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Enjeux théoriques et idéologiques de la prophylaxie

“Stimulate the Phagocyte”: Contested Terrains and the Birth of Cellular Immunity in turn-of-the-century Paris

« Stimuler les phagocytes » : controverses autour de la naissance de l'immunité cellulaire à Paris à la fin du XIXe siècle au début du XXe siècle
Loren K. Wolfe

Résumés

Cet article analyse la façon dont le phénomène de l’immunité a été conçu et expliqué de la fin du dix-neuvième au début du vingtième siècle en France. Il culmine avec Elie Metchnikoff, le « père fondateur » de l’immunologie. Metchnikoff a bâti cette nouvelle discipline sur le dos du phagocyte « la cellule mangeuse » – qui à la fois répond à et exacerbe le manque de synchronicité qui caractérise l’existence de l’homme. Son exploration rejoint des discours de décadence qui soulèvent des angoisses concernant la définition et la défense du « soi » dans un monde sans transcendance en demandant comment faire en sorte pour que l’homme moderne puisse accéder à un sentiment d’harmonie face à sa vie inexorablement délimitée par le temps et la biologie.

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  • 1 George Bernard Shaw, The Doctor’s Dilemma, Middlesex, Echo Library, 1906, p. 15.

1“Stimulate the phagocytes. […] [T]hey devour the disease; and the patient recovers”, instructs Doctor Bonington in The Doctor’s Dilemma, George Bernard Shaw’s 1906 satire that raises the question of who, in the face of limited resources, deserves treatment, which treatment, and at what cost1. But, as the good doctor learns, stimulation requires a light touch. Peering over his patient’s pallid corpse, the blundering practitioner wonders if he hasn’t administered too much “anti-toxin”, inadvertently expanding the voracious phagocyte’s palette: “Have we over-stimulated the phagocytes? Have they not only eaten up the bacilli, but attacked and destroyed the red corpuscles as well? [...] [H]ave they finally begun to prey on the lungs themselves? Or on one another?”(52). Shaw’s usage of the contemporary medical lexicon demonstrates how medical and literary discourse intermingled at the turn of the twentieth century. Here, medical vocabulary - vaccination, virus, microbe, inoculation, and even the newly christened phagocyte - have spilled over from the medical domain and entered the literary imaginative stream.

  • 2 Alfred I. Tauber, Immunity: The Evolution of an Idea, New York, Oxford University Press, 2017, p. 1 (...)
  • 3 Jon Turney, “Beyond Cell Wars,” Aeon, 28 March 2016, consulted 17 July 2020, on-line: https://aeon. (...)

2Clearly, Shaw had read Elie Metchnikoff, or at least knew of his “discovery” of the phagocyte, the superstar cell patrolling the “front lines” of the organism. Indeed, Metchnikoff was the first to describe the body’s encounter with the microbe as a defensive, bellicose reaction; immunity marked the hard-fought triumph over the invader. Over the last fifty years, a number of phenomena ‒ HIV, autoimmunity, the appearance of novel viruses (Ebola, SARS, Zika and most recently COVID-19), not to mention the miracle of organ transplants and the successes of immunotherapies – have challenged this widely accepted paradigm. According to Alfred Tauber, physician and leading theorist of immunity, the new field of eco-immunology views protection as just one of the immune system’s functions; its foremost duty is to process information so as to sort and coordinate responses2. As Jon Turney remarks, “much of the adaptive immune system is now discussed […] in terms of conversation, negotiation, cooperation, even diplomacy”3.

  • 4 Susan Sontag warns of the real consequences wrought by metaphorizing illness, beseeching readers to (...)

3Linguistic choices – vocabulary, metaphor4, and syntax – determine how we not only describe scientific phenomena, but also carve out the epistemological constructs we use to understand – and thus manipulate or manage – them. Evelyn Fox Keller spells out the importance of language as a social construct, fixing epistemological paradigms, determining the questions we ask and the ways we go about solving them:

  • 5 Evelyne Fox Keller, Secrets of Life, Secrets of Death: Essays on Language, Gender, and Science, New (...)

Language simultaneously reflects and guides the development of scientific models and methods. It also helps shape the ends toward which science aims, if only because we gravitate to problems we’re equipped to formulate and solve. But language is hardly free. […] The language of scientists is limited by what they learn to think and say as individuals, as members of a discipline, and as members of one or, more usually, several larger communities; it is simultaneously limited by what they can do, individually and collectively, in their ongoing material interactions with the objects of their inquiry.5

4In what follows, I will analyze the imaginative and linguistic work at play as I trace immunity in late nineteenth to early twentieth century France, culminating with Elie Metchnikoff and his phagocyte. Metchnikoff founded a new discipline on the back of a small, ravenous actor, positing the “eater cell” (etymology of phagocyte) as both the solution to and problem exacerbating the body's lack of synchronicity with itself and its surroundings. His inquiry rejoins discourses of decadence in its ontological anxiety about what determines self from other and how to go about restoring “harmony” – i.e. intactness and integrity, organismal and otherwise – to fundamentally disharmonious man, whose very constitution harbors agents undermining his survival.

5I will begin broadly by discussing how secularization in Europe during the nineteenth century resulted in an eschatological reformulation of man’s condition. This interpretation of earthbound human existence – its end and its meaning – sparked an intense interest in the body’s internal workings, particularly its ability to lengthen life by resisting disease. These investigations led to the articulation of biological immunity, the prophylactic force inherent in the body that stops illness before it takes hold. I will then track preceding and competing theories of immunity, highlighting tensions between the French and German schools and exploring disagreements within the French tradition about whether the internal body is passive or active. Finally, I will examine Metchnikoff’s poetics of the phagocyte, taking stock of the evolution of language as the imagined cell increases in both complexity and normative functioning. Stimulated by an invasive microbe, the phagocyte – both part of and autonomous from the body – exhibits a surprising relationship to time, the question at the heart of “prophylactics”; a prophylactic prevents, an anticipatory action (from the Latin prae “before” + venire “to come”). The phagocyte intercepts and digests an invader without the body “knowing”; it slows time by extending life. However, if too “excited”, the phagocyte – primitive and wild – can run amok, cause capers, and speed up aging: actions the body is ill-equipped to “prevent”. Its standing is ambivalent. Analogous to Freud’s unconscious to the extent that it eludes will and self-consciousness (though without the unconscious “tells” of lapsus, dreams, and drives), the phagocyte constitutes an internal force often at odds with its “host”. Its powers far exceed its ostensible role as a humble, hungry prophylactic agent; it not only defends, but defines – and undermines – the singularized self, upending the modern ideal of an autonomous, self-same, and singularized individual.

The Modern Imperative: Prolonging Life

6A wave of secularization swept over Western Europe during the course of the nineteenth century, leaving, in its wake, the modern embodied self. Without the promise of eternal salvation for the individual, biological death came to coincide fully with the end of life. Human energy and enterprise shifted from securing a place amongst loved ones in paradise to ensuring and prolonging individual earthly survival. Margaret Lock eloquently summarizes the stakes involved in this paradigm shift:

  • 1 Margaret Lock and Vihn-Kim Nguyen, An Anthropology of Biomedicine, Oxford and Malden, MA, Wiley-Bla (...)

[W]ith secularization, keeping death at bay became a source of meaning in life - the ideas about transcendence were internalized and individualized, and the ‘soul’ was displaced by the self-reflective, rational mind so characteristic of modern society in the West. […] [T]he life course of individuals began to be conceptualized as a finite unit of biological time, rather than as […] transcendental intergenerational ties linking the living and the dead.1

  • 2 Evelyn Fox Keller, Making Sense of Life: Explaining Biological Development with Models, Metaphors, (...)

7To understand how to maintain a human’s life – i.e. its bodily and psychic integrity – science first had to respond to the most fundamental question: what is life?2. The term biology – the study of life – was coined at the beginning of the nineteenth century by two scientists, one German, one French (Gottfried Treviranus and Jean Baptiste de Lamarck, though independently of each other), when it became clear that Enlightenment classification systems failed to explain how life is “born” and how it develops. Across Europe, scientific attention turned from making and documenting taxonomic observations to deciphering the functional processes at the heart of “life”. Germans took the lead in the 1830s when Theodor Schwann and Matthias Jakob Schleiden identified cells – the most basic, indivisible units in the body – as the fundamental elements organizing all living creatures (plants and animals). Rudolf Virchow, the “father of modern pathology”, later proved in 1855 that all cells derive from other cells.

  • 3 John Andrew Mendelsohn, Cultures of Bacteriology: Formation and Transformation of a Science in Fran (...)
  • 4 NIH-U.S. National Library of Medicine, Gallery Dream Anatomy, Der Mensch als Industriepalast” (“Ma (...)

8Methodological practices and scientific assumptions split along French and German lines, a rivalry that would determine the evolution of biological sciences – including immunology – for over a century3. The basic tenets of the two conceptual frames remained constant, shaping what would later become the quarrel between the French (with a dash of Russian) cellularists and the German humoralists about the mechanisms of immunity, which I will explore shortly. The German school viewed biological life in purely atomistic terms, reducing it to its physical, observable, measurable properties where the body works according to mechanical, predictable rules (as beautifully represented in Fritz Kahn’s 1926 drawing of Der Mensch als Industriepalast, or Man as Industrial Palace4).

  • 5 John Andrew Mendelsohn, “Medicine and the Making of Bodily Inequality in Twentieth-Century Europe”, (...)
  • 6 Arnault Tzanck, « La notion de terrain : Son importance doctrinale », La Presse Médicale, n° 16, 24 (...)
  • 7 Ibid., p. 317. Evoking the interaction between a pathogen and le terrain, Tzanck points to this per (...)
  • 8 John Andrew Mendelsohn, “Medicine and the Making of Bodily Inequality”, op. cit., p. 24.

9In contrast, the French school, led by Louis Pasteur, grew out of an “agricultural” tradition by which microorganisms were seen to coexist with other forms of life. It maintained a belief in the ecologically necessary role of microbial life. The notion of le terrain exemplifies this mindset – conjuring rich associations with land, soil, and fertility. Le terrain began circulating in the medical context during the last decade of the nineteenth century5. By the 1930s, its definition tottered between the “animated material” of “the host body”, “heredity”, or a “pre-established harmony”6. It is composed of living tissue endowed with powers of perception and memory7. Le terrain corresponds roughly to what Anglophones would understand by the word “constitution”, an inherited pre-disposition that renders a person more or less susceptible to getting sick from a particular illness. It raises the question of “differential reactivity, of essential inequality”8, where individual bodily terrains vary from person to person. For this reason, French scientific production, more so than other national schools, was preoccupied with the inside of the body – its individualized, biological “plots” – and how to fortify it by tending the terrain, an interest that eventually led to Metchnikoff’s conception of cellular immunity and the birth of what has become the science of immunology.

Immunity as Exception - Immunity as Protection

  • 1 Timothy Campbell, “Bios, Immunity, Life: The Thought of Roberto Esposito”, Diacritics, vol. 36, n°  (...)

10Immunity, as a concept, straddles the juridical and biomedical realm. In The Oxford English Dictionary, “immunity” is first defined in its legal sense: “Exemption from a service, obligation, or duty; freedom from liability to taxation, jurisdiction, etc.; privilege granted to an individual or a corporation conferring exemption from certain taxes, burdens, or duties (in later use esp. from prosecution or arrest)”. An individual who has immunity remains part of a given community while being exonerated from the obligations such adhesion normally requires. He (I am consciously maintaining the pronoun – historically, legal immunity has benefitted mostly men) enjoys the advantages of communal inclusion, while at the same time being released from full participation in and accountability to it, as in the case of diplomatic immunity or immunity from prosecution. This definition of immunity extends far back to the Roman Empire when certain populations – ironically including doctors – were exempted from having to perform vital public services, for example paying taxes or serving in the military1.

11Semantically, immunity, as a biological phenomenon, has a much shorter history, evolving and acquiring importance over the course of the nineteenth century. At mid-century, the medical meaning of the word was not the dominant one, and, in most cases, to evoke this sense, the noun was preceded by the adjective “morbid”, differentiating it from parliamentary or ecclesiastical immunity. People understood immunity in terms of two phenomena: firstly, by the observation that once a person is infected with certain illnesses – smallpox or chickenpox, for example - and survives, he or she is unlikely to get sick from the same sickness; secondly, that, for whatever reason, some people do not succumb to an illness – they demonstrate an inherent resistance.

12The science of immunology, dedicated to studying organismal defense and definition, arose out of questions about the idiosyncratic response to illness or other external “invasion”. As mentioned above, the German school embraced what has been dubbed the “humoral” perspective, reducing life to its physical, measurable properties. In 1891, Robert Koch, the father of germ theory, was appointed director of the Institute for Infectious Diseases (the name changed to the Robert Koch Institute in 1942), the German equivalent of L’Institut Pasteur. Koch approached microorganisms as pathogens to be eradicated. Paul Ehrlich, hired by Robert Koch in 1891, proposed that immunity resulted from invisible, purely chemical neutralizations of the germs. These interactions occur without the intervention of cells or any other “unpredictable” bodily element deemed “vitalistic”. They are observable – and reproducible – through test-tube experiments with blood serum, the liquid component of blood from which cell – thus living – matter has been entirely removed.

13From the mid-nineteenth century on, the French school, meanwhile, pursued more “organismal” hypotheses. It framed immunity as a result of “live”, observable cells acting upon other cells in a dynamic process. Here, the interaction between the outside and inside of the body was of vital importance. It animated the work of Claude Bernard, the “father” of experimental medicine, during the 1850s and 60s, and subsequently Louis Pasteur, who established his eponymous Institute in 1887 (four years before Koch) as the preeminent site for scientific research related to vaccines and pathogens. In 1888, Pasteur appointed Elie Metchnikoff, the eccentric Russian scientist, to lead the new Immunology laboratory.

From Chrestien’s Failed Receptivity to Pasteur’s Visible Germs

14André-Thérèse Chrestien, a Montpellier physician and dedicated vitalist (to the extent that he rejected scientific trends reducing the body to a machine), wrote one of the first theses in France on immunity in 1852. Under the title De l’immunité et de la susceptibilité morbides au point de vue de la clinique médicale, he argues for treating “morbid immunity” as a clinical concept, the antonym of “morbid susceptibility” or the condition by which one is rendered “susceptible” to death. According to Chrestien, for disease to manifest, the internal environment must be “receptive” to noxious elements in the surroundings; immunity indicates a lack of such receptivity, a “failure” to engage and submit. Ed Cohen extrapolates on this abortive interaction:

  • 1 Ed Cohen, A Body Worth Defending, Durham, Duke University Press, 2010, p. 214 (my emphasis).

[I]mmunity bears no particular positive or substantial import; it does not represent an active engagement of the organism, let alone an active defense, merely denoting the failure to be affected by illnesses […] In other words, immunity serves here as a descriptive recognition that environmental catalysts lack efficacy if a ‘certain capacity or disposition’ of the human body to fall ill does not realize itself.1

  • 2 André-Thérèse Chrestien, « De l’immunité et de la susceptibilité morbides, au point de vue de la cl (...)
  • 3 Chrestien was the first to distinguish between innate and acquired immunity, terms that have surviv (...)

15Immunity for Chrestien is a passive, even a missing trait: « la faculté […] de ne pas contracter certaines maladies ou même de n’en contracter aucune […]. Cette exemption est due à une force de résistance plus ou moins inhérente à la vie. »2 In this way, Chrestien’s usage ties the legal and the medical meaning together: immune is he who is exempt from death by disease precisely because he is non-reactive3.

  • 4 Louis Pasteur, Pasteur : Écrits scientifiques et médicaux, éd. André Pichot, Paris, GF Flammarion, (...)
  • 5 Bruno Latour, Pasteur : guerre et paix des microbes suivi de Irréductions, Paris, La Découverte, 20 (...)

16The development of microbiology between 1870 and 1900 shifted causal understandings of sickness and immunity. Pasteur’s experiments on fermentation proved the existence of le germe – a living, invisible agent – while his experiments depriving sterile, sealed-off cultures of air disproved the theory of spontaneous generation. For Pasteur, the “germ” was life and life’s becoming: « La vie c’est le germe avec son devenir, et le germe c’est la vie. »4 Bruno Latour describes Pasteur’s program as a formidable translation of hygienic principles (i.e. the belief that each individual is tied and responsible to those around him) organized around manipulation of the germ/microbe. Once it became possible to vaccinate using an attenuated version of the microorganism, the hygienists jumped on the vaccination bandwagon with the mantra: « Nul n’a le droit de contaminer autrui. »5

  • 6 Louis Pasteur quoted in Bruno Latour, op. cit., p. 34.

17Politically, the drive to uncover and combat noxious and invasive elements corresponded with the push for French bodies (together composing the French social body) to recover and “regenerate” in the wake of France’s loss to the Prussians. Pasteur, for his part, hoped to mobilize science in the service of curing what he called the Prussian “chancre”6. The pasteurization of France perfectly channeled the values of solidarity promoted under the Third Republic by which each member of society is responsible to the other members; all are mobilized behind a common goal of national revitalization.

18France’s expansionary efforts (pursuing its colonizing program while boosting its “home-grown” population) hinged on recognizing – so as to master – the microbe. Bruno Latour calls Pasteur « le montreur de microbes » precisely for this “accomplishment” (59), Pasteur’s greatest according to Latour. Building on the work of Edward Jenner (generalizing what, for Jenner, was a singular phenomenon), Pasteur focused his energy on “revealing” the microbe. By rendering it “visible”, he tamed it as much in “actuality” (by physically manipulating it, lessening its strength) as in the imaginary, where its existence exerted the most force. He did so by staging the laboratory as a théâtre de la preuve (in the same vein as Charcot’s leçons de mardi at la Salpêtrière). The in vitro (versus in vivo) methods Pasteur used reinforced the ideology of visibility and also established Pasteur as the indisputable “master of ceremonies” of his theater, or, to use a political metaphor, the great civilisateur in his efforts to “cultivate” his microbial/bacterial “cultures”. Ironically, Pasteur made prophylactic measures, demure when compared to the more brazen appeal of other treatments (surgery or bloodletting, for example), sexy, spotlighting their understated power to prevent illness from showing itself.

19By centering his scientific enterprise on this cunning if uncouth character, Pasteur skirted traditional pigeonholing. He reinforced his polyvalence by creating and publishing the Institute’s Annales in which the microbe starred as a versatile actor maneuvering from one scientific discipline to the next: « [Les annales] peuvent […] sans se disperser faire porter tous leurs efforts sur les quelques points d’hygiène, de biologie, d’administration, de pathologie sur lesquels le laboratoire leur permet d’être les plus forts […], ils peuvent passer d’une discipline à l’autre » (141). The discipline-neutral laboratory permitted all of the cross-pollination exercised by microbiological studies. By focusing on the multifarious microbe, Pasteurians succeeded in revolutionizing both medicine and hygienic policy without getting bogged down in unsavory, “real-life” aspects: « [Les articles des Annales] vont renouveler la médecine sans jamais prendre la maladie comme objet d’étude et renouveler la politique et l’hygiène sans jamais prendre l’homme pauvre ou déchu comme unité d’analyse » (170).

20Trickery is involved in the Pasteurian paradigm; the microbe, the external “morbid” agent attenuated by Pasteur’s treatment (what Latour labels as « le microbe-cultivé-dont-on-fait-varier-la virulence » [168]) “compromises” itself by signaling its presence to the terrain: « C’est le microbe lui-même, un peu affaibli, qui va servir d’agent double et qui va, en allant prévenir le terrain immunitaire, trahir ses compagnons » (139) (my emphasis). The microbe gives warning, a form of self-sabotaging prevention; it is its own prophylactic. However, Pasteur does not make the conceptual leap to understanding immunity as an active process. He maintains the language of negativity, seeing immunity as a passive state attained when the invasive microbes have exhausted the “nutrients” the now immune body has to offer. Any future microbes of the same kind will die of “famine” when encountering the body still exhibiting signs of nutritional “depletion”. He uses this imagery of feeding – imagery Metchnikoff will later seize – when explaining the way his “cultured” microbe/virus secures immunity in the “Pasteurized” body, and why this immunity is time-stamped:

  • 7 Caesium and Rubidum are relatively rare elements that were discovered by Robert Bunsen and Gustav K (...)
  • 8 Louis Pasteur, Œuvres, éd. Pasteur Vallery-Radot, 7 volumes, Paris, Masson, 1922-1939, VI, p. 315 ( (...)

À ceux qui s’étonnent de la durée limitée de l’immunité après l’inoculation de certaines maladies contagieuses, je répondrai ceci, car on peut aller loin lorsqu’on imagine : supposons que le caesium et le rubidium7 soient des éléments nécessaires à la vie des microbes-virus de la maladie dont il est question : qu’il en existe une petite quantité dans les tissus de l’animal inoculé et que cette petite quantité ait été consommée par une première culture du microbe-virus dans l’organisme inoculé, cet organisme restera réfractaire à une nouvelle inoculation jusqu’à ce que les tissus aient récupéré […].8

21Pasteur exchanges the word “immune” for « réfractaire ». This lexical choice reinscribes the body into the political realm as a subordinate, albeit a recalcitrant one, since the most common definition of « réfractaire » is of a body (an individual) who refuses to “submit” to authority. The virus exerts external, determinative pressure. The body, depleted, shores up its forces, running the risk of having its insides “eaten” again.

  • 9 Émile Roux, “Jubilé Metchnikoff,” Annales de l’Institut Pasteur, 29, 1915, p. 357.

22The microbe’s powers of fascination were “attenuated” for Pasteur once they passed under the “passive” skin. Unlike immunity gained through smallpox inoculation, which left a “battle” scar via the pockmark, the microbe, in vivo and thus invisible, left no trace of its “work”. Having reached his conceptual limits, Pasteur happily handed off serious consideration of the phenomenon to Elie Metchnikoff, the eccentric Russian zoologist/biologist/embryologist, giving him his own lab to elaborate his « doctrine de l’immunité »9.

Metchnikoff’s Famished Phagocyte

  • 1 Anne-Marie Moulin, Le Dernier langage de la médecine : Histoire de l’immunologie de Pasteur au Sida(...)
  • 2 See Alfred I. Tauber and Eileen Crist, “The Phagocyte, the Antibody, and Agency in Immunity: Conten (...)

23Metchnikoff was an “ennemi d’un ennemi” 1, having proposed a competing, cellular-based paradigm for immunity to the humoral, chemical explanation championed by Robert Koch and Paul Ehrlich (with whom Metchnikoff shared the Nobel Prize in 1908). Ehrlich championed the “antibody” (a name that spectacularly negates life) as the chemical agent responsible for neutralizing invasive cells, a substance with no “purpose” or “movement” of its own, prophylactically “ejected” into the organism’s internal fluids as a reactive agent2.

  • 3 See Alfred Tauber’s discussion of German reductionism in The Immune Self, Theory or Metaphor?, Camb (...)

24Ehrlich criticized Metchnikoff’s protean phagocyte for its “agency” and “teleological purpose”3. And, indeed, this small cell does bear heavy responsibilities: it protects the organism, ensuring its integrity, while at the same time redrawing the lines of what does and does not count as integral.

25In his 1903 text Études sur la nature humaine, Metchnikoff paints the phagocyte as a “supercell” possessing extraordinary abilities:

  • 4 Élie Metchnikoff, Études sur la nature humaine. Essai de philosophie optimiste, Paris, A. Maloine, (...)

Dans toutes les parties de notre corps, il ne manque pas de cellules ayant conservé beaucoup de leur indépendance. Elles possèdent leur mobilité propre et sont capables de dévorer toutes sortes de corps solides, ce qui les a fait désigner sous le nom de phagocytes ou cellules voraces. Ces phagocytes remplissent un rôle très important dans l’organisme : ce sont eux qui se réunissent en grand nombre autour des microbes ou de différents autres intrus capables de nuire à notre santé, et les dévorent […]. Les phagocytes sont doués de sensibilité propre. Ils ont une sorte d’odorat ou de goût qui leur permet de reconnaître la constitution du milieu qui les entoure. Selon l’impression ressentie, ils s’approchent des corps qui la provoquent, restent indifférents ou même s’en éloignent.4

  • 5 Ibid., p. 352.

26With its keen sense of smell, the phagocyte “sniffs out” any “intruder” that dare set foot on his terrain, rushing to the trespassed area, engulfing and devouring the offender. The story of Metchnikoff's “discovery” of these cells in 1883 – he pierced the translucent skin of a starfish larva with a rose thorn to watch these “mobile” cells race to the scene of infiltration – is one of immunology's founding myths. The body remains ignorant of the phagocyte’s activities: « Nous n’avons aucune sensation de la lutte permanente que nos phagocytes mènent contre les microbes qui tendent constamment à nous envahir. »5 Most importantly, Metchnikoff overturns Louis Pasteur's assertion of bodily passivity in the face of an avid, nutrient-starved microbe. He gives the “host cells” “the chops”, so to speak; they – not the microbes – do the chomping.

  • 6 Metchnikoff, « Sur l’état actuel de la question de l’immunité dans les maladies infectieuses. Confé (...)

27Metchnikoff built his whole theory of immunity around the phagocyte, emphasizing the role it plays in determining the body’s terrain, a site of constant movement and change. He reinterprets Darwin’s theory of competition and survival for the theater of internal corporality where the heroic phagocyte squares off against the offending “morbid agent”: « D’après cette hypothèse, la maladie se présenterait commme une lutte entre l’agent morbide, le microbe venant du dehors, et les cellules mobiles, propres à l’organisme. La guérison résulterait de la victoire de ces cellules et l’immunité serait la manifestation de leur activité, suffisante pour empêcher l’invasion par les microbes. »6

  • 7 Leon Chernyak and Alfred I. Tauber, Metchnikoff and the Origins of Immunology: From Metaphor to The (...)

28While this narrative highlights the phagocyte's role in protecting the organism, Alfred Tauber and Leon Chernyak emphasize the even more essential definitional function the cell performs: “The cardinal point to be elucidated is how Metchnikoff established an entirely new vision of the organism, one that arose from a potentially disharmonious evolved self made up of elements that had to be harmonized. For Metchnikoff, the phagocytes served as the principal harmonizing element; from the formulation, the basis of Self emerged and immunological defense and surveillance were born. More broadly, the idea of selfhood was revolutionized.”7 Tauber and Chernyak convincingly argue that the phagocyte not only defended but determined self from other, only secondarily eliminating the latter. It did so with the intention of restoring harmony to a fundamentally disharmonious being.

Man and His Disharmonies

  • 1 Metchnikoff, Études sur la nature humaine, op. cit., p. 33. Again demonstrating the porous boundari (...)

29Immunity, by virtue of the lines of inquiry it solicits, often compels scientists devoted to its study to moonlight as philosophers; Metchnikoff is perhaps the first example of this form of hybrid thinker. In addition to penning several scientific monographs on immunity, he also produced two “philosophical” works dedicated to analyzing the “disharmony in man”. Études sur la nature humaine (1903) followed by Essais optimistes (1907) grapple with the fundamental questions: why is human nature so profoundly out of sync with both itself and its surroundings? Why can’t man be like the digger wasp, which exists in perfect harmony with its environment and does so with “admirable mores”1? Man, comparable to the Icarian night moth drawn to light only to have its wings burnt (Études, 46-47), exhibits, in his morphology and drives, any number of inexplicable traits and behaviors that do not ensure survival or species’ propagation: masturbation is futile (122-123); the hymen and the lack of a penile bone work against procreation (104-105); or, more seriously, the “family instinct” fails to prevent a woman from seeking an “artificial” abortion (136-137). Moreover, Metchnikoff asks, in concert with Rousseau: why do only old people appreciate life`? In terms of prophylactics, Metchnikoff’s interests moved beyond immunity, per se, more ambitiously seeking to stave off the effects of pathological aging (he even coined the term “gerontology”) enough so that man would reach a harmonious point before death, experiencing « l’accomplissement du cycle complet et physiologique de la vie, avec une vieillesse normale qui aboutit à la perte de l’instinct de la vie et à l’apparition de l’instinct de la mort naturelle […] » (377).

30An unfaltering positivist, Metchnikoff argues that science is best equipped to improve these conditions and, as we discussed, posits the phagocyte as the key player, though ambivalently. Metchnikoff’s portrait of this cell increased in complexity. He splits the phagocytes into two groups: the microphages (the cells that lead the attack against microbes) and the macrophages (the “housecleaners” that sop up blood from hemorrhaging and other mechanical lesions [313]). While, in general, their role is beneficial (313), if the macrophages, in particular, become overexcited, they begin ingesting the body’s noble elements (315) (nerve cells, for example, causing senility) – a destruction that accelerates aging. He offers a vivid example of a macrophage going rogue, making hair turn gray:

Les cheveux colorés sont remplis de grains de pigment, disséminés dans les deux couches qui constituent le cheveu. À un moment donné, les cellules de la moelle des cheveux commencent à s’agiter ; elles sortent de leur torpeur et se mettent à dévorer tout le pigment qui est à leur portée. Bourrées de grains colorés, ces cellules qui constituent une variété de macrophages (désignés sous le nom de pigmentophages, ou mieux encore de chromophages), deviennent mobiles et quittent le cheveu, pour se diriger tantôt dans la peau, tantôt en dehors de l’organisme. De cette façon, les chromophages transportent avec eux le pigment des cheveux qui nécessairement deviennent incolores, blanchissent. Le mécanisme du blanchiment des cheveux et des poils présente ce côté important qu’il indique une surexcitation des macrophages comme phénomène prédominant dans la dégénérescence sénile. (317, my emphasis)

31Here, the agricultural metaphor (the “hair grains”) tints Metchnikoff’s getaway scenario. And we uncover George Bernard Shaw’s source, warning of the dangers of overstimulation! To ensure a long life (and a “non-pathological” old age), according to Metchnikoff, man’s phagocytes must be managed carefully, their “aggressive tendencies” weakened (320).

  • 2 Kirill Rossiianov makes a compelling argument about race, reading into Metchnikoff’s formulation of (...)

32In an illuminating article, Kirill Rossiianov identifies the phagocyte as the “primitive element” in man. As long as man (a relatively “young” species) exhibits evolutionary “growing pains” (the source of his “disharmony”), he retains his more “atavistic” traits; this is particularly true of "civilized" man who encounters the most disharmony between his “high” and “low” elements. Metchnikoff establishes a paradoxical hierarchy: while a push toward civilization is preferable, “lower” states of being exist in greater harmony2. His formulation of the phagocyte reinforces a notion of a “division of labor” in the body where the most “primitive” cells perform the most vital, “protective” functions; but they also have the potential to run amok. With each “ingestion” by the phagocyte – whether of a “malicious”, microbial cell or of a “noble” cell perceived as effete or damaged – the organism, however minutely, changes form, remaining in a state of constant redefinition.

  • 3 Anne-Marie Moulin, Le Dernier langage de la médecine, op. cit., p. 400.
  • 4 Metchnikoff, Essais optimistes, Paris, A. Maloine, 1907, p. 269.

33Anne-Marie Moulin compares the immune system, with the phagocyte at its core, to « la moderne version des Méditations cartésiennes, la genèse du moi et du monde […] l’indispensable mythe de la naissance de l’Égo »3. But, unlike Cartesian meditations, the phagocyte’s work eschews reason. If the immune system gives birth to the biological Ego, it does so without the Ego having much say over its emergence or its development. I am tempted to go a step further and frame the immune system as a biological unconscious, an invisible and unpredictable force that “protects” through “repression”, acts on primal instinct, and undermines the subject if too excited. Though Metchnikoff does not mention Freud, he has a section of Essais optimistes dedicated to psychic phenomena – citing somnambulism, hysteria, and crowds – as moments where fear awakens long extinguished survival mechanisms: « [L]’homme est peut-être capable de récupérer ces sens de nos ancêtres éloignés et de savoir des choses que nous ignorons à l’état normal. »4

  • 5 Jean Claude Ameisen, La Sculpture du vivant : Le suicide cellulaire ou la mort créatrice, Paris, Le (...)
  • 6 Anne-Marie Moulin, Le Dernier langage de la médecine, op. cit., p. 400.

34The phagocyte is the biological equivalent of these primitive psychic states. It knows what the conscious body ignores and responds accordingly, warping time. Jean Claude Ameisen analyzes the cell’s uncanny ability to “know” the other before it encounters it, exhibiting its “pre-science”. He argues that this pre-knowledge is the result of « la mémoire, l’empreinte qu[e le système immunitaire] conserve […] de la nature de notre identité », an biological identity that precedes our birth: « C’est au travers d’un jeu fascinant avec le hasard et la mort que se construit en nous une armée de cellules qui paraît dotée du pouvoir étrange de prévoir l’avenir […] »5. Endowed with a pre-existing impression of self, the phagocyte’s “normal” powers of protection through ingestion slow down the clock. Overstimulation speeds it up as the cells nibble the “noble elements” and make the body age prematurely. As the “culmination” of « les caractéristiques de l’âme et de l’organisme »6, it represents the force through which biological self in the world gets negotiated, becoming ever other. As such, the immune system is seen more and more as a medium to be manipulated and controlled even as a full comprehension of the mechanisms by which it works continues to elude us.

Legacy and Language

  • 1 These two phenomena were immune tolerance (the lack of a response of the immune system to a “non-se (...)

35Metchnikoff’s cellular-based understanding of the immune system, with its emphasis on immunity’s identity conferring role, fell out of favor when it failed to account for the phenomenon of immune specificity (the ability of the immune system to “recognize” and “eradicate” specific microbes while tolerating others). The competing German model, proposed by Paul Ehrlich, gained widespread acceptance for much of the first half of the century. Metchnikoff’s phagocyte wouldn’t find its relevancy again until the mid-nineteen forties when Frank Burnet, an Australian virologist, returned to Metchnikoff in his investigations of two phenomena for which he was unable to find an explanation using the humoral paradigm1. Burnet confirmed immunity as a biological (i.e. cellular) endeavor and also elaborated a theory – Clonal Selection Theory – accounting for immune specificity through the passing on of an immune “memory”. Burnet proposed that cellular encounters with antigens would become recorded into the biological makeup of the cell, itself, and thus get reproduced through cell division, expanding the repertory of antibody production in later cell lineages. In 1949, based on his observations, Burnet formally introduced the term self/non-self into the immunological lexicon (Metchnikoff never made this ontological leap in his writing, only ever employing the neutral term “organism”) and confirmed the role of the immune system as the primary regulator of biological identity.

  • 2 In his most recent work, Tauber has revised his understanding of an immune self, replacing the noti (...)

36Based on Burnet’s work, the immune system was cast as a sister to the nervous system, and, eventually, as a complex auto-regulated system constantly having to balance auto-preservation from auto-destruction. Endowed with its own cognitive functions of perception and memory, not to mention an ability to “learn”, the immune system assumed the epistemological task of “knowing” the borders of the biological self, or at least being able to “identify” what did not belong. But more than just “knowing” the self, as Albert Tauber has very convincingly claimed, with every decision either to “eliminate” or to “integrate”, the immune system also ontologically constitutes the organism, redefining its borders2.

37In Nietzsche et la biologie, philosopher Barbara Stiegler argues that cellular theory, by eroding the myth of anatomical unity, undergirds the humble step away from the primacy of a centralized consciousness, what Nietzsche calls la « phase de modestie de la conscience ». Citing Virchow, Stiegler writes : 

  • 3 Barbara Stiegler, Nietzsche et la biologie, Paris, Presses Universitaires de France, 2001, p. 23.

Avec la théorie cellulaire, toute centralisation anatomique se révèle être un leurre, qui dissimule la multiplicité que nous sommes, et dont la conscience est la grande responsable. Mais avec la conscience, c’est la philosophie de l’Ego, celle qui, avec Descartes et Kant, commence par le Je, qui est mise en accusation. Virchow propose alors de renverser la perspective. Il est temps de comprendre que « le “Je des philosophes n’est qu’une conséquence du “Nous des biologistes ».3

38Taking this statement one step further, the “I” of philosophers is only a consequence of the “we” of biologists who are only the observers of a multitude of “them,” singular cells that change human structure – and with it the human psyche – with every discrete (and discreet) bite.

  • 4 Anne-Marie Moulin, Le Dernier langage de la médecine, op. cit., p. 180.

39Turning our gaze now to the speaking subject, Anne-Marie Moulin contends that the birth of immunology constitutes a semantic event, influencing the way man talks about himself and his interactions with others: « Le langage immunologique est entré en résonance avec le système de représentations où les hommes projettent leurs rapports avec leurs semblables au travers des indices biologiques. »4 In view of Metchnikoff’s work, we are surprised to realize that the seemingly monolithic utterance of the “I” rests on one little cell’s (in)digestion, an appetite that “stimulated” a biological and linguistic revolution as it rearticulated the terms of selfhood, giving shape and length to man’s temporally bound, biological existence.

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Notes

1 George Bernard Shaw, The Doctor’s Dilemma, Middlesex, Echo Library, 1906, p. 15.

2 Alfred I. Tauber, Immunity: The Evolution of an Idea, New York, Oxford University Press, 2017, p. 11.

3 Jon Turney, “Beyond Cell Wars,” Aeon, 28 March 2016, consulted 17 July 2020, on-line: https://aeon.co/essays/why-we-should-guard-against-military-notions-of-immunity.

4 Susan Sontag warns of the real consequences wrought by metaphorizing illness, beseeching readers to resist the urges of literary stimulation: “The purpose of my book was to calm the imagination, not to incite it. Not to confer meaning, which is the traditional purpose of literary endeavor, but to deprive something of meaning: to apply that quixotic, highly polemical, ‘against interpretations,’ to the real world this time. To the body.” (Susan Sontag, Illness as Metaphor and AIDS and Its Metaphors, New York, Picador, 1989, p. 102.)

5 Evelyne Fox Keller, Secrets of Life, Secrets of Death: Essays on Language, Gender, and Science, New York, Routledge, 1992, p. 6.

1 Margaret Lock and Vihn-Kim Nguyen, An Anthropology of Biomedicine, Oxford and Malden, MA, Wiley-Blackwell, 2010, p. 236-237 (my emphasis).

2 Evelyn Fox Keller, Making Sense of Life: Explaining Biological Development with Models, Metaphors, and Machines, Cambridge, MA and London, Harvard University Press, 2002, p. 17.

3 John Andrew Mendelsohn, Cultures of Bacteriology: Formation and Transformation of a Science in France and Germany, 1870-1914, PhD, Princeton, 1996, p. 17-18.

4 NIH-U.S. National Library of Medicine, Gallery Dream Anatomy, Der Mensch als Industriepalast” (“Man as Industrial Palace”), Kosmus publishers, Stuttgart, 1926. Chromolithograph, National Library of Medicine, consulted on July 17, 2020, on-line https://www.nlm.nih.gov/exhibition/dreamanatomy/da_g_IV-A-01.html.

5 John Andrew Mendelsohn, “Medicine and the Making of Bodily Inequality in Twentieth-Century Europe”, Heredity and Infection: The History of Disease Transmission, eds. Jean-Paul Gaudillière and Ilana Löwy, London and New York, Routledge, 2001, p. 34. The first instance that I found of le terrain used in a medical context was in a short report on smallpox delivered by the Parisian doctor, Jules Meugy: « Le corps humain est comme un terrain dans lequel les maladies trouvent des conditions plus ou moins avantageuses à leur développement ». Mémoire sur une épidémie de variole, adressé à l’Académie de médicine dans la séance du 4 juillet 1865, Paris, A. Parent, 1865, p. 41 (my emphasis).

6 Arnault Tzanck, « La notion de terrain : Son importance doctrinale », La Presse Médicale, n° 16, 24 février 1934, p. 315.

7 Ibid., p. 317. Evoking the interaction between a pathogen and le terrain, Tzanck points to this perceptive quality: « La réaction n’est donc pas imposée par l’agent externe, mais “déclenchée” par lui. Elle n'est point pathognomonique. Tout se passe comme si c'était le tissu […] qui reconnaissait cette substance provoquant la réaction ».

8 John Andrew Mendelsohn, “Medicine and the Making of Bodily Inequality”, op. cit., p. 24.

1 Timothy Campbell, “Bios, Immunity, Life: The Thought of Roberto Esposito”, Diacritics, vol. 36, n° 2, 2006, p. 2-22.

1 Ed Cohen, A Body Worth Defending, Durham, Duke University Press, 2010, p. 214 (my emphasis).

2 André-Thérèse Chrestien, « De l’immunité et de la susceptibilité morbides, au point de vue de la clinique médicale », Thèse d’agrégation, Montpellier, 1852, p. 2.

3 Chrestien was the first to distinguish between innate and acquired immunity, terms that have survived in the medical lexicon. As the names suggest, one is born with innate immunity whereas one “gains” acquired immunity either “naturally” (when, for example, one contracts an illness and survives, thus “earning” the protection from future contamination) or “artificially” through human intervention, i.e. vaccination.

4 Louis Pasteur, Pasteur : Écrits scientifiques et médicaux, éd. André Pichot, Paris, GF Flammarion, 1994, p. 82n5.

5 Bruno Latour, Pasteur : guerre et paix des microbes suivi de Irréductions, Paris, La Découverte, 2001, p. 196.

6 Louis Pasteur quoted in Bruno Latour, op. cit., p. 34.

7 Caesium and Rubidum are relatively rare elements that were discovered by Robert Bunsen and Gustav Kirchhoff in 1860. They can be found in small quatities in intracellular fluid.

8 Louis Pasteur, Œuvres, éd. Pasteur Vallery-Radot, 7 volumes, Paris, Masson, 1922-1939, VI, p. 315 (my emphasis).

9 Émile Roux, “Jubilé Metchnikoff,” Annales de l’Institut Pasteur, 29, 1915, p. 357.

1 Anne-Marie Moulin, Le Dernier langage de la médecine : Histoire de l’immunologie de Pasteur au Sida, Paris, Presses universitaires de France, 1991, p. 49.

2 See Alfred I. Tauber and Eileen Crist, “The Phagocyte, the Antibody, and Agency in Immunity: Contending turn-of-the-century Approaches”, Singular Selves: Historical Issues and Contemporary Debates in Immunology, eds. Anne-Marie Moulin and Alberto Cambrosio, Paris, Elsevier, 2001, p. 130-35.

3 See Alfred Tauber’s discussion of German reductionism in The Immune Self, Theory or Metaphor?, Cambridge, Cambridge University Press, 1997, p. 53-68.

4 Élie Metchnikoff, Études sur la nature humaine. Essai de philosophie optimiste, Paris, A. Maloine, 1908, p. 312-314.

5 Ibid., p. 352.

6 Metchnikoff, « Sur l’état actuel de la question de l’immunité dans les maladies infectieuses. Conférence Nobel faite à Stockholm le 14 mai 1909 », Les prix Nobel en 1908, Stockholm, Impr. Royal, p. 4.

7 Leon Chernyak and Alfred I. Tauber, Metchnikoff and the Origins of Immunology: From Metaphor to Theory, New York and Oxford, Oxford University Press, 1991, p. xv.

1 Metchnikoff, Études sur la nature humaine, op. cit., p. 33. Again demonstrating the porous boundaries between literature and science, Proust compares himself to the digger wasp in his correspondence with publisher and friend Gaston Gallimard, though with significantly less optimism. See Marcel Proust, “Lettre à Gaston Gallimard” (1922), Correspondance, ed. Philip Kolb, t. 21, Paris, Plon, 1970, p. 494.

2 Kirill Rossiianov makes a compelling argument about race, reading into Metchnikoff’s formulation of the phagocyte an attempt to come to terms with Darwin’s assertion of the “inequality of races”. Metchnikoff’s explanation of the cell as man's most primitive but absolutely vital element takes on Rosseauian overtones in the way it seemingly extols this cellular equivalent of the “nobel savage” (while still asserting the superiority of the more “civilized” elements). However, in Metchnikoff’s case, the discrepancy between the civilized and uncivilized is attributable to biology/evolution and not to exposure to culture. (Kirill Rossiianov, “Taming the Primitive: Elie Metchnikov and His Discovery of Immune Cells”, Osiris, vol. 23, n° 1, 2008, p. 220.)

3 Anne-Marie Moulin, Le Dernier langage de la médecine, op. cit., p. 400.

4 Metchnikoff, Essais optimistes, Paris, A. Maloine, 1907, p. 269.

5 Jean Claude Ameisen, La Sculpture du vivant : Le suicide cellulaire ou la mort créatrice, Paris, Le Seuil, 2003, p. 77-78.

6 Anne-Marie Moulin, Le Dernier langage de la médecine, op. cit., p. 400.

1 These two phenomena were immune tolerance (the lack of a response of the immune system to a “non-self” presence) and autoimmunity (the response of the immune system to the self as if it were other, what Ehrlich had called horror autotoxicus – literally the “horror of self-toxicity” – and had ruled out as an impossibility).

2 In his most recent work, Tauber has revised his understanding of an immune self, replacing the notion of a singular immune identity with the concept of the “holobiont”, an organism comprised of “many species living together in complex immune relationships”, a paradigm that radically alters the notion of a self-same individual. Tauber, The Evolution of an Idea, op. cit., p. x.

3 Barbara Stiegler, Nietzsche et la biologie, Paris, Presses Universitaires de France, 2001, p. 23.

4 Anne-Marie Moulin, Le Dernier langage de la médecine, op. cit., p. 180.

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Loren K. Wolfe, « “Stimulate the Phagocyte”: Contested Terrains and the Birth of Cellular Immunity in turn-of-the-century Paris »Arts et Savoirs [En ligne], 18 | 2022, mis en ligne le 01 octobre 2022, consulté le 18 avril 2024. URL : http://journals.openedition.org/aes/5593 ; DOI : https://doi.org/10.4000/aes.5593

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Loren K. Wolfe

Docteure en langues et littératures romanes, Harvard University

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