In “The Living and Its Milieu,” Georges Canguilhem tells the story of Jakob von Uexküll’s tick. The tick when mature climbs to a high point, such as a branch on a bush. It falls only in response to a single stimulus, the odor of rancid butter, helpfully explained as a component of the sweat of mammals. If there is no corresponding 37-degree centigrade body to latch on to, the tick climbs back up. Apparently von Uexküll kept a tick in his laboratory for eighteen years before providing this stimulus to it, and it was still able to fall on cue, suck blood, and lay eggs when the opportunity was provided. One has to wonder about the number of ticks, and the frequency of testing. Why eighteen years? There is no detail provided about what happened to the other ticks kept “in a state of inanition” beyond 18 years, if there were any.
Within Canguilhem’s essay, the function of the story is to provide a neat illustration of von Uexküll’s concept of the Umwelt, “a milieu centered in relation to that subject of vital values in which the living essentially consists” (Canguilhem 2008, 112). The Umwelt, a subset of the Umgebung or larger geophysical surrounds, is defined by the organism’s needs. So goes the tick, so goes the human—since the subject is the Living, which is a kind of gorgeous glue that sticks every one on the same board: “We must see at the root of this organization of the animal Umwelt a subjectivity analogous to the one we are bound to see at the root of the human Umwelt” (Canguilhem 2008, 112). Are we all out here waiting on our branches for the signal to drop, hoping we’re not in a laboratory with some sadistic fellow with big ideas?
Canguilhem uses the story of the tick as a foil for explaining Kurt Goldstein’s protest against such isolation of stimuli and the treatment of the organism as a machine. From this point of view a tick in a laboratory with nothing to eat for eighteen years is no way to understand life. The experimental situation is the “catastrophic” situation, not the extended debate between organism and environment that is Life. It was fine to bandy about with the odor of rancid butter. But such work of physicochemical analysis was from Goldstein’s point of view, “a chapter in physics. In biology, everything is still to be done. Biology must first hold the living to be a significative being” (Canguilhem 2008, 113). In other words, for Goldstein, you could explain nothing with an isolated stimulus in a laboratory; you’d have to be in the bush with the tick for eighteen years to know what they really did when faced with prolonged inanition, to understand what one would see by following the dialectic that is the organism and its milieu. Finding a better branch, for example.
Canguilhem contrasts von Uexküll and Goldstein with one another but really seems to find within their differences a kind of narrative center for his own conclusions (Wolfe 2015). One can with science propose an absolute universe, a “universal milieu of elements and movements” (here one thinks of the current fashion for yet once again portentously bemoaning the fact that there is no free will because we are all just chemistry). However, Canguilhem notes that the “claim of science to dissolve living beings, which are centers of organization, adaptation, and invention, into the anonymity of the mechanical, physical, and chemical environment must be integral—that is, it must encompass the human living himself,” which leaves one with the impossible question of what science is for and how one could have a science without knowing subjects (Canguilhem 2008, 119). Canguilhem ends the essay writing of the necessity of meaning, which is never universally given and pre-existent but is composed of “values in relation to a need” (120). It is hard to see how he could have narratively arrived at this point—of values and needs, of science as “the work of a humanity rooted in life before being enlightened by knowledge… a fact in the world at the same time as it is a vision of the world”—without the tick (Canguilhem 2008, 120). The story of the tick grounds this vision of what it means to need, and how need orders perception of the world from within a life: how one odor among all the others in a universe of chemicals has such meaning.
Giorgio Agamben also recounts the tale of von Uexküll’s tick in Man and Animal, going so far as to call it “a high point of modern antihumanism” due to the story’s ability to disorient the reader and force a non-human perspective into view (2004, 45). Here too the question of perception and creature subjectivity takes center stage in a philosophical musing via the tick and its strange universe of the odor of rancid butter, mammalian body temperature, and hair and hairlessness (the spot on the skin sought out by the tick through touch). Agamben is particularly taken by the tick in the laboratory, a creature that is understood to only exist as and for a relation (of smell to temperature to nutrition), yet is being kept for eighteen years without these relations. He muses on von Uexküll’s statement that without a living subject, time cannot exist. “What sense does it make,” he asks, “to speak of ‘waiting’ without time and without world?” (Agamben 2004, 48).
Think of this as an update to the odor of rancid butter literature. Why is everyone so interested in the tick? It might be time to put aside the barely masked contempt for chemistry as a chapter of physics, to reclaim it for the everything-that-remains-to-be-done of biology. Let us focus instead on the odor, an instantiation of chemistry pursued in the name of understanding molecular mechanisms whose understanding is nonetheless far more expansive than it is reductive. Taking the odor of rancid butter as our protagonist instead of the tick or the human is to take a perspective on the world that sees relationality as primary to and constitutive of life: or to put it slightly differently, to see organisms as always and only in relation to environments, many of which are composed of and by other organisms.
The odor in question happens to be very good for this purpose and, arguably, provides an even higher peak from which to survey modern anti-humanism, or lower, depending on how you think about it, since we are about to spend some time considering the colon. The odor of rancid butter is more technically known as the molecule butyric acid, also known as a short chain fatty acid (SCFA) because it is composed of a chain of four carbon atoms. Isolated and named at the beginning of the nineteenth century by Michel Chevreul, butyric acid or its salt, butyrate, is widely present in living systems. It is found in larger quantities in butter and parmesan cheese than other foods, while lending kombucha and vomit their particular odiferous qualities. And of course in mammalian sweat, cue tick.
It just so happens that SCFAs in general, and butyric acid in particular, have become the subject of rather intensive research over the last decade or so, because of its important role in organismal physiology and behavior. Butyric acid or butyrate is a product of bacterial carbohydrate metabolism. The role of butyric acid as a semiochemical in the insect world goes well beyond the tick (Davis et al. 2013). Both propionic and butyric acid are produced by bacteria in rotting fruit and are attractive to fruit fly (Drosophila melanogaster) larvae. These fatty acids promote larval fruit fly development and growth by triggering increased feeding behavior—interestingly they are orexigenic for larvae but aversive to adult flies (Depetris-Chauvin et al. 2017). Just as a side note, female fruit flies steer clear of carnivore feces for egg-laying; the phenol produced by bacteria digesting amino acids in high-protein diets confers egg-laying aversion, probably because it is a signal of the presence of bacteria pathogenic to fruit flies and their larvae (Mansourian et al. 2016). In short, “organisms have evolved to exploit microbial volatile organic compounds as behavioral cues” and are especially sensitive to microbial metabolites that “advertise nutrient sources, competitors, predators, mates, and habitat suitability” (Davis et al. 2013, 841). In other words, insects use microbe-generated odors to navigate their way to (or away from) food and habitat, as well as one another.
Mammals also use “metabolites that function as odorants,” which according to the wonderfully-named “fermentation hypothesis” of chemical communication, points to odor as having a symbiotic function, produced by microbes but essential to mammalian signaling (Carthey, Gillings, and Blumstein 2018, 887; Albone and Shirley 1984). Yet following butyric acid’s path, we travel not just between individual animals or insects, or animals and their habitats or foods, but deep inside, to relations that constitute the very insides and outsides that make us think that there are individuals. Inside any given human, for example, this “odor” is roaming through and between entities, and it variably plays a role as substrate, modulator of gene expression, and intercellular signal. Thus, it is far more than an inter-organismal signal even as it underwrites the organism that signals.
In the human gut and particularly in the colon, commensal bacteria metabolize carbohydrates indigestible to their host organisms (such as oat bran) and produce and excrete short chain fatty acids as metabolic byproducts. Butyrate is one of the primary products of bacterial carbohydrate metabolism in the colon (Koh et al. 2016). After its production by bacterial metabolism, it goes on to many diverse fates—it can be excreted in feces or be used immediately as an energy source by the human epithethelial cells lining the colon. These colonic enterocytes are unlike other bodily cells in that they use butyrate as their primary carbon/energy source, a role played by glucose for the majority of other kinds of cells in the body. Butyrate also has unique effects on macrophages patrolling the lamina propria, a thin layer of connective tissue that forms part of the mucosal surfaces of the body; the butyrate suppresses the production of inflammatory molecules by these immune cells (Chang et al. 2014). It does this by being incredibly specific to processes of gene regulation: butyrate binds to the zinc ion in the catalytic site of an enzyme that takes acetyl groups off of the histone proteins that constitute chromatin (Verma et al. 2018). These enzymes, histone deacetylases, are central players in epigenetic gene regulation. Butyrate suppresses their action by blocking the enzyme’s catalytic site, which then has clear physiological effects on a wide range of cells in a wide range of tissues throughout the body, not just in the colon (Verma et al. 2018; Krautkramer et al. 2017). In other words, this microbial metabolite is more than a cue or a signal or a smell, more than an energy source: it is a participant (Landecker and Kelty, forthcoming).
Paradoxically, this tight animal-microbe relation—embodied in the travels of butyrate—contributes to the apparent boundedness of what we call individuals or organisms. Microbial metabolites modulate the very interface of inside and outside that is the gut. The presence of butyrate, itself dependent on fibers such as cellulose and bran in the host diet, tempers the integrity or porosity of the mucosal lining between the alimentary tract and the rest of the body and is therefore being eyed as a preventative for what is more colloquially known as “leaky gut” (Quigley 2016). Moreover, there are indications from experimental biomedicine that a high fiber diet and a microbiota containing butyrate-producing bacteria are also essential to controlling blood brain barrier integrity: germ-free mice have increased blood brain barrier permeability, a condition which is generally regarded as deleterious for brain health (Bourassa et al. 2016; Braniste et al. 2014).
In addition to these roles in energy provision, epigenetic regulation, and barrier integrity, butyrate also functions as a signaling molecule within the body. Generated in the colon and crossing over into the blood stream via the hepatic portal vein, butyrate acts as a ligand to free fatty acid receptors found on the surface of a variety of cell types, for example liver or adipose cells. Other short chain fatty acids, propionate and acetate, also serve various signaling functions, such as being picked up by so-called “chemoreceptors” on kidney cells and setting off cell signaling processes that drive blood pressure regulation, or, in the case of acetate, reaching the brain and affecting appetite (Rajkumar and Pluznick 2017; Sonnenburg and Bäckhed 2016). A shift in the language of olfaction occurs once the viscera are involved and becomes chemoreception, a network of highly specific interactions between bacterial cells, their metabolites, and human cells and tissues. Can we call it an odor at this level of intercellular mediation? Does this genome smell?
Returning to the story of the tick in the philosophy of biology. It seems almost quaint that one could think of this example so freely and as a universal, as an example of how nature works, and an example of how biologist-philosophers clashed over how to interpret such a “fact” observed in a still vaguely naturalist framework. Were we only free to contemplate the tick, and the odor, and the world, without flinching from the scenes in Lyme: The First Epidemic of Climate Change, in which moose bleed to death under the weight of 100,000 ticks infesting every last patch of their skin (Pfeiffer 2018); or without mulling over the fact that butyric acid is commercially useful as a raw material in the manufacture of both flavoring agents and cellulose butyrate, a plastic. Butyric acid is made commercially either by mass microbial fermentation or manufactured via catalyzed air oxidation of butanal (also known as butyraldehyde), which is a derivative of butane, a hydrocarbon that occurs in natural gas and crude oil.
Why would anyone need so much butyric acid that they have to derive it from crude oil? True to form, humans are less likely to sit about contemplating the meaning of the odor of rancid butter and more likely to size up the market for it. Butyric acid or sodium butyrate find a large market in the animal feed industry, where it is added for a variety of reasons, which include making the manufactured feed more palatable to animals (remember, it can be orexigenic), usefully suppressing Salmonella growth in broiler chickens, and contributing to gut integrity in animals (Fernández-Rubio et al. 2009).
As I write this on a plane hurtling many miles above the earth’s surface, the man in the seat next to me opens a bag of Cheetos. I get up and test the range of the smell—it carries at least three rows forward and back. Surreptitiously studying the nutrition facts, I see a serving size is 21 pieces, or 28 grams, in which there are 0.5 grams of fiber: starvation rations for a twenty-first century microbiome. Later, I learn that butyric acid is mobilized as part of the search for “phantom aromas,” smells that are strongly associated with certain tastes, which therefore make food taste of something like cheese to the eater without actually being cheese (Chen 2015). And of course, this mass-mobilization of signals deeply embedded in appetition and satiety are part of the twenty-first century mass-transformation of the microbial-human symbiosis and its collective metabolism, which makes the study of butyrate deeply embedded in concerns over disorders such as diabetes.
The tick in its sterile chamber is now a century or so away. The odor has multiplied, fractured, been mobilized, and become a different set of relations altogether. Its meaning has multiplied to such an extent that it is difficult to contain it in narrative at all. What would Canguilhem do with the odor of rancid butter today? We can no longer trace the ebb and flow of concepts—organisms, milieu—without now also attending to the material chemical transformation of the world by humans and their technical knowledge. Such knowledge remakes the chemical milieu and thus the relations that become the current object of biological knowledge.
Read another piece in this series here.
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