Medicine Studies

, Volume 3, Issue 1, pp 29–39 | Cite as

On the Normativity of the Immune System

Article

Abstract

In the 1940s, Georges Canguilhem has established the concept of biological normativity on the level of the organism in his key work on “The Normal and the Pathological”. We would like to present a contemporary analysis of Canguilhem’s work, set it in context with more recent results from the field of complexity and immunology, and evaluate the problematic whether normativity is a genuine capacity of the organism. Based on Canguilhem’s conditions of the definition of biological normativity, we show that the immune system as one of the complex systems of the living equally shares the capacity to be normative. We will then conclude that normativity can also be conceptually independently displayed on the level of complex systems of the living.

Keywords

Immunological Theory Concepts in medicine Georges Canguilhem Epistemology Immunology Normal and pathological 

Introduction

The concept of normativity has recently attracted a genuine interest from various fields such as analytical linguistics in the distinction of normalized and normative language, moral philosophy, and theoretical biology. The origins of normativity in society and in the human being are in question as well as its mere definition. We would like to contribute to the discussion on normativity first by analyzing the nominal definition of normativity and then by addressing it from an empirical perspective in the way it translates in the human organism.

What norms define our common life? What norms define us as human beings and how do they translate into biological norms? Social norms, industrial norms, and physiologic norms, they all share the common characteristics of a rule, they set a frame of how things ought to be. The question of the standardization of the human body, such are issues raised facing the debate on normativity. What do we understand of normativity? When we attribute normativity to an entity, it is the capacity of being normative, i.e., changing and actively creating new norms, instead of simply accepting them.

Normativity has originally been defined in linguistic analysis through “ought-to”sentences that differ from merely factual statements (“is”). The normative power of such sentences allows to state how things should be while the latter would characterize narrative ones. Normativity has been taken up in questions of moral philosophy1, but has also been connected to the theoretical discussion of disease concepts.2

Biological norms can be understood in two ways. Norms can be merely statistical, defined by the threshold of a bell curve over a population of events or they can be understood as individual settings. Physiology offers a plenty of examples of the organism’s power to establish functionality in a changing environment and therefore keep its “normative” power by changing and creating norms if necessary.

In the 1940s, Georges Canguilhem3 has successfully established the “biologic” concept of normativity of the human organism.4 According to him, biology distinguishes itself as a Science by incorporating distinct choices. Such a choice would be for the organism to choose for example health instead of disease. Starting from Canguilhem’s writings, can disease be defined on a lower level than the one of the organism? Does the primary argument automatically lie within the organism as a whole and secondary logic follows on the lower level of systems, organs, and genes. Or is it even possible to conceive a normativity that lies primarily on the level of a system? What kind of normativity can we define from an immune reaction? This question is raised, when we set Canguilhem’s idea of the normativity of the human organism into the contemporary context.

In this essay, we would like to analyze Canguilhem’s concept of normativity of the organism regarding more precisely the immune system and develop it in order to discuss the possibility of normativity, innate to complex living systems, and logically independent of the concept of the organism itself. In this approach, we chose the immune system to exemplify our hypothesis because it has been previously defined as one of the bodies’ very complex systems with non-linear interactions.5

First of all we would like to follow the example of the immune system as it presents itself in Canguilhem’s writing, in order to analyze the notion of the normal and the pathological. Then, we are going to discuss more recent aspects of immunology and finally conclude on the critical role of complex systems and their particular capacity to be normative.

Canguilhem’s Biologic Concept of Normativity

What does Canguilhem refer to when he speaks of disease and norms? Canguilhem does not distinguish the normal in the statistical sense. His “normativité” is founded in a value-oriented behavior of the human organism that enables the organism to choose and to have preferences. Such a value-oriented behavior means to take a choice in all kinds of life situations. To be clear: Canguilhem’s approach is even diametrically opposed to the statistical one. He defines the normal rather in the sense of an ideal that can only be reached by approximation. Therefore, each individual can only get close to the ideal without reaching it. But this is only one aspect of his “normativité” inspired by René Leriche’s famous quote that “health means life in the silence of the organs”.6

Although it would be insufficient to consider the normal as a stable ideal set in stone. The normal is always challenged by continuous change in the environment and in the being itself. Its mere definition is rooted in the reciprocal relation between the individual and its environment, as they are both subject to variation.

The very plasticity of the corporeal being endows it with an active role and allows the individual to escape from being trapped in a set of imposed, fixed normative forms. The latter being normative in the linguistic sense imposes itself through static imperatives.

But in Canguilhem’s terms, “the subject owns its normative character. Its individuality is at its basis and cannot be put in a fixed framework.”7 Normativity in this sense is clearly not defined statistically. It is a property of the individual based on its preferences, which are categorized as an attribute of natural beings, and it has a dynamic character. This dynamic equally has a central role in the concept of health and disease, as we will show in the following.

Normativity in this sense corresponds to a capacity; the capacity of adaptation to a new set of circumstances, to a new environment. Moreover, this capacity has to be continuously regained to remain equally active over time. Health and its maintenance are therefore active processes. It is newer assured and can always be challenged by disease. The human being chooses health over disease. Making this choice is the very own property of the organism that characterizes its outstanding role. This subjectivity of the organism is a “biological and an ontological one.”8

Analysis of Canguilhem’s “Normal and the Pathological” Regarding Immunity

In his work, “The normal and the pathological,” Canguilhem develops his concept of normativity of the organism on many levels and chooses an empirical approach to exemplify his theory. He also takes up the example of the immune system to illustrate the difference between the normal immunity and the anaphylactic shock, which he defines in the domain of the pathological. By demonstrating the possible extreme outcome, he draws the picture of a system that either tends to stabilize or to end up into a catastrophic reaction. Such a definition corresponds to the one of a complex non-linear system, which is generally capable to adapt to changing frame conditions although its non-linearity can also lead to extreme reactions.9

What is it so particular with the example of the immune system in Canguilhem’s work? He chooses a perturbed system state to which two different kinds of response exist: one is immunity the other is anaphylaxis. According to the author, “this is for example, the leading thread which allows us to understand the difference between immunity and anaphylaxis. The presence of antibodies in the blood is common for both forms of reactivity. But while immunity makes the organism insensible to an intrusion of microbes or toxins in the inner environment, anaphylaxis is an acquired supersensitivity to the penetration of a specific, particular protein, substances into the inner environment. After a first modification (by infection, or injection, or intoxication) of the inner environment, a second break-in is ignored by the immunized organism, while in the case of anaphylaxis, it provokes a shock reaction of extreme gravity, very often fatal, so sudden that it has qualified the experimental injection which provokes it with the term unleashing (déchainante), hence a typically catastrophic reaction.”10

We believe it to be necessary to look at various aspects of this long quotation. First of all, it is necessary to say that there is continuity between both states of the immune system through the mere presence of antibodies. But this hardly offers any distinction between the two states of a system that Canguilhem aims to separate conceptually. His inspiration obviously comes from the clinical picture that is clearly distinct in both states.

The paradox is the following: On the one hand, the clinical presentation is strikingly distinct for both entities. On the other hand, the individuals display continuity by the presence of antibodies as chemical constant. Although Canguilhem does not clarify the system’s physiologic or pathologic mechanisms, which has never been the scope of his work, we can clearly perceive his intention from his quote. He conceptualizes two possible orientations of the immune system. On the one hand, he brings in the subtle serological distinction between two states that clinically appear completely different. On the other hand, he does not limit his classification to a single aspect of the system. He rather tries to conceptualize a reaction encompassing the immune system as a whole. As if it were an analogy to nineteenth century experimental medicine, through lesional interventions in animal organisms,11 the immune system’s most intimate functions only become revealed at the level of its final decomposition through a “catastrophic reaction”.

The latter notion is even more interesting than the stable reaction as it immediately translates the dynamic properties of the system. Furthermore the very same notion figures in the context of theories on the modulation of complex systems.12 The non-linear character of those opposed reactions appears evident to Canguilhem who clearly denominated the latter as an “unleashing reaction.”13 Its evolution can be illustrated by a non-linear sigmoid function.

This dichotomy also reminds of Canguilhem’s critique of Claude Bernard in the numerical definition of diabetes through a glucose threshold14 and raises the question of the definition of pathology regarding the immune system. We remind that Canguilhem rejects the numerical definition of pathology with regard to the subjectivity of the individual.

On the one hand, there is the reaction of immunity, on the other hand the reaction of anaphylaxis. But which of these reactions is a normative one? If we follow Canguilhem in considering “normative” what is conductive to health of the body or of the system it would be the reaction of “immunity”.

In the above-cited quotation, Canguilhem gets close to the idea of normativity that is established starting from auto-regulated systems. A normativity of the immune system hereby becomes imaginable. This normativity is analog to the one he developed earlier regarding the pathologic states of the organism. But his quote on the immune system is not limited to the reflection on pathologic immunity or on the clinical state of immune diseases. “Physiological constants are thus normal in the statistical sense, which is a descriptive sense, and in the therapeutic sense, which is a normative sense.”15 The example of anaphylaxis is not statistically deviant, but it is therapeutically through the absence of the immune system’s capacity to be normative. The system breaks down and loses its normative capacity. The antagonism is established between immunity and anaphylaxis, which leads us to the constitution of the system.

Canguilhem’s writings have been widely recognized over the years being a reference literature for the understanding of the normal and the pathological. His reflections on immunology or on complex systems did not receive any reception to the knowledge of the authors. The discussions of concepts of immunity in the history of immunology have therefore to be considered independently.

We could therefore raise the question whether Canguilhem presents a novel approach to immunology that is not sufficiently elaborated regarding its physiologic mechanisms. It’s understanding is rooted in Canguilhem’s clinical education as a physician and his strong philosophical background: Or the system (re-) acts in the form of anaphylaxis, or it remains actively tolerant taking the form of “immunity”. Although Canguilhem’s intention was not to elaborate a theory of the immune system, he develops essential concepts to its understanding by introducing the normativity of biologic systems.

Still, we have a doubt on the true sense of the term “immunity” that Canguilhem uses. According to his descriptions, we are not quite sure if it would be more appropriate to speak of immune tolerance to translate what Canguilhem evokes in his description of immune phenomena. In a contemporary perspective, we would definitively prefer the terms of allergy and tolerance to fit in the dichotomy of a complex system of the living. The extreme form of an allergy being the anaphylactic shock has described above in an excerpt of Canguilhem’s normal and pathological.16 The concept of immune tolerance is more recent and has been heavily investigated over the last years.17

Can we argue that what Canguilhem denominates “immunity” is the establishment of a novel norm? “The new norm is not the old norm. And this capacity to establish new constants with the value of norm has seemed to us to be characteristic of the living being’s physiological aspect, we cannot admit that physiology can be constituted before and independently of pathology in order to establish it objectively.”18 We therefore can achieve a kind of normativity through setting novel constants. To Canguilhem, immunity represents indeed a change of constants as it is connected to the presence of antibodies in the blood, which is qualitatively distinct of a non-stimulated state. We would like to speak of a new constant exactly in this sense. Although “it (physiology) does not know in advance whether the new biological order will be physiological or not, but later on it will have the means to find once more among the constants those which it claims for its own.”19 What Canguilhem calls an “own” constant is a physiologic one and following his logic also a normative one. He comments: “In this sense the Kantian concept of finality is always relevant.”20

Therefore, immunity can be understood as a change of constants. Their installation is a normative process that is at the same time physiologic under the condition of being identified as an “own” constant.

For Canguilhem, the norm cannot be objective on the level of the organism. Only through its subjectivity, it can serve to accentuate the individuality of the being. In the case of immunology, the situation is analogous. The individual character of the sick is accentuated by the subjective character of disease and physiology.

Defining identity through immunologic approaches has recently been discussed among philosophers.21 We equally speak of immunologic identity when we refer to the infinite variety of HLA molecules that generally differ from one individual to another. But we doubt that this idea of identity equally implies normativity such as it becomes manifest in the organization of a complex biologic system. It seems as though it rather leads back to the philosophical definition of the person and its actions,22 an aspect which cannot be discussed in this paper.

In the tradition of French epistemology and to find further arguments in favor of his dichotomised understanding of immunity, Canguilhem introduces a historical example. He goes back to immune phenomena in the context of Robert Koch’s tuberculization experiments. In the 1890s, after having identified the tubercle bacillus, Koch tried to treat a large cohort of patients by exposing them to the immunologic mechanism of his tuberculin. There was no therapeutic effect but severe adverse effects in some patients. Tuberculin has later been identified as a powerful exposition marker for patients that had contact with tuberculosis.

Although the clinical notion of normativity remains his main focus, Canguilhem takes up Koch’s example to refer on immunity and anaphylaxis: Having ascertained that the tuberculin injection in an already tubercular subject gives rise to serious accidents, while it is harmless for a healthy subject, Koch believed that in tuberculinization he had found an infallible tool.23 In the early twentieth century, Koch aborted the experimental use of the tuberculinization for therapeutic purpose. But Canguilhem takes up his example to establish again the antagonism between two distinct kinds of reactions and evaluate those two states of immunity and anaphylaxis according to their clinical effect in the human being. Again it bridges the hypothesis of a normative action of the system to the individual clinical state of the patient. The biologic polarity actually enchains a dichotomy between the normal and the pathologic state. This tension is crucial to the establishment of a normativity of a complex system.

But Canguilhem does not limit himself in his considerations to the entity of the organism. He explicitly generalizes “normativity” as a particularity of biology as a Science. “There is no biological indifference, and consequently we can speak of biological normativity. There are healthy biological norms and these are pathological norms, and the second are not the same as the first.”24 Therefore, the author considers the normal as preferable according to the choice of the living. “This point of view is the one of the vital normativity. Even for an ameba, living means preference and exclusion.”25 But how can this choice be integrated into the organization and regulation of complex systems? Canguilhem approaches this problematic first through assuming the existence of novel constants that, as he has shown can be normative or therapeutic. Furthermore, the entity that is setting the norm equally owns a normative capacity that is innate to the biologic necessity to take choices and have natural preferences.

Such a Darwinian approach is obviously inspired by the reception of the “Origin of Species”. Canguilhem refers to it repeatedly (“(…) as Darwin had clearly seen.”).26 There does actually exist a selection in biology, which is necessarily a choice of values. Here, Canguilhem takes up the evolutionist position toward natural selection and rejects any anthropomorphism or vitalism that could have been reproached to his position.

Physiology, Pathology, and Complex Systems

For Canguilhem, the study of physiologic normativity that creates its milieu is performed in clinical medicine. This institution has the unique capacity to study the human being in its relation to pathology, to classify them by their wide variability, and to establish theories. The foremost practical work of clinical medicine is essential in this context as it is the only way to face disease in a systematic way.

For Canguilhem, disease has an impact beyond the clinical manifestations: “(…) the sick man is not abnormal because of the absence of norm but because of his incapacity to be normative. (…) Disease is a positive, innovative experience in the living being and not just a fact of decrease or increase.”27 Therefore, we cannot speak of a simple reactivity of the body when facing disease but of an active movement of the organism. Now does the organism hold a singular capacity or are other items possibly equally susceptible to express preferences? Such questions may be raised while placing Canguilhem’s work on the normativity of the organism in a contemporary context.

We will follow Canguilhem’s arguments in favor of the singularity of the organism being normative. Then, we would like to challenge this view in order to enlarge the set of entities to non-linear complex systems of the living. Canguilhem himself states that such preferences are the expression of biology itself. It is therefore not absurd to ask whether structures such as systems, organs, or even genes express similar patterns.

Canguilhem comments on Physiology and Pathology and distinguishes two essential patterns: “There are two kinds of original modes of life. There are those which are stabilized in new constants but whose stability will not keep them from being eventually transcended again. These are normal constants with propulsive value. They are truly normal by virtue of their normativity. And there are those which will be stabilized in the form of constants, which the living being’s every anxious effort will tend to preserve from every eventual disturbance.”28, that will be anxiously protected by the living of all perturbation. The latter are characterized as normal constants with repulsive value, which tend to stabilize at equilibrium and resist change that is brought from the environment. They are not normative in their normality.

In a recent analysis of the “Normal and the Pathological,” Trnka takes up Canguilhem according to whom the “real feature of organisms, an ability to discriminate between what is conductive and what is not conductive to their lives.”29 But this is precisely what Canguilhem exemplifies on novel constants, which are being recognized by physiology as its own. Such constants are considered to be normative ones. According to Canguilhem, biologic organisms hold more generally another particular capacity, namely the one to adapt by establishing two different kinds of values: propulsive and repulsive values. The latter are not normative in the evolutionary sense, as they tend to stabilize in a steady state. Whereas the propulsive values have the full normative capacity and translate into health. They have the critical ability of establishing stable conditions and re-establishing them continuously.

We would like to exemplify the normal constants at repulsive value by illustrating the natural course of chronic cardiac insufficiency as a result of, for example, aortic valve insufficiency. We think that this example is particularly suited to illustrate Canguilhem’s quotation, as it refers to one of the most essential and complex systems of the human organism: the cardiovascular system. It is object to multiple very complex regulations that encompasses different organs such as the heart, the kidneys, the blood vessels, not to mention the brain and the central nerves of sympathic and vagal regulation.

This cascade is located on several levels of regulation which are hierarchically organized. In the above illustrated case of cardiac insufficiency, the latter has a tendency to auto-aggravate. It enters a vicious circle in the aim to guarantee the body’s constants, such as an adequate blood pressure. To maintain it, the cardiac muscle pays a severe debt, which is left ventricle dilation and cardiac muscle hypertrophy. The latter necessitates a more important oxygen exploration of the muscle that leads to local hypoxia. Furthermore, the ventricle’s dilation inhibits correct heart contraction. As a result its ejection fraction, which was initially to be maintained, inevitably fades. The patient with such pathology would face his doctor because of his incapacity to perform greater physical efforts. But all treatment will come late to preserve the correct function of the cardiovascular system, which has been anatomically transformed through the underlying pathology. Kurt Goldstein, an early twentieth century German neurologist explains the organism’s reaction facing such phenomena: “There are situations in which you accept the lesion because of a certain kind of “higher” interest. In that given moment preventing this lesion is neither the most important nor the most essential task of the organism.”30 Goldstein answers with an evolutionary perspective, in which the organism is understood in terms of population biology regrouping the cells of the body. Canguilhem takes up this idea in his work on the normativity of the organism. Such value-oriented behavior is at the core of Canguilhem’s “normativité”.

Canguilhem has demonstrated that the organism possesses the structure to respond to his formal demands of subjectivity and normativity. It is evident that other levels of organization do not necessarily share the same normative capacity. On the lower level, the question has been raised whether organs or genes might also own similar capacities. But their organization is impaired in its ability to generate and adapt to changing needs. Only over generations and through natural selection change can be installed.31 Their normative capacity is therefore often limited to translate into repulsive values. This is exemplified taking into account the limited range of some organs in their adaptive power in a changing environment. The kidneys for example are functionally limited and directly depend on continuous blood flow. Its functionality is preserved in very limited margins. Genes on the other hand can only translate an adaptation through selection on the population level. They therefore lack subjectivity, which is according to Canguilhem another essential condition to real normativity.

But our scope is to focus on the normativity of complex systems of the living. A normalized system is an organized construction, an ordered organization of entities. A normative system in contrast has itself a structuring ability. Canguilhem has formulated this for the organism that “builds its own milieu”.32 The capacity of not only being passively ordered but of setting rules by itself makes a complex system of the living a normative one. The capacity of restoring norms or to establish new values at different levels is crucial especially in this endeavor.

Apart such a normative approach to the regulation of complex dynamic processes, there has been various approaches in the field of cybernetics and systems theory. In the following, we would like to discuss some of these theories in order to reveal similarities or differences to Canguilhem’s approach.

The principle of cybernetic regulation has been established by Asby in his model of a “Homeostat”33 regulator. Its principle is to maintain stable conditions in a changing environment through the definition of a “target value”. Deviance of the “actual value” from this “target value” is addressed by the Homeostat, which tends to harmonize both values. Conditions are therefore adapted until the “targeted value” is achieved. Its regulatory mechanism does also include the possibility of influencing environmental conditions. By adapting the “actual value” of a parameter X as defined by the “target value” such stable conditions are achieved. Ashby’s approach might resemble to Canguilhem’s “constants at repulsive value”. The latter are defined as constants that tend to stabilize at the same level, resisting to any change of the environment or the organism itself. But cybernetic regulation lacks the innovative principle of “constants at propulsive value”, which are really normative, according to Canguilhem.

Ludwig von Bertalanffy, an Austrian biologist, is commonly referred to as the “founding father” of system’s theory. His core work on “General System’s Theory”34 was first published in 1968. He developed general characteristics of closed and open systems and mathematized his considerations in order to create solid algorithms that enable predictions. He recognizes the dynamic quality of biologic systems, which he illustrates by non-linear interactions. Such open systems are founded in the exchange of information as Bernard Walliser states. The relation between cause and effect in such system is non-linear, which allows them to develop a particular dynamic character.35 Claude Debru has previously argued that the idea of the existence of non-linear complex systems, which establish balance on several levels, may be used to translate a concept that has been originally developed by Georges Canguilhem.36 We agree with him in this analysis and would like to show that this concept implies the possibility of such systems to be normative.

In Chaos theory, attractors play a key role in the self-organization of a system. Stuart Kauffman has importantly contributed to this theory in his Origins of Order.37 According to him, attractors exert dynamic constrains on a system and therefore have a stabilizing property as elements in their vicinity do remain close to such a fixing point, becoming inactive or stable. Given only a single attractor, a system would tend to stabilize in steady state.38 But in systems with several attractors, the situation is more complicated as transitions between attractors A1 and A2 may occur. Both are equal “attracting” points and the dynamic on the elements between both attractors can be vivid. Chaotic elements are vagabonding within the system. The “transient state” is established at the edge of chaos and stabilization of a complex system.39 Such an approach may serve to define mathematically, what Canguilhem refers to speaking of “norms at propulsive value”. On the other hand, attractors themselves lack the capacity of preference that is accorded to normative organisms. The latter may chose as a whole to prefer a state that is conductive to its health. But chaos theory modeling may still serve as a suitable tool in mathematically addressing values that tend to be normative ones. One major element of critique to Canguilhem has previously been that his philosophy including “propulsive values” precisely lacks objectivity.

What is common in these approaches is on the one hand the notion of stabilization and on the other hand extreme behavior. We would like to come back to the question of the stability of living systems and to the notion of catastrophic reactions that unveil the subject’s disease. The catastrophic reactions are according to Goldstein “reactions that never present themselves in a normal subject with the same form and in the same conditions.”40 To define the normal state of an organism, one has to consider its preferential behavior (“comportement privilégié”),41 but if one really wants to understand disease, he cannot be dispensed of understanding the impact of the catastrophic reaction. Canguilhem takes up Goldstein’s idea: “By preferential behaviour it must be understood that among all the reactions of which an organism is capable under experimental conditions, only certain ones are used as those preferred. This mode of life, which is characterized by a set of preferred reactions, it that in which the living being responds best to the demands of his environment and lives in harmony with it; it is that which includes the most order and stability, the least hesitation, disorder and catastrophic reactions. Physiological constants (pulse, arterial pressure, temperature etc.) express this ordered stability of behaviour for an individual organism in well defined environmental conditions.”42 Goldstein hereby evokes a stability of those allures of life that privileges certain reactions to minimize the appearance of catastrophic reactions. This stability becomes manifest in a process of active homeostasis. As we have shown above such homeostatic processes characterize complex systems of the living. For the example of the immune system, we have tried to show that the existence of stability but also of catastrophic reactions serves to frame the system’s non-linear interactions.

Canguilhem develops his concept referring to Goldstein who announces that “pathologic symptoms are the expression of the fact that relations between the organism and the milieu that respond to the norm have been changed by change of the organism and that many things that previously appeared normal to the organism are no more for the modified organism. Disease means tumbling and a threat to existence itself. Consequently the definition of disease demands the notion of the individual being as starting point. The disease appears when the organism is modified in a way that catastrophic reactions may arise in the milieu of its own; (…) a more or less disordered behaviour of the whole organism.”43 In this context, Goldstein refers to an individual norm that acts on the external milieu and that defines the relation between the milieu and the organism by itself (Table 1).
Table 1

Canguilhem develops an antagonism between immunity and anaphylaxis that is analogous to the one between the normal and the pathological but on a different level: the one of a complex system

Normative entity

Non-normative entity

Level of organization

Normal

Pathological

Level of the organism

Immunity

Anaphylaxis

Level of the complex system of the living

Tolerance

Allergy

Level of the complex system of the living

It is very important to recognize that the pathology is conceptualized in relation between the organism and its milieu. This relativist perspective conceives either a changing milieu or a changing organism to give source to disease. The adaptive capacity is in contrast the one that maintains health. Such a capacity can be equally found in very complex non-linear systems. The immune system as one of the bodies’ complex systems has the distinct capacity to establish a balance on several levels and to adapt to challenges from its environment. It can resist to pathology by its dynamic structure but also end up in catastrophic reactions. The communicative very structure of a complex system such as the immune system appears to be a suitable pattern to adapt Canguilhem’s theses to a broader biological horizon. The interaction with the milieu in the form of a mutual dialog becomes most evident.

The interaction of the immune system manifests an own activity, not a simple reactivity. This conception of an active immune system is conforming to the normativity of the organism, understood as an active process. The system can indeed manifest its own normativity by actively acting, by installing norms. This idea imposes itself while discussing the immune system, which is a suitable example to illustrate the impact of such very complex biological systems. It exposes notions of normativity in its composition and in its functioning and shows that the canguilhemian notion of normative capacity is not limited to the organism, but also shared by very complex biologic systems.

Conclusion

According to Canguilhem, disease is characterized by the limitation of the capacity of setting norms. For the organism, these norms have to be established in relation to its inner and outer milieu. We have tried to illustrate above that such a capacity is not necessarily limited to an organism. Complex systems of the living are equally set into an inner and outer milieu and have been proven to own abilities such as adaptation to changing environment and the capacity of establishing new norms. The given non-linear dynamics of these interactions are probably a unifying pattern of biologic interactions. As Canguilhem concludes: “Types and functions can be qualified as normal with reference to the dynamic polarity of life.”44 Ergo such biologic normativity does not necessarily need to be narrowed to the entity of the organism.

At this point, we would like to remind that the literature on complexity and system’s theory has mostly been developed after the publication of Canguilhem’s “Essai sur quelques problèmes concernant le normal et le pathologique” in 1943 and therefore could not be entirely taken into consideration. We would like to recognize Canguilhem’s pertinence in clearly deciphering systems of physiologic regulation. We have referred to von Bertalanffy’s “General System’s Theory” as key example of system’s theory.

We have tried to show that complex systems equally share the capacity of installing normal and pathologic norms, to cope with changing environment and build its own milieu. Such systems tend to install its norms in the range of normal healthy values and therefore have real biologic preferences. But it may also manifest itself with pathologic norms that inevitably lead to the clinical manifestation of disease.

Starting from the results of our analysis of the normativity of biologic systems, we would now like to confront novel perspectives from such a normative capacity. Such a normativity that is deduced from very complex biologic systems can offer novel perspectives to medicine. The choice between stabilization on the one hand and catastrophic reaction on the other is the basis of the normative character of complex biologic systems.

Measuring such an antagonism certainly remains difficult: On the normative level, it is irreducible to numbers through its subjectivity, but can be illustrated through transitory values on the quantitative level. Therefore, a light transition in relative values, that means of biologic constants, can lead to a rupture in the absolute values, which refer to the clinical image of the patient. For example, a light modification of the number of T-helper-lymphocytes in the blood can tumble down the patient’s prognosis when he is close to aplasia. There does indeed exist a choice between the privileged behavior and the catastrophic reaction.45 Given that the normal choice of the immune system is rooted in the stability of the privileged behavior, which emerges from the complex organization of its constituents, we would like to consider this behavior as an emergent phenomenon. This represents a strong normative capacity of the system by following a choice of values and acting on the entire organism.

At last, we would like to add that it is essential to establish the link between the system’s normative function and its clinical image. Only by starting from the clinic, we can be certain of the living system’s capacity to qualitative judgements. We believe together with Canguilhem that the proof of the normative character of complex living systems is regularly achieved through the clinical presentation.

Complex biologic systems present the capacity of establishing a normativity of their own. Concerning its normative capacity, the direct deduction of the system appears perfectly acceptable to us, but only being a posteriori to the clinical experience.

In an analysis of the immune system recognizing, its normative capacity has a crucial role. Conceptual change in Science is important for investigating its object. We hope that recognizing the normativity of the immune system will have an impact on the way science confronts the system.

Although we would like to conceptually broaden the capacity of biological normativity, we still confirm that the clinical manifestation of disease can by its definition only be measured on the level of the organism. Only by taking into consideration the complex global presentation of the entire patient with all his aspects, we are capable to judge about his state of health and disease. By today, there is no reliable alternative to the illustration via the clinical aspects of disease. On the other hand, it might be imaginable to develop algorithms capable of illustrating and simulating disease on the level of complex systems. Attempts to design such algorithms have already been undergone in the past, but it has been difficult to endow them with a solid predictive value on the organism’s clinical feature.

In measuring outcome in form of health and disease, we still rely on the concept of the organism. But we argue that complex systems themselves display a normativity of their own. We therefore would like to speak of a normativity of the immune system but would not go as far as to say that the immune system can be “sick” independently of its organism. The categories of health and disease remain therefore in the field of the organism.

Footnotes

  1. 1.

    A nominal analysis of the concept of Normativity has been previously established by Korsgaard (1996).

  2. 2.

    Hucklenbroich (2007: 77–90).

  3. 3.

    A very comprehensive introduction to the life and work of Canguilhem has been written by Debru (2004); alternatively: Borck (2005).

  4. 4.

    Canguilhem (1943).

  5. 5.

    Jerne (1974: 373–389).

  6. 6.

    Leriche (1936).

  7. 7.

    Canguilhem (1965: 159).

  8. 8.

    Trnka (2003: 431).

  9. 9.

    Walliser (1977).

  10. 10.

    Canguilhem (1966).

  11. 11.

    Bernard (1984).

  12. 12.

    Kauffman (1993).

  13. 13.

    Canguilhem (1978: 121).

  14. 14.

    Canguilhem (1994).

  15. 15.

    Canguilhem (1978: 68).

  16. 16.

    Canguilhem (1978: 138).

  17. 17.

    The following papers should give an overview on the field of immune tolerance: Sakaguchi et al. (2008), St. Clair et al. (2007), Keir et al. (2008).

  18. 18.

    Canguilhem (1978: 124).

  19. 19.

    Canguilhem (1978: 121).

  20. 20.

    Canguilhem (1978: 129).

  21. 21.

    Pradeu and Carosella (2006).

  22. 22.

    A developed analysis of biologic identity has been presented by: Pradeu (2006). There is an elaborated literature in the field of actions of the individual (e.g., Frankfurt HG “The Problem of Action”, American Philosophical Quarterly, 15: 157–162) but this does not take into account actions of other organized entities such as systems, which lack a single agent. Further interdisciplinary analysis would be needed in order to obtain clarification on action in such entities.

  23. 23.

    Canguilhem (1978: 124f).

  24. 24.

    Canguilhem (1978: 72).

  25. 25.

    Canguilhem (1978: 76).

  26. 26.

    Canguilhem (1978: 81).

  27. 27.

    Canguilhem (1978: 108).

  28. 28.

    Canguilhem (1978: 121).

  29. 29.

    Trnka (2003: 431).

  30. 30.

    Goldstein (1951: 178).

  31. 31.

    Hardcastle (2002: 149f).

  32. 32.

    Canguilhem (1978).

  33. 33.

    Ashby (1948: 380).

  34. 34.

    Von Bertalanffy: (1973).

  35. 35.

    Walliser (1977: 27).

  36. 36.

    Debru (1993: 113–114).

  37. 37.

    Kauffman (1993).

  38. 38.

    Kauffman (1993: 192).

  39. 39.

    Kauffman (1993: 170 ff).

  40. 40.

    Goldstein (1933: 430).

  41. 41.

    Fawcett translates “comportement privilégié” as preferential behaviour. We would like to point out that Canguilhem’s original terms state that such behavior may not only represent a preference but also be rooted in a privilege, i.e., “being invested with a privilege/special freedom or immunity/granted with a particular right or immunity”, Oxford English Dictionary, 2nd edition, Vol. XII, Clarendon Press, Oxford, 1989, p. 523.

  42. 42.

    Canguilhem (1978: 107).

  43. 43.

    Goldstein (1951: 345).

  44. 44.

    Canguilhem (1978: 137).

  45. 45.

    Canguilhem (1978: 121).

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.CIRPHLES USR 3308, Department of PhilosophyEcole Normale SupérieureParisFrance
  2. 2.Tumor and Transplantation Immunology Laboratory, Clinic I for Internal MedicineUniversity Hospital of CologneCologneGermany

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