NATURAL GENETIC ENGINEERING AND NATURAL GENOME EDITING

No Genetics without Epigenetics? No Biology

without Systems Biology?
On the Meaning of a Relational Viewpoint
in a Complex Account of Living Systems
Gertrudis Van de Vijver
Centre for Critical Philosophy, Department of Philosophy and Moral Science,
Faculty of Literature and Philosophy, Ghent University, Ghent, Belgium

In this article, we propose to reflect on the meaning of complexity in relation to current

biology, and in particular, in relation to current systems biological developments by
considering them as confronting biology with the idea of a complex part–whole deter-
mination of living systems, that is contextual as well as stratified. We attempt to trace
as clearly as possible the abstract core of the idea of parts and wholes that is at stake
in this contextual determination. In doing so, we have found inspiration in Kant’s view
on living systems. We argue that Kant’s transcendental viewpoint can be relevantly ac-
tualized and extrapolated as a relational account of living systems, and will explore its
ramifications starting from a multilevel view of living systems.

Key words: parts and wholes; contextual determination; multi-level determination;

complexity; relational epistemology; epigenetics; systems biology; Kant

Introduction On the other hand, it requires, if the message of

context is taken seriously, a clarification of the
Developments in epigenetics, epigenomics, status of the parts identified by genetics itself. In
and systems biology have challenged the idea this regard, it can be said that there is no epige-
that living systems can be understood and ex- netics without genetics (or no systems biology
plained on the basis of their basic constituent without biology), that epigenetics presupposes
components alone. They contributed to the genetics, that genetics comes first and epigenet-
awareness that a more complex approach is ics after or beyond it. But in a less trivial, con-
needed, an approach that abandons the idea ceptual sense, it can as well be said that there is
that smaller parts are causally sufficient and no genetics without epigenetics (or no biology
explanatory for the living and that wishes to without systems biology). More boldly, it can
take into account, in addition, a beyond of the be said that there can be no genetics without
parts. This awareness implies, on the one hand, epigenetics, or even that there has never been
the need to understand what precisely goes be- a genetics without an epigenetics. At stake is
yond the parts and in what sense this “beyond” the awareness of the meaningfulness of parts in
constitutes the context or the perspective within function of a context, and this in two ways: on
which the parts can have a place and a meaning. the one hand, a meaning is revealed of parts
within a context, but on the other hand, the
impossibility emerges to have parts without a
Address for correspondence: Gertrudis Van de Vijver, Centre for context.
Critical Philosophy, Department of Philosophy and Moral Science, Fac- Systems biology today is particularly con-
ulty of Literature and Philosophy, Ghent University, Blandijnberg 2,
B-9000 Ghent, Belgium. Voice: +32/496525728; fax: +32/92207305.
fronted with the challenge to account for the
[email protected] complexity of living systems. It starts from the
Natural Genetic Engineering and Natural Genome Editing: Ann. N.Y. Acad. Sci. 1178: 305–317 (2009).
doi: 10.1111/j.1749-6632.2009.05010.x  c 2009 New York Academy of Sciences.

305
306 Annals of the New York Academy of Sciences

observation that there is an overwhelming mass a consequence of this choice, the basic research
of data about the building blocks of living or- agenda is set out in terms of a questioning of
ganisms, and acknowledges the need to articu- the possibility of a complex relation between
late an integrated view on biological processes parts and wholes: how is it possible that a whole
in which these data, concerning the role of determines the parts, while the parts in a cer-
genes, proteins, cells, and even the environ- tain sense also determine the whole? It is our
ment, can have a place and a meaning. Hence, conviction that the meaning of current systems
it has to account for the integration, organiza- biology and the orientation it takes largely de-
tion, context, or perspective within which cer- pend on the treatment it proposes of this rela-
tain parts can have a place and a meaning. In tion. We argue, in line with Kant, that a proper
our view, to address the complexity of the living treatment of this complex part–whole relation
requires an articulation of the specific contexts requires special attention to objectivity.
that formally transcend the isolated data and In this article, we deal with the status of cur-
that allow us to understand the latter in an in- rent systems biology—what is it and what can
tegrated and systematic way.a it be?—and discuss the ambiguity that can to-
The focus on context, understood as formal day be noted in relation to it. In order to frame
organization, is not an evident choice, as it is this ambiguity, we propose to return to Kant’s
a widespread idea that a unified understand- treatment of living systems and its implications
ing of life requires: (1) a view on its compo- for objectivity and take this as a main source of
nent parts, the cells, (2) a view on the life cycles inspiration to deal abstractly with the problem
of all cells—their formation, growth, develop- of complexity, by considering it from the angle
ment, and reproduction—as based in chemical of objectivity, and more precisely by seeing it
reactions among similar sorts of molecules, (3) as instantiating a genuine problem of objectifi-
a view on the way in which amino acids are cation. Finally, we argue that a relational view-
put together to form proteins, as specified by point is epistemologically speaking most appro-
DNA and RNA according to a nearly univer- priate to deal with the complexity encountered
sal and precise scheme.1 Our research puts the in living systems.
investigation of the formal principles that are
specific to biological organization on top of this
list and gives it priority over the other items.b As Systems Biology: What It Is
and What It Can Bec

a
The sequencing of the human genome is one
This research is part of an interdisciplinary research project called
“Complexity thinking in a post-genomic era: a science-philosophical study of the most notorious examples of the impres-
of systems biology and its implications for (i) molecular biology, (ii) phi- sive mathematical and computational means
losophy of biology, (iii) sustainable agriculture, and (iv) image building
and perception with regard to (transgenic) organisms in various media,” developed to sequence the genomes of living
based at Ghent University since 2005. Four research groups are involved, systems. During the past decades, huge ex-
representing the four relevant disciplines: philosophy, molecular biology,
agricultural sciences, and communication sciences. The philosophical re-
pectations arose around these sequencing ca-
search unit (Centre for Critical Philosophy) is the coordinating instance. pacities. At some point, it was thought that
The purpose of this project is to investigate the potential of current systems
biology to address the living organism as a complex system. This project
the production of genetic, structural, data, for
follows naturally on previous research on epigenesis and epigenetics, as it example, the identification of unique, mate-
abstractly deals with the same problem, namely the one about the com- rial, molecular components, would in and of
plex interrelatedness of parts into an integrated whole. Our research on
epigenetics led to the organization of an international symposium held at itself lead to a sufficient understanding and
the University of Ghent in 2001, titled “Contextualizing the Genome: the
Role of Epigenetics in Genetics, Development and Evolution.”15
b
This aspect was stressed by various authors, for instance by Maturana
c
and Varela, who considered that an adequate treatment of life requires a The presentation and interpretation of current systems biology finds
treatment of its organizational and self-organizational nature. As will be its basis in a cooperation with Joris Van Poucke. We draw among others
shown, this was also the choice made by Immanuel Kant. on Ref. 16, 17.
Van de Vijver: Complexity and Relational Thinking 307

explanation of the functional processes char- However, difficulties and limitations of this
acteristic of living systems. At the heart of it approach became more and more apparent
lies a conflation between function and struc- over the years. The study of epigenetic phe-
ture, captured through the modern gene con- nomena, complexity issues, processes regulat-
cept, and more specifically, through the gene ing in various ways the expression of so-called
reductionism of molecular biology. At least two information contained in the genetic data ques-
different modes of reductionism are at work in tioned the linear causal view expressed in the
this regard that return in current systems biol- central dogma. It became clear that even the
ogy. The first is the one undertaken by Mendel, most complete sequencing, even the vastest pro-
who broke an organism apart in terms of phe- duction of structural data would be insufficient
notypic traits (characters), which were in turn to attain the goal of unravelling the functional
reduced to the working of factors. The second secrets of life. What became the fundamental
form of reductionism subscribes to the possibil- question was the idea of function being re-
ity of breaking down the biological organism ducible to a set of material components, that is,
to its basic material constituents, its molecules. the idea of function conflating with purely ma-
These two modes of reductionism eventually terially (molecularly) identified parts. Instead of
converged in the modern gene concept, which considering genetic data as a basis in itself dic-
implied the identification of a Mendelian factor tating, instructing, or sufficiently informing the
with a special molecule, the gene.d The com- functioning of living systems, it appeared that
bination of the two gave rise, not just to all the functionality of genes had to be understood
the molecules of the system (this would be only on the basis of more encompassing organiza-
a material reductionism), neither just to func- tional contexts that are in a certain sense in-
tional entities (which would consist of only a dependent from the underlying material parts.
part–whole reductionism) but to a piece of mat- The exploration of this idea led to the analysis
ter which contains an inherent encoding—the of the regulative workings of more or less prox-
sequence of the base pairs of the molecule— imate, organizational layers, and hence to the
of the whole functional organism. A detailed development of the disciplines nowadays iden-
knowledge of the encoding pieces would then tified as the “omic” sciences.2 Until this day,
allow us to know the whole system as a liv- these “omic” sciences have contributed to the
ing, functional entity. This is the ideal pursued proliferation of still more data, beyond those re-
by the genome projects, and it can explain the lated to the sequencing at the genetic level. It re-
hope that arose around the idea of sequencing, mains largely unclear, however, how or whether
in particular in relation to the human genome. this renewed data production will contribute to
The idea of a genetic blueprint, originating in genuinely address the aforementioned difficul-
evolutionary processes guided by blind varia- ties. One might conjecture that an “extended
tion and natural selection, captures exactly this central dogma” is at work, leaving the idea of
expectation. a linear viewpoint on causal determination ba-
sically unquestioned, but extending it from ge-
d
Lenny Moss (2003) comes to a similar conclusion when he makes the
netic structural data to the structural data of
Gene-P/Gene-D distinction, even if his historical analysis goes further the “omic” sciences.
back in time and is centered around the preformationism and epigenesis Today, current systems biology starts from
debate. He states: “The preformationist gene (Gene-P) predicts pheno-
types but only on an instrumental basis where immediate medical and/or the overwhelming mass of data about the build-
economic benefits can be had. The gene of epigenesis (Gene-D), by con- ing blocks of living organisms and about the
trast, is a developmental resource that provides possible templates for RNA
and protein synthesis but has in itself no determinate relationship to or- regulative networks in which they are embed-
ganismal phenotypes. The seemingly prevalent idea that genes constitute ded. It wishes to overcome the relative fail-
information for traits (and blueprints for organisms) is based, I argue, on
an unwarranted conflation of these two meanings which is, in effect, held
ures of the genome projects, acknowledging
together by rhetorical glue” (p. iv).18 that “biological systems are far too complex to
308 Annals of the New York Academy of Sciences

be solved by classical biological approaches.”3 ing of what “governs” life. Cross-discipline and
Structural data, concerning the materiality of large-scale biological research is the present-
genes, proteins, cells and even the environment, day answer to complexity. To that end, exper-
are seen as important, but a complex account of tise from different domains—physics, mathe-
the living requires an integration of these data, a matics, and engineering—is combined, leading
more encompassing context within which they systems biology to look for predictive mathe-
can have a place and a meaning. Systems biol- matical models “that integrate all relevant data
ogy therefore focuses on the relations between on the topic of investigation,”3 as well as for
data, on their system’s aspect, more than on instruments that will help to “focus, synergize,
the data themselves. It is on this basis that manage and fund” research. In sum, the very
it proposes to generate an understanding on heart of systems biology is constituted in terms
“how their maze of interactions in time and of an iterative cycle of model-driven experi-
space govern life,”3 to genuinely “turn data mentation and experimental data-driven mod-
into knowledge,” or else, to “bring genomes elling, combined with novel systems analysis
to life.”4,12–14 tools. Given the extremely complex behavior
It is obvious then that a complex account of multilevel networks of interactions, “intu-
of living systems, one that goes beyond “classi- itive approaches” are considered “ineffective,”
cal biological approaches,” requires a clear ac- and the hope is on the contrary that quantita-
count of parts and wholes. From a philosophical tive and predictive mathematical modelling will
point of view, it is tempting to take the idea of somehow be helpful to the biologist in making
wholes being more than the sum of the parts decisions about what experiments are the most
from the side of ideality: if systems biology can informative.3
no longer be satisfied with a material identifi- That systems biology links the challenge of
cation of parts, then it will have to address the complexity in the first place to finding an ad-
way in which parts are parts in function of a equate computable integration of a plurality
more encompassing whole, and that whole can of perspectives becomes particularly clear in
only be conceived of as an ideal moment, in the the distinction between bottom-up approaches
sense that it is not to be equated to the mate- and top-down approaches. It is said that these
rial identification of parts. If wholes are more approaches differ mainly “with respect to the
than the sum of the parts, then the challenge emphasis placed on the molecular details and
is to understand what it is that is beyond the the quantification of the dynamic behavior
materiality of parts, what it means to say that of the interactions between the components
wholes are formal or ideal, and in what sense of the system” (my emphasis).5 The bottom-
the whole determines the parts as parts of a up approach seeks biological meaningfulness
certain kind. In its most general presentation, by giving priority to local functional data. It at-
systems biology can be taken to subscribe to tempts to turn the structural data of the “omic”
the ideal of wholes being in some sense more sciences into something biologically meaning-
than the sum of the parts. However, this ideal ful by using these as resources to extend tra-
stance is, to our knowledge, rarely explored in ditional pathway modelling in molecular bi-
any explicit sense. Or more precisely, the poten- ology, resulting in an ever growing network.
tial it has in constituting the materialist basis as It encounters the challenge of complexity in
a material basis of some sort, is rarely acknowl- as far as it seeks to “reconstitute a model of
edged. Instead, the agenda of systems biology a whole biological system by combining the
subscribes basically to a pragmatically inspired, pieces of information it generates.” Even if it
utilitarian, program of computation that fo- subscribes to the idea that the complexity of
cuses on combined efforts of calculation that as the living has to be and will be approached
such should eventually lead to an understand- “from below,” from the parts, it sees this as
Van de Vijver: Complexity and Relational Thinking 309

a matter of gradualness and acknowledges In this way, it “assigns biological functions to

the need to find relevant modules that can ex- the genome of an organism” (my emphasis).8
plain a certain level of autonomy characteris- Quite understandably, the challenge is to come
tic of groupings of parts. In that regard, the to a “clear concept of wholeness” and to ad-
bottom-up approach struggles to find adequate dress “the ontological question of how to define
criteria for the demarcation of these modules wholeness.”6 However, even if there is more
“to guarantee a certain level of autonomy” (my concern for the “biological reality” than was
emphasis).8 Empirical, textbook-driven decom- the case in the times of cybernetics or system’s
position is what guides the assessment of the theory, mainly because of the fact that more
regulative impact of large-scale networks, leav- “biological” data are available nowadays, the
ing the question of the relation between struc- problem of the top-down approach is still to
tural data and functionality largely implicit, recover biologically embedded functional or-
and starting from a functionality that is inter- ganization starting from the global level. In this
nal and embedded to local empirical contexts regard, the underlying hope is that the modules
in which subsystems are performing particu- or units identified in the bottom-up approach
lar physiological functions. Hence, the bottom- will eventually converge with the modules iden-
up approach is operating in the middle of a tified top-down, or that experimental research
given biological functionality, without making will converge with the computational analyses
explicit what functionality or wholeness consists of structural data. Thus, systems biology, in tak-
in, without “transcending” the level of biologi- ing up the challenge of complexity, attempts to
cal functioning and its close modelling.e “bridge the gap” between the two: if there is suf-
In contrast, the top-down approach is basi- ficient knowledge from below, then the bottom-
cally linked to a high-throughput reductionism up approach is to be preferred. If this is not the
but focuses on the interpretation of the struc- case, then a top-down account will be needed
tural data on the basis of global system-models. as a supplement.g
It considers that the system’s nature of living Considering the quite straightforward focus
beings has implications from the very start, in on computability and the utilitarian embed-
that the whole is seen to have a major impact ding of its research, what can it mean then that
on the workings of the levels below. The roots systems biology will “bring genomes to life,” or
of the top-down approach are biological cy- “turn data into knowledge”? Its factual agenda
bernetics and systems theory, and its focus is appears to still be largely determined by the du-
primarily on the regularities at the global level. alistic, either/or space from within which the
In this, the role of the “omic” sciences is more difficulties mentioned earlier emerged, and in
substantial than in the bottom-up approach. relation to which a unification is pursued. In-
The data are considered as global data span- deed, it either looks top-down for a substantifi-
ning over the whole system at a certain time cation of wholeness that will allow for an ad-
point. The top-down modelling approach starts equate understanding of the parts, or it sticks
its analyses from these global, structural data to the parts and attempts to generate and un-
and tries to make them functionally meaning- derstand organized wholes on that basis, and
ful by an engineering analogy in terms of de- then it hopes that both approaches will at some
sign principles, such as modularity, control con-
cepts, redundancy, complex engineering, etc.f

g
e
Krohs & Callebaut suggest something along these lines when stating “If the knowns outweigh the unknowns, then the bottom-up approach
that structural data are generated without theory and are very poor in can be taken with confidence. But in the case where there is a large number
generating theory.6 of unknowns, the top-down approach is the logical way to bridge the gap
f
It is evident that we don’t imply here the engineering perspective as between the knowns and the unknowns.”5 One can wonder, however, why
related to “natural genetic engineering.” it should be per se the top-down that functions as a supplement.
310 Annals of the New York Academy of Sciences

point converge.h How to combine this factual lation and then considered as building blocks
situation with its general ambition, that con- for a more encompassing whole, the issue of
sists in “bringing genomes to life,” which seems functionality is narrowed down according to
to imply rather a neither/nor space: neither to principles that are perhaps pragmatically justi-
subscribe to an atomistic materialism, nor to fied, but that are hardly relevant to deal with
a mystical holism; neither the parts alone, nor what is called a living system. Rosen, inspired
the whole alone are sufficient to account the by Rashevsky, was bold on this very point: if
organism as a functional entity. you don’t give up the idea of an identifiable,
The basic problem is, in our view, that intrinsically nonfunctional material basis, not
notwithstanding its overt discourse on complex- only will you not be able to recover organiza-
ity and on the ambition to go beyond classical tion (system, complexity) afterwards, you will
biological methods, the metaphysics and epis- have lost it in an irretrievable way. In other
temology at work in current systems biology words, not only is it required to acknowledge
are still very much in line with the “classical” the intrinsic limitations of an approach of life
view on the identification of parts and wholes. in terms of a simple aggregation of individual
It seems to us unlikely that as long as parts and parts, it is also required to acknowledge the
wholes are seen as terms that can be defined need for a principle, that is, an ideal supple-
independently of each other and that need to ment that captures and expresses the idea that
be unified afterwards, systems biology will suc- the system is complex.i To further articulate
ceed in addressing the complex system-nature this idea, we now turn to Kant’s viewpoint on
of the living. Instead, what can be noted is that living systems. To us, he is the philosopher par
its research is inscribed into an ever more press- excellence to have stressed, firstly, that the ob-
ing search for effective integrated calculability. jectivity of the sciences is a matter of very specif-
And it can only pursue this research in terms ically organized subjective conditionality, that
of a computable integration or a unification of is, a matter of organized ideality. And secondly,
bottom-up and top-down approaches.7 Mean- that living systems, by resisting the objectify-
while, systems biology can no longer accept the ing procedures that are proposed in relation to
idea that function and structure can be con- dead systems, reveal the decisive status of this
flated. The struggle current systems biology en- subjective conditionality in relation objectivity,
counters reveals the untenability of such a con- that is, they reveal that objectivity is a matter of
flation. However, it does not seem to take note organized ideality in view of certain interests
of the meaning of this untenability. We conjec- and purposes.
ture that this is the case to the extent that it
escapes the complex issue of parts and wholes,
which means that it escapes the complex rela- Kant on Living Systems
tion between structure and function. As long as
the parts are not conceived of “in relation” to What does it mean that Kant is the philoso-
a whole, as long as parts are identified in iso- pher par excellence of objectivity? His fa-
mous question “How is universal and nec-
essary, objective knowledge possible?” (“How
h
Our analysis is close to the one of Webster and Goodwin of almost are synthetic a priori judgments possible?”) is
thirty years ago, who spoke of an unhappy marriage between holism and
atomism: “contemporary biology relies upon an unhappy marriage be-
tween atomism and a materialistic (and often mystical) holism in which a
i
predominantly atomistic and functionalist conception of the organism per For Rosen, this means that reference needs to be made to something
se is coupled with a holistic conception of a ‘central directing agency’ con- like an organization, which is to him a formal or abstract concept that
ceived as a material entity—the so-called ‘genetic programme”—which is indicates an arbitrariness in the relation between the whole and the com-
supposed to determine, order, and unify the atomic units and events. The ponents: nothing in the components mandates a particular organization,
organism as a real entity, existing in its own right, has virtually no place in and nothing in the organization mandates particular components. To
contemporary biological theory” (p. 6).19 Rosen, structure, or matter, are “closed” concepts.20
Van de Vijver: Complexity and Relational Thinking 311

addressed through an analysis of the conditions to objectively know living systems on the basis
within which something like an object can ap- of universal concepts. The main reason for this
pear. In other words, he focuses on the space is that their organization is internally driven—
within which things can be domesticated by there is an intrinsic interrelatedness of parts and
a universal observer so as to lead to objective wholes—and is triggered by contingent sensi-
knowledge, for example, to something that is tive encounters resulting, among other things,
intersubjectively sharable and communicable. in feelings of pain and pleasure. The latter in-
In his first critique, The Critique of Pure Reason, stall limits for the living system and inscribe
one might get the impression that a logic of it into a contingently based, local, and histor-
discharge is at work: in as far as the knowing ical context. To Kant, there is principally no
subject succeeds in producing objective knowl- universal rule that can dictate the lawfulness of
edge, it succeeds in constituting an object of this contingency: living systems are not chaotic,
universality and necessity, and hence, the sub- the rule is not that “anything goes,” but there
ject appears itself as a universal subject ulti- is no universal, external rule or recipe either
mately disconnected from the object.8 This im- on the basis of which a living system could be
pression is no longer tenable in reading Kant’s constructed and known on an a priori basis. To
third critique, The Critique of Judgment, where liv- accept in this regard an a priori universal con-
ing systems are seen as essentially problematic cept, would only undermine the assumed in-
in relation to the procedures of objectification terrelatedness of parts and wholes by realizing
proposed in the first critique.9 To Kant, the a determinable synthesis of their phenomenal
case of impossible objectification that is instan- variety under a concept. Kant argues against
tiated with living beings, reveals the nondetach- this: a system is living precisely to the extent that
able workings of subjective conditionality. It is its specific internal interrelatedness excludes a
this idea of impossible objectification, related universal determination through concepts. The
to the absolute need to take into account the possibility of the living is captured in a purely
meaningful engagement of a knowing instance, negative fashion: its identity is only identifiable
that we connect to the message of complexity, through what it is “not”; is living that which is
and hence to the challenge that can be read not objectifiable.
in relation to what currently happens in sys- There is, however, an answer to this impossi-
tems biology or epigenetics. Let us explain first bility. It is indeed possible to connect to liv-
how Kant comes to his insight on impossible ing systems, on the basis of an assumption,
objectification. an “as if,” called by Philonenko a “supple-
In the second part of his third critique, Kant ment of meaning,” that holds that living sys-
argues that we have to assume that living be- tems are natural purposes that cannot, and will
ings are natural purposes, that is, organized not, be objectified. The “as if” simultaneously
and self-organizing structures in which nothing captures an impossibility, the one of objectively
is for nothing, in which every part is a func- knowing living systems, and a possibility, the
tion of the whole, and in which the whole is a one of grasping and connecting to the living
function of every part.j To him, it is impossible

impossible to conceive of an organism by assuming that no purpose at

all is at work; (2) “This second requirement is that the parts of the thing
j combine into the unity of a whole because they are reciprocally cause and
Kant describes the natural purposes in the Analytic of Teleological Judg-
ment, more in particular in §64 and § 65, titled respectively “On the Char- effect of their form” (p. 252).9 On the basis of this second requirement,
acter Peculiar to Things Considered as Natural Purposes” and “Things Kant proposes to make a difference between a work of art and a natural
Considered as Natural Purposes Are Organized Beings.” Kant states: “a purpose. Because indeed, specific to natural purposes is the organization
thing exists as a natural purpose if it is both cause and effect of itself ” between the parts, a production of the parts among each other, “the parts
(p. 249).9 He then adds two requirements: (1) “First, the possibility of are there for the sake of the others and for the whole,” and it is that which
its parts (as concerns both their existence and their form) must depend provides the natural purpose with “a systematic unity in the form and the
on their relation to the whole” (p. 252)9 , by which he means that it is combination of all the manifold contained in the given matter” (p. 252).9
312 Annals of the New York Academy of Sciences

dynamics by somehow carrying the assump- practices of a living subject. In as far as some-
tion of their intrinsic purposiveness.10,k In more thing is safely “externalized” in this sense, it can
general terms: the subject accedes to a possibil- become reproducible and genuinely objective.
ity through the acknowledgement of a radical Therefore, what the third critique enables us
impossibility. Or still in other words: the fail- to see is that objectivity requires specific efforts
ure of objectification installs subjectivity in the of externalization, and that it is on the basis
form of a supplement. of these efforts that a distinction can emerge
We believe that this idea, of “impossible pos- between subjectivity and objectivity, between
sibility,” allows us to coherently understand the what is inside and what is outside.
challenge of objectivity (and subjectivity) that It is through the encounter with natural pur-
Kant gradually explored through his three cri- poses that this side of objectivity can become
tiques, and of which the third critique, as Kant more explicit. Because indeed, natural pur-
himself admits, is the moment of unification poses express the idea that an orientation in a
and completion. The basic thing that Kant’s phenomenal world is somehow to be obtained
third critique shows is that the security or relia- from within the active engagement of a living
bility of objective knowledge is not to be envis- system, in the radical absence of an absolutely
aged in terms of a correspondence or a com- valid a priori external rule. If they are not know-
parison with something situated outside of it, a able objectively, if it is impossible to determine
preexisting outer world, or an absolute point of them on the basis of an external rule, it is be-
reference of some sort. On the contrary, what cause of their internal organization. They show
is involved in the quest for objective knowledge themselves as principally resistant to any objec-
is a particular kind of orientation in a phenom- tification, and as such they reveal the impossi-
enal world, and more specifically, a particu- bility to objectify in terms of “pushing outside”
lar kind of distinction between inside and out- something of the internal, privately based dy-
side. If, in the first critique, objective knowledge namics. Clearly then, subjectivity and objectiv-
shows itself as reproducible and stable, it is not ity are not to be conceived as two ontic spheres,
because it is in some sense adequate to an object they are two spheres of conditionality that ap-
“out there.” As the third (but also the first) cri- pear as co-constitutive within the range of the
tique can show, there is objectivity to the extent active engagement of a knowing, living, subject,
that an object is constituted, in a very specific that is, within the range of the questions asked
way, from within a subjective conditionality: by the knowing subject. In fact, Kant’s “Coper-
an object is that which has been successfully nican revolution” points precisely to this: as
“pushed outside” of the sphere of the contin- things don’t dictate the way in which they are
gently based individual, and largely implicit, to be apprehended, what can be revealed about
them is what is allowed within the range of the
question, and this is as revealing about the ques-
k
Developments in cybernetics, with the distinction between first and
second cybernetics, can illustrate this quite well. See Ref. 21. Kant ex-
tion as it is about the answer. The constraint,
plicitly points at this “impossible possibility” in his Analytic of teleological the contingent perspective of the “questioner,”
judgment. On the one hand, it is because the thing itself is a purpose
that we have to think it under a concept or an idea, determining in an a
is the possibility.
priori way everything that is to be understood in the thing. And on the
other hand, it is necessary to suppose that there is in the natural purpose
an internal organization that provides it with a unity, otherwise the idea
of the whole couldn’t determine it, even if it is only as a principle of Complexity: Exploring the
knowledge, serving the one who judges. Kant is explicit about this in the Resistance to Objectivity
sentences immediately following the second requirement: “For only in this
way is it possible that the idea of the whole should conversely (reciprocally)
determine the form and combination of all the parts, not as cause—for We believe that the Kantian epistemologi-
then the whole would be a product of art—but as the basis on which
someone judging this whole cognizes the systematic unity in the form and
cal viewpoint is relevant to understand what
combination of all the manifold contained in the given matter (p. 252).9 happens in the debates around complexity,
Van de Vijver: Complexity and Relational Thinking 313

self-organization, chaos, purposiveness, and partners (parts and wholes, objectivity, and sub-
emergence. These debates time and again jectivity) to be integrated afterwards. In other
emerged during the past decades and often had words, it needs to find a concept of wholeness
the living system as a point of focus. Moreover, that goes hand in hand with a concept of parts.
they frequently functioned as a symptom, in- Or still, it has to find a nonoppositional, non-
dicating that something resisted the expected, dualistic way of dealing with parts and wholes.
usual, standard (i.e., predictive, law-like) scien- Secondly, it implies an account of function and
tific procedures.l The answers to this “irrup- structure that makes explicit the meaning and
tion” of complexity were basically of two kinds: the possible relations between internalist views
they would either be in favor, often leading to and externalist design or engineering views on
a plea for vagueness, subjectivity, relativity— function. And finally, in a more general sense, it
we can call these the subjectivistic answers— requires an adequate theory of objectivity that
or they would be vehemently or frenetically avoids the opposition between the objective-
against the message of complexity understood real and the subjective-metaphorical. There-
in subjectivist terms. The latter often implied fore, in our view, a strong message of complexity
an ideological discourse about the possibility requires the transcending of such oppositions,
to obtain objective knowledge in the future, which means that it (1) gives priority to context,
with enough time and money, and as such en- (2) shifts towards conditionality, and (3) tarries
dorsed the possibility of finding a universal rule with the negative.
for the complexity of the living—we can call
these the objectivistic answers. Our hypothesis Complexity Involves Priority of Context
now is that the failure to measure up the liv-
ing to the standards of objectification has been To address the living system as a complex
taken too frequently from an objectivistic angle, entity is to attempt to understand it from the
leading to a simple postponement of attempts perspective of the specific contexts that make
to treat the living in objective terms, and mean- it possible and that formally transcend the iso-
while confining it to the domain of the subjec- lated data and allow an understanding in an in-
tive, the relative, and the metaphorical. As a tegrated and systematic way. There is, in other
consequence, the truly important question of words, a priority of the formal principles spe-
the co-constitutive relation between objectivity cific to biological organization, and this priority
and subjectivity, as well as the very conditional means nothing more, but also nothing less, than
nature of objectivity, has been evaded. A criti- that the focus is not on the material content
cal, transcendental account can be relevant in (the parts) but on the conditions that constrain
this regard, not only because objectivity and material content. To look for smaller parts in
subjectivity are seen as co-constitutive, but also relation to living systems inevitably means to
because it addresses the question of the em- close them.m The idea is to first focus on or-
beddedness of objectivity and subjectivity from ganization, to throw away the idea of objec-
within the living dynamics. In what follows, the tified and separable parts from which to start
basic tenets of such a critical account on com-
plexity are spelled out.
m
If complexity thinking purports to transcend Bourg and Papaux are in our view correct in speaking about a “meta-
physics of genetically modified organisms (GMOs)” that is at work in the
the oppositions just sketched, this means, firstly, philosophical and the (quite emotional) public debate about them. For
that it needs to go beyond the either/or op- one side, GMOs are dangerous, and research should not be pursued, for
the other side, GMOs are not dangerous at all, and research ought to
position between two independently identified be pursued and supported at all costs. The metaphysics at work is one
that is oppositional, either/or, and that can be characterized as either
subjectivist (don’t pursue research) or objectivist (do pursue research, un-
l
This is basically what Robert Rosen explained in relation to derstood in terms of purely computational rationality and cost/benefit
Schrödinger’s “What is life”? For a discussion, see Ref. 17. utilitarianism).22
314 Annals of the New York Academy of Sciences

in a relevant way, and just stick to the organi- in-between is actively entertained, and this can
zation. As mentioned earlier, if you don’t give only happen by suspending the substantifica-
up the idea of an identifiable, intrinsically non- tion of either parts or wholes conceived of
functional material basis, not only will you not independently of each other. This implies an
be able to recover organization afterwards, you entertaining of the conditional tension from
will have lost it in an irretrievable way. There is within which objectivity and subjectivity, parts
no further justification for this choice of priority and wholes, are being constituted. Epistemo-
then the contingent “factum” of life: “there is logically speaking, this amounts to an active
life.” bearing of the conditionality, or in other words,
to the acknowledgement of an engaged, ever
Complexity Shifts its Awareness to questionable, participation in the constitution
Conditionality of objectivity as well as subjectivity.10

Complexity requires an analysis of the condi-

Complexity Involves Tarrying
tions of possibility of the relationship between
with the Negative
parts and wholes. The shift from opposition-
ality to conditionality expresses the idea that Life is a matter of conditionality, of suspen-
the complexity of an organism can only be un- sion, of entertained tension in between a ma-
derstood in terms of its dependency on con- teriality of parts and an ideality of wholeness.
text: what there is depends on how it is carried This is precisely what the idea of a formal or-
through a context.n As oppositions are depen- ganization captures: life is not in the parts, it is
dent on context, then an appropriate question not in the whole, it is beyond or in-between, it is
is: how are these oppositions possible? What it neither/nor, and not either/or. Any form of
the meaning of the terms that are seen as oppo- conflation of parts and wholes (as in classical
sitional? The idea here is to take into account gene-reductionism) implies an elimination of
not just the beyond (epi), but also the perspec- this suspensive organization, and hence a re-
tive out of which something can be considered duction of life to dead matter. At first sight,
as a beyond. To address the idea of “no genet- the basic message of systems biology seems
ics without epigenetics” (or “no biology with- to be “neither gene-reductionism, nor mysti-
out systems biology”) is to address the issue of cal holism.” But, as we have argued, it is un-
how distinctions are constituted, or more pre- clear how it will succeed in accounting for the
cisely, how distinctions are being co-constituted complexity of the living organism, as long as it
from within living dynamics. To go beyond a works along the lines of an “either/or,” between
dualism (as well as a conflation) between op- which it looks for convergence. One might ask
posite viewpoints, to avoid the unhappy mar- then: “how to entertain the in-between, how
riage between materialistic reductionism and to tarry with the negative”? The tricky thing
mystifying holism, complexity requires that the about this is that there is no universal rule
to deal with these questions, and there can,
and should be, no such universal rule. But this
n
As Husserl has demonstrated, it is only through the contingent fact doesn’t mean that there is no firmness or artic-
of objective knowledge that subjectivity can be seen to have a particular ulation in denying the substantification at one
constitutive status in relation to objectivity. It is the space constituted by
objective knowledge that retroactively installs subjectivity as a problem, of both sides. The idea of in-between, in our
and not the other way around. On the other hand, it is with regard view, opens up the idea of dynamical structure,
to the potential failure of objectification that subjectivity has a particular
function, the one namely of revealing, from within the context of a possible, from within which opposites can be constituted
contingently given objectification, the meaning of objectivity in its relation as opposites of a certain kind. It opens up for a
to subjectivity. This was already made clear in Descartes’ articulation of
the thinking subject. Without the availability of objective knowledge, there
“supplement of meaning,” as Philonenko calls
would have been no need to come to an explicit account of the subject.23 it, on the basis of which an exploration of the
Van de Vijver: Complexity and Relational Thinking 315

idea of subjective engagement can become pos- how we made a plea for an active entertaining
sible at various organizational layers. This is of the “in-between,” through the active nega-
not a new form of subjectivism, it is a form of tion of the possibility of a substantification of
stratified dynamic structuralism that calls for one of the opposites. If there is complexity, then
an articulation of forms of engaged participa- there can be no objective foundation in either
tion. Because indeed, the following questions the parts or the whole. Instead of looking for
become particularly pregnant: (1) What is pre- an independently defined, solid material basis
cisely a determinative context or organization that could explain the functionality of the liv-
and how to understand its formal nature? (2) ing system (reductionism), instead of looking
How to explain that organization transcends for functionality at a top level and to consider
the locality of the data while having a deter- the material identification of the living as be-
minative impact on their meaning? (3) What longing to another domain (holism), the idea
are the epistemological and ontological impli- is to explore and to explicitly entertain the “in-
cations of a multilevel and relational viewpoint between” of these two options. This involves the
on causality? and (4) At what point, at what acknowledgment of a neither/nor conditional-
level, in what sense, is the observer to be seen ity within which living systems are operating.
as actively participating? Moreover, it considers the interactive dynam-
ics as the starting point on the basis of which all
fixity (including objective knowledge) is to be
Conclusion: A Relational negotiated. Seen from this angle, what a thing
Epistemology is, what a part is, and what a whole is, what
is subjective and what is objective, become the
We started from the idea that systems bi- fundamental question, and asks for an articu-
ology wishes to take up the challenge of ad- lation of the conditionality related to possible
dressing the living system in its complexity. We choices and interests of the related parties. This
have viewed the complexity of living systems is, in our view, the essence of a relational episte-
in terms of an intrinsic impossibility to objec- mology that demands to be articulated at var-
tify, and have argued for the need to articulate ious organizational layers. In this regard, it is
the subjective supplement that expresses the doubtful whether a universal knowing instance,
engaged connection in relation to the living. a transcendental subject, as Kant would have
This “impossible possibility” is of the essence it, is still the most appropriate way of viewing
in living systems, in as far as they are seen as things nowadays. But this does not mean that
incompatible with an a priori universal rule or a critical discussion of the active engagement
concept, in as far as it would be against their through which a sedimentation into objective
self-organizational nature to develop or apply and subjective, at various organizational layers,
such a concept to grasp their nature. In be- is thereby irrelevant or impossible.
ing genuinely self-organizational, they cannot As we have seen, systems biology (as epi-
allow for such a universal rule. genetics did) thus far reveals the need for an
Through the many discussions on complex- alternative viewpoint, as it points to the im-
ity, it can become clear that the difficulty, or possibility of either a purely reductionist or a
the impossibility, to find a universal rule for purely holist viewpoint. But it seems to hesitate
living systems, has lead, most of the time, to to genuinely address the question of active en-
passionate, ideological stances: either in favor, gagement, it refrains from taking up the prob-
or against the attempts to find a universal rule. lematic issue of active constitution of objectiv-
Our intuition here was to reflect beyond this ity, and apparently hesitates to pay the price
either/or oppositionality. That is how we came of engagement itself. There is a price to pay
to the issue of context and conditionality, and anyhow, namely the price of the activity proper
316 Annals of the New York Academy of Sciences

to the engagement. That is what life shows: 4. Kitano, H. 2001. Systems biology: Towards system-
without active engagement, without “supple- level understanding of biological systems. In: Foun-
ment of meaning” there is no connection to dations of Systems Biology. H. Kitano, Ed.: 1–38. MIT
Press. Cambridge, MA.
life, no life at all; the constraint is indeed the 5. Reuss, M. 2007. Marrying diverse partners—a
possibility. Should it come as a surprise then mixed complementarity approach for integrating
that it is precisely in the domain of biology that bottom-up and top-down methods in systems bio-
this issue, time and again, comes to the fore- logy. In Systems Biology: A Grand Challenge for Europe.
front? “What do you want science for”? is a European Science Foundation. Retrieved October
25, 2008, from www.esf.org/research-areas/medical-
question of which Evelyn Fox Keller stressed
sciences/publications.html.
the particular relevance in relation to the com- 6. Krohs, U. & W. Callebaut. 2007. Data without mod-
plexity of living beings.11 It is our conviction els merging with models without data. In Systems
that the insistence of the message of complex- Biology: Philosophical Foundations. F.C. Boogerd, F.J.
ity, is the insistence of this question, which is Bruggeman, J.-H.S. Hofmeyr & H.V. Westerhoff,
a question about an active engagement that Eds.: 181–214. Elsevier. Amsterdam.
7. O’Malley, M. & J. Dupré. 2005. Fundamental issues
asks to be accounted for at various layers, from in systems biology. Bioessays 27: 1270–1276.
a metaphysical as well as from an epistemo- 8. Kant, I. 1997 [1787]. Critique of Pure Reason. P. Guyer
logical viewpoint. Failing to address it through & A.W. Wood (Trans.). Cambridge University Press.
variant forms of objectivism and subjectivism, Cambridge.
or narrowing it down too quickly to a purely 9. Kant, I. 1987 [1790]. Critique of Judgment. W.S. Pluhar
(Trans.). Hackett Publishing Company. Indianapolis
ideological or political issue, is to miss, in our
and Cambridge.
view, the essence of complexity. 10. Philonenko, A. 1984. Introduction à la Critique de
la Faculté de Juger. In Critique de la Faculté de Juger.
A. Philonenko (Trans.) and I. Kant, Ed.: 7–16. Vrin.
Acknowledgments Paris.
11. Keller, E.F. 1996. Just a phrase they’re going through.
We wish to thank the members of the Cen- Interview in The Times Higher Education Suplement, Feb.
tre for Critical Philosophy at the University of 9: 16–17.
Ghent for valuable discussions on transcenden- 12. Wolkenhauer, O. 2001. Systems biology: The rein-
tal philosophy and philosophy of biology. In carnation of systems theory applied in Biology? Brief.
Bioinform. 2: 258–270.
particular, many thanks to Joris Van Poucke,
13. Mesarovic Mihajlo, D., S.N. Sreenath & J.D. Keene.
Luis Ramirez Trejo, and Franc Rottiers. 2004. Search for organizing principles: Understand-
ing in systems biology. Syst. Biol. 1: 19–27.
14. Huang, S. 2004. Back to the biology in systems bio-
Conflicts of Interest logy: What can we learn from biomolecular net-
works? Brief. Funct. Genomics Proteomics 2: 279–297.
The author declares no conflicts of interest. 15. Van Speybroeck, L., G. Van de Vijver & D. De Waele.
(Eds.). 2002. From epigenesis to epigenetics: The
genome in context [Special issue]. Ann. N. Y. Acad.
References Sci.
16. Van Poucke, J. & G. Van de Vijver. 2008. Modelling
1. Thompson, E. 2007. Mind in Life. Biology, Phenomenol- in systems biology. An analysis of the relevance of
ogy, and the Sciences of the Mind. The Belknap Press of Rosen’s relational viewpoint for current systems bio-
Harvard University Press. London, England, p. 92. logy. International Journal of Computing Anticipatory Sys-
2. Vidal, M. 2001. A biological atlas of functional maps. tems 21: 184–198.
Cell 104: 333–339. 17. Van de Vijver, G. & J. Van Poucke. 2008. Subjectivity
3. Marks, J. & B. Andersson. 2007. Foreword. In and objectivity: a matter of life and death? Cosmos
Systems Biology: a Grand Challenge for Europe. Eu- and History, The Journal of Natural and Social Philosophy
ropean Science Foundation. Retrieved October 4(1–2): 15–28.
25, 2008, from www.esf.org/research-areas/medical- 18. Moss, L. 2003. What Genes Can’t Do. The MIT Press.
sciences/publications.html. Cambridge, MA.
Van de Vijver: Complexity and Relational Thinking 317

19. Webster, G. & B.C. Goodwin. 1982. The origin of ism. Kluwer Academic Publishers. Dordrecht, the
species: A structuralist approach. J. Social. Biol. Struct. Netherlands.
5: 5–15. 22. Bourg, D. & A. Papaux. 2008. Métaphysique des
20. Rosen, R. 2000. Essays on Life Itself . Columbia Uni- OGM. Philosophie Magazine. 21: 20.
versity Press. New York. 23. Husserl, E. 1996 [1936]. The Crisis of European Sci-
21. Van de Vijver, G. (Ed.). 1992. New Perspectives on ences and Transcendental Phenomenology. D. Carr (Trans.).
Cybernetics. Self-organization, Autonomy and Connection- Northwestern University Press. Evanston, IL.