of evolution.
Evolution is often touted as the central organiz-
310 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

ing theory of biology. Rather, the theory of
biology is a set of general theories that consist
of overlapping and interacting domains, all of
which inform each other.
Table 6A. The Theory of Organisms
The first fundamental principle—integrity—
captures the central observation that individuals
actively maintain their structure and function.
Such integrity serves to separate self from non-
self, both from the abiotic environment as well
as from other individuals. This principle paral-
lels the first fundamental principle of cells
(boundedness), but differs in that the bound-
aries of individuals are not always as easily
characterized (Pepper and Herron 2008). This
principle is the organismal version of persis-
tence (Table 4, principle 1).
The second fundamental principle—cells—
recognizes that all organisms are composed of
cells at some point in their life cycle (Dutrochet
1824). Indeed, most organisms consist of cells
all of the time, some being unicellular and oth-
ers multicellular. Other organisms (e.g., slime
molds, many fungi) are acellular, consisting of a
single entity with multiple nuclei; however, at
some point in their life cycle, usually as part of
the reproductive process, individual cells are
produced. This principle is the other central
tenet of the old cell theory.
The third fundamental principle—change—
encapsulates the primary mechanism by which
organismal integrity is maintained. Organisms
are dynamic entities (Sadava et al. 2008; Camp-
bell et al. 2009). They vary in their biochemical
composition from second to second as they re-
act to environmental stimuli. From year to year,
they vary in their morphological structure as
they grow and develop. This dynamic results
from a complex web of positive and negative feed-
backs that creates a role for contingency in organ-
ismal structure and function. This principle is the
organismal manifestation of the change over time
principle (Table 4, principle 8).
The fourth fundamental principle—trade-
offs—recognizes that no organism is able to do
everything. This principle forms the basis of
many constitutive theories (e.g., Roff 1992).
The existence of trade-offs drives phenotypic
variation through niche differentiation—an in-
stance of the intersection of the theory of
organisms with the theories of ecology and evo-
lution. This intersection demonstrates how some
constitutive theories straddle the domains of gen-
eral theories. For example, models of the evolu-
tion of phenotypic plasticity depend equally on
trade-offs in organismal function, the ecological
structure of metapopulations, and evolutionary
dynamics (for reviews see Scheiner 1993; Berri-
gan and Scheiner 2004). This is the organismal
manifestation of the interaction principle (Ta-
ble 4, principle 5).
The fifth fundamental principle—external
interactions—is the organismal equivalent of
the fifth principle of the theory of cells. Organ-
isms interact with their external environments
in a variety of ways (Sadava et al. 2008; Camp-
bell et al. 2009). Electromagnetic energy (light
and heat) flows in and out of organisms. Organ-
isms obtain information from the environment
through a variety of types of sensors that re-
spond to many different kinds of stimuli, such
as electromagnetic energy (e.g., sight), chemi-
cals (e.g., taste and smell), and gravity (e.g.,
root geotropism). Information exchange can
include signals among conspecifics or with
other species. Individuals also have physical in-
teractions, and these can be both positive and
negative and both within and between species.
This principle, thus, forms the basis for large
swaths of the constitutive theories that make up
organismal biology.
The sixth fundamental principle—materials
and energy—highlights a key interaction be-
tween an organism and its environment (Sa-
dava et al. 2008; Campbell et al. 2009), again
paralleling the principles of the theory of cells.
The second law of thermodynamics requires
that organisms lose energy when they use it to
perform functions—functions that are required
because organisms are dynamic (principle 3).
That energy often comes packaged in organic
molecules. Even autotrophs must build struc-
tures to capture energy in the form of light or
heat. When organisms reproduce, they must
build new structures.
The seventh fundamental principle—forced
change—deals with a central property of living
systems: they are mortal. That is, no organism is
invulnerable; any organism might die as the
result of predation, stress, trauma, or starvation.
Death comes about through environmental in-
teractions. Obviously, principle 6 implies that
any organism can be starved of materials and
energy. Not as obviously, principle 3 implies
that the dynamics of an organism can be dis-
rupted. Only an inert object can potentially
avoid external change. This vulnerability ap-
pears to be inherent in the carbon-based life
found on Earth and may be true of any living
system, whatever its chemical or energy basis.
This principle does not mean that all organisms
senesce. There is evidence that some animals
do not, nor has senescence been demonstrated
September 2010 311TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

in plants (Roach and Gampe 2004). The senes-
cence of organisms is a narrower version of this
principle that applies to particular constituent
theories.
The eighth fundamental principle—ontogeny—
accounts for the vast diversity that we see in the
tempo and mode of organismal growth, repro-
duction, and mortality (Roff 1992). The devel-
opment of multicellular organisms is a subset of
these processes. This principle is another man-
ifestation of the change over time principle (Ta-
ble 4, principle 8).
The ninth fundamental principle—repro-
duction—addresses a fundamental characteris-
tic of all organisms: they reproduce sexually or
asexually at some point in their life cycle. But
why shouldn’t organisms simply grow indefi-
nitely? If all organisms are the result of evolu-
tion (principle 10), they must reproduce. The
primary driving process of evolution is natural
selection (Table 1, principle 6), and natural
selection acts on heritable variation among in-
dividuals. The generation of heritable variation
occurs through a combination of mutation and
recombination (see the theory of genetics, be-
low). Even organisms that reproduce strictly
asexually generate variation through the accu-
mulation of mutations. If organisms did not
reproduce, variation would not be generated,
and the processes of evolution and natural se-
lection would grind to a halt. Thus, evolution
implies reproduction. This is the organismal
version of principle 9 of the theory of biology
(Table 4).
As with the theory of cells, the tenth funda-
mental principle—evolution—is the result of
processes that derive from the theory of evolu-
tion. It forms the basis for disciplines such as
comparative physiology. This principle may
seem obvious, but even today many organismal
studies are not comparative, and even those
that are do not necessarily use a phylogenetic
framework. The need to use a phylogeny is an
example of how a fundamental principle can
continually prod the assumptions that may lie
hidden within a study.
Table 6B. Multicellular Organisms
The first fundamental principle—cell special-
ization—highlights a feature of nearly all multi-
cellular organisms—i.e., that they consist of more
than one cell type. Such specialization allows us to
distinguish a multicellular individual from a mere
collection of cells. Specialization leads to in-
creased functionality and efficiency because it
breaks the trade-offs (principle 4 of the theory of
organisms) caused by having to perform multiple
functions simultaneously or with the same set of
structures. For example, Solari et al. (2006) pos-
tulated that within volvocine algae, the evolution
of multicellularity was due to a trade-off between
flagellated cells necessary for colony buoyancy
and non-flagellated, reproductive cells. The evo-
lution of animals and plants can be modeled as an
increase in the number of cell types (Hedges et al.
2004). This principle derives from the variation
principle of the theory of biology (Table 4, prin-
ciple 4).
The second fundamental principle—cell-cell
interactions—addresses the first mechanism
necessary for cell specialization. In order for
cells to specialize in an orderly fashion, they
must be able to communicate (Lodish et al.
2008). This principle provides a link with the
theory of cells and derives from the interaction
principle (Table 4, principle 5).
The third fundamental principle—localization—
addresses the second specialization mechanism
(Gilbert 2006). If multicellular organisms con-
sist of specialized cells, those cells either exist at
particular points in a life cycle (e.g., spores) or
are spatially separated (e.g., tissues and organs).
This principle is another example of biology’s
variation principle (Table 4, principle 4).
The fourth fundamental principle—emer-
gence—addresses the new properties that come
from cell specialization. The existence of mul-
tiple cell types and their spatial or temporal
localization allow for emergent properties (Gil-
bert 2006). This principle is the organismal
manifestation of the emergence principle (Ta-
ble 4, principle 6).
The fifth fundamental principle—modular-
ity—addresses another property of multicellular
organisms. One difference between unicellu-
lar and multicellular organisms is that the
latter have the potential for modularity (e.g.,
leaves, limbs, body segments). Modularity al-
lows for more extensive differentiation and
the spatial separation of cell functions. It also
permits greater evolutionary independence
of the parts by breaking pleiotropic and epi-
static correlations among genes (Wagner
1989; West-Eberhard 2003; Hansen and Houle
2008). Again, this principle derives from the
variation and interaction principles (Table 4,
principles 4 and 5).
The sixth fundamental principle—develop-
ment—addresses another consequence of mul-
ticellularity. Development is the determination
of cell fate, cell differentiation, and morpho-
genesis. By definition, development can occur
only in multicellular organisms. Some unicellu-
lar organisms undergo ontogenetic change,
312 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

such as Bacillis subtillus that can switch between
a metabolically active state and a resting or
spore state. While that process is often referred
to as development (e.g., Losick and Stragier
1992), I distinguish it from true development.
All development requires the existence of
some sort of asymmetry (Gilbert 2006), either
within a single cell (e.g., a fertilized egg) or an
organism (e.g., gradients of morphogens in a
Drosophila larva). These asymmetries are what
allow for cell differentiation to occur in an or-
dered fashion.
Evolutionary theory treats the source of phe-
notypic variation and the genotype-phenotype
link as a black box. This principle shows that
the explanation for phenotypic variation in
multicellular organisms comes from a theory of
development embedded within a theory of or-
ganisms, which, in turn, exists as a complement
to the theory of evolution (Gilbert and Epel
2009).
Table 7. The Theory of Genetics
The first fundamental principle—resemblance
of relatives—establishes the fact that relatives
are similar to each other. However, resem-
blance is not identity, and the theory of genetics
is as much about why relatives do not resemble
each other as why they do. This principle sub-
sumes within it all of Mendel’s laws (1865), the
models of quantitative genetics (Fisher 1930),
and the Watson-Crick model of DNA (Watson
and Crick 1953).
The second and third fundamental princi-
ples—fidelity of transmission and new informa-
tion—are about complementary properties. On
the one hand, an information system must be
able to correct errors in order for its informa-
tion to persist (Pierce 2007; Brooker 2008;
Lewin 2008), but, because the environment is
always changing (see the theory of ecology) and
natural selection requires genotypic and pheno-
typic variation (see the theory of evolution), the
information content of the system must also be
able to produce new information. Thus, the
error correction system cannot be perfect. The
actual error rate (i.e., the mutation rate) is
shaped by evolution (Lynch 2008) and is higher
than the theoretical minimum. These princi-
ples derive from the variation and change over
time principles (Table 4, principles 4 and 8).
The fourth and fifth fundamental principles—
mutation and recombination—embody all of the
ways in which new information can be created (Mor-
gan 1911, 1917). In using the term “errors,” I am
including all types of changes to DNA, including
base-pair changes, deletions, insertions, transpo-
sitions, and polyploidy, as well as epigenetic
changes such as DNA methylation. In Bacteria
and Archaea, recombination occurs in a hap-
hazard fashion. The evolution of meiosis in Eu-
karyotes can be seen as a process through which
DNA exchange and recombination became regu-
larized (Wilkins and Holliday 2009). This is again
a manifestation of the change over time principle
(Table 4, principle 8).
The sixth fundamental principle—random
processes—describes one of the major ways that
contingency plays a role in living systems (Table
4, principle 7). Mutations occur randomly. This
is not to say that all mutations are equally likely;
rather, mutations are never goal directed
(Pierce 2007; Brooker 2008; Lewin 2008). The
independent assortment of genes on different
chromosomes is the best example in biology of
a truly random process. If this were not so—if
an allele could favor its transmittal over its ho-
molog—even a very small advantage would
quickly fix that allele in a population. Linked
alleles would also be quickly fixed, while alleles
linked with the disfavored variant would quickly
become much rarer. Thus, the entire meiotic
machinery is geared toward suppressing the
possibility of such skewing of gene segregation.
Although we know of skewing processes (e.g.,
meiotic drive and transposable elements), they
are exceptions rather than the rule.
The seventh and eighth fundamental princi-
ples—robustness and context dependency—
deal with information usage. They encompass
the entire machinery of transcription and trans-
lation, and link to cellular networks (Table 5,
principle 3) and the ontogeny of organisms
(Table 6A, principle 8; Table 6B, principle 6),
as well as to the external interactions described
by both of those theories (Pierce 2007; Brooker
2008; Lewin 2008). These two principles are
complementary. On the one hand, a persistent
information system needs to be robust to errors.
The processes that allow for some mutations
without phenotypic change (e.g., the degener-
acy of the genetic code) enhance the error cor-
rection system. On the other hand, those silent
mutations can act as a hidden pool of variation for
evolution to act upon if they suddenly are no
longer silent.
Such a change in expression is the context
dependency of information usage. That context
includes the other DNA sequences on the same
chromosome, the DNA sequences of other alleles
at that locus, the rest of the genome, and, most
notably, the environment outside the cell. That
environment can include other cells within the
same organism or in other organisms, as well as
September 2010 313TOWARD A CONCEPTUAL FRAMEWORK FOR BIOLOGY

the individual’s physical surroundings. That is,
context dependency includes the concepts of
dominance, epistasis, genotype-environment in-
teractions, and maternal effects. It also includes
cultural and other such forms of non-genetic in-
heritance. Context dependency is a type of emer-
gent property (Table 4, principle 6).
The ninth fundamental principle—evolu-
tion—parallels those of the other theories. Not
only mutation and recombination rates are
shaped by evolution. Phenotypic plasticity—the
ability of the system to respond to environmen-
tal context dependency—is heritable and select-
able (Scheiner 1993). Evolution establishes a
relationship between the quantity of informa-
tion and its usefulness (Frank 2009).
Table 8. The Theory of Ecology
The first fundamental principle—heteroge-
neous distributions—is one of the most striking
features of nature: all species have a heteroge-
neous distribution at some, if not most, spatial
scales. Arguably, the origins of ecology as a dis-
cipline and the first ecological theories can be
traced to its recognition (Forster 1778; von
Humboldt 1808). This heterogeneous distribu-
tion is both caused by and a cause of other
ecological patterns and processes. This is the
ecological manifestation of the variation princi-
ple (Table 4, principle 4).
The second fundamental principle—interac-
tions—includes within it the vast majority of
ecological processes responsible for heteroge-
neity in time and space. They include both in-
traspecific and interspecific interactions such as
competition, predation, and mutualism, as well
as feedbacks between biotic and abiotic compo-
nents. Many definitions of “ecology” are restate-
ments of this principle (Scheiner and Willig
2008). This principle links to the interaction
principle (Table 4, principle 5).
The third fundamental principle—varia-
tion—is the result of processes that derive from
the theory of organisms. It is notable that many
constitutive theories and models within ecology
assume invariance, and, in some cases, relaxing
this assumption has led to substantial changes
in predictions (Scheiner and Willig 2011b). For
example, if the actual chance of survival varies
among individuals within a population, treating
all individuals as identical can substantially
over- or underestimate the risk of local extinc-
tion from demographic stochasticity (Kendall
and Fox 2003). This principle links to both the
variation and interaction principles (Table 4,
principles 4 and 5).
The fourth fundamental principle—contin-
gency—has grown in importance in ecological
theory and now appears in a wide variety of
constituent theories and models. Contingency
is an important cause of the heterogeneous dis-
tribution of organisms (Gleason 1926), both at
very small and very large extents of time and
space (e.g., a seed lands in one spot and not
another; a particular species arises on a par-
ticular continent). This principle links to the
theories of genetics and evolution. It also exem-
plifies the dynamic nature of a theory. The
consensus that contingency was a fundamental
process emerged from a debate among ecolo-
gists during the 1960s through the 1980s. This
principle is the ecological manifestation of the
contingency principle (Table 4, principle 7).
The fifth fundamental principle—environ-
mental heterogeneity—is a consequence of pro-
cesses from the theories of earth and space
sciences, as well as from other biological prin-
ciples when those environmental factors are bi-
otic (Gurevitch et al. 2006). For example, sea-
sonal variation in temperature is the result of
orbital properties of the Earth, whereas a variety
of geophysical processes create heterogeneity in
environmental stressors such as salt (e.g., wave
action near shores) or heavy metals (e.g., geo-
logic processes that create differences in bed-
rocks). This principle contains a broad class of
underlying mechanisms for the heterogeneous
distribution of organisms.
The sixth principle—finite resources—is again
a consequence of processes from the theories of
earth and space sciences as well as other biolog-
ical principles (Gurevitch et al. 2006). Although
variation in resources is similar to variation in
environmental conditions, a fundamental distinc-
tion is the finite, and thus limiting, nature of these
resources. Unlike an environmental condition, a
resource is subject to competition. For exam-
ple, seasonal variation in light and temperature
are caused by the same orbital mechanisms, but
light is subject to competition (e.g., one plant
shades another) whereas temperature is a con-
dition and not subject to competition.
The seventh fundamental principle—birth
and death—is a consequence of the processes
that derive from the theories of cells and organ-
isms. While birth and death come about
through cellular and organismal processes,
their rates depend on the interactions of an
organism with its environment (Hasting, 2011;
Holt 2011). This principle derives from biolo-
gy’s principles 5 and 9 (Table 4).
The eighth principle—evolution—is the re-
sult of processes that derive from the theory of
evolution. The inclusion of evolution within
314 Volume 85THE QUARTERLY REVIEW OF BIOLOGY

ecological thinking was an important outcome
of the Modern Synthesis. Although evolutionary
thinking about ecological processes goes back
at least to Darwin (1859), only since the 1920s
has ecology embraced its principles (Collins
1986; Mitman 1992), and its widespread accep-
tance occurred primarily in the latter half of the
twentieth century.
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