What We Talk About When We Talk About the Interstitium

Anatomical drawing of a human figure with dissected torso, 1927. Exposition d’art Medico-Historique, via Wikimedia Commons. Licensed under CC BY 4.0. Like many doctors I know, I found myself being peppered with questions from friends and patients—some genuinely curious, others more finger-wagging—after The New York Times Magazine published a long piece in the spring about the “discovery of a third circulatory system.” Recent experiments had shown that foreign materials such as tattoo ink or chemical tracers could migrate into what the magazine described as “hidden pathways” throughout the body—routes that did not correspond with either of the conventionally accepted networks that Western medicine has mapped and taught for centuries. “The implications of a new circulatory system,” the writer claimed, “are potentially enormous.” The article was referring to the interstitium, a catchall term for the mostly cell-less, latticed network of proteins and fluids that surrounds our organs and tissues. This system was already known to the sixteenth-century Flemish anatomist Andreas Vesalius, whose illustration collections number among the first mass-produced medical textbooks, and to anyone who has ever looked at the iridescent cobwebs that split as one carves a cooked turkey. But unlike the other two kinds of classically recognized circulation—the vasculature and lymphatic systems—the interstitium and its fluid dynamics go minimally discussed in Western medicine, whether in the formal training of physicians or at the level of popular science. (Think of an anatomical dummy in a grade-school classroom, its extractable eyes, heart, liver all fitting neatly on their hooks and pegs like chocolates inside an Advent calendar.) Acupuncture points and meridians from The Golden Mirror of Medicine (1742), by Wu Chien, via Wikimedia Commons. Licensed under CC BY 4.0. Other current and historical medical practices have postulated wild lines of flight across the body, far more elaborate than the Hippocratic humors. Traditional Chinese medicine envisioned the san jiao as a network of waterways that could be manipulated by acupuncture, not unlike the 114 chakras and 72,000 nadis (energy pathways) of Ayurveda. Ancient Egyptians conceived of metu—networks of vessels, connecting disparate organs. As one papyrus from the sixteenth century B.C.E. has it, “When the Heart feels an aversion, behold it is the Bitterness of the Heart because of Inflammation in the Anus.” By contrast, contemporary Western medicine, which I practice as an internist, focuses mainly on microscopic cells and macroscopic organ systems. We tend to regard anything in the body that is neither cell nor organ as part of a sumptuous and mysterious background, like the velvety smog behind a Rembrandt self-portrait. In that sense, recent studies, per the Times essay, “broke accepted anatomic boundaries.” One showed, for example, that when cadavers were injected at traditional acupuncture points and then given chest compressions, the injected tracers appeared to march from the periphery toward the heart—seemingly traveling not via blood vessels or lymphatic networks but rather along the gel matrix of the interstitium’s extracellular space. Reactions to this purported breakthrough fell along familiar lines: “Did Science Finally Find the Meridians?” one essay on Substack asked, going on to muse about the way Western medicine has long ignored the practices of its Eastern counterparts. On the other hand, Science-Based Medicine, a website devoted to debunking what it deems quackery, published a post called “NYT Epic Fail on Acupuncture,” calling out the “rank pseudoscience” afoot in the idea that interstitial space validates ancient beliefs about hidden channels of flow. My dual loyalties twinge in these kinds of dustups. I’m a doctor, but also a poet. When I read the Times piece, I was waiting for a Zoom meeting to start, about how best to bring poetry to interested medical students. I have also been a patient, and the mother, wife, or daughter of a patient; narratives about the chauvinism of doctors, slow to admit error or blind spot, rhyme with many of those experiences, as well as my own moments of arrogance and overcertainty. And yet I still find my profession’s habitual scrupulosity, its reluctance to change too quickly, to be one of its most irreplaceable merits, a fixity in an unsteady world. *** Any education in looking starts by learning to discriminate edges and objects, to rank what we see in terms of importance, urgency, proximity. Then, as we progress in our learning, we attempt to train ourselves out of such distinctions, to question such hierarchies, to appreciate the fullness of an image as much as its central or foregrounded subject. Édouard Manet, Olympia, 1863. Photograph by Jean-Pierre Dalbéra, via Wikimedia Commons. Licensed under CC BY 2.0. We begin to recognize, as Virginia Woolf did in her essay “The Elizabethan Lumber-Room,” that the particular charm of an attic (or, as she suggests, of an era), is not merely those objects of “priceless value” but that they are indiscriminately piled up alongside those of “complete worthlessness”—that “ivory, old iron, broken pots, urns, unicorns’ horns” jostle for the viewer’s attention. Or to discover that the most interesting thing about Manet’s Olympia may not be the central nude but the way she is illuminated—with what Michel Foucault called the “perpendicular light” that seems to radiate from “the space in front of the canvas,” as if “our gaze upon the Olympia is a lantern.” That negative space outside the canvas becomes part of the composition as a whole. Amateurs can still find specific step-by-step instructions on how to draw—which is to say, more or less, how to see—Popeye, for example, or a horse. But serious students know that what they’re after is not a discrete number of objects to depict on command so much as the techniques—cognitive, physical, emotional—that will allow them to apprehend, and make apprehensible, a range of effects. The interstitium, as conventionally conceived, is the body’s negative space—the white surrounding the text of a poem, the rest within a phrase of music. Made of a collagen scaffold, hyaluronic matrix, and bloodless fluid, it has few cells and so has relatively little of what we think of as life’s hallmarks—the unfurling of genetic materials; cellular reproduction, then entropy and death. The interstitium seems plotless, an entity that, as Auden claimed of poetry, “makes nothing happen,” a gooey scaffold girding the “real” life occurring around it. American medical training underwent several major revisions in the twentieth century, one of which entailed a shift toward learning by organ systems, one organ grouping at a time. This overturned the older method of sequentially learning different disciplinary approaches—how the anatomist apprehends the body, how the physiologist does, the biochemist, the pharmacologist. Organ system–based learning makes a great deal of sense: you may as well learn how to treat illnesses of the heart while you’re learning how blood and electricity move through it, or how the arteries will react to the cardiac medication you might prescribe. Placenta with amniotic sac, from Icones uteri humani observationibus illustratae (1759) by Johann Georg Roederer, via Wikimedia Commons. Licensed under CC BY 4.0. But the organ-system framework has numerous shortcomings. I know next to nothing, for example, about teeth—and not only because insurance markets put them in a largely separate budgetary category (eyes, too). They aren’t actually bones (and so don’t fit into the musculoskeletal system) and stubbornly resist being studied alongside the digestive system, since their makeup has little to do with the slime-lined absorption and secretion systems that unify our various tubes. Or take the placenta, which defies our ordinary definition of an organ—being, as Sophie Lewis argues polemically in Full Surrogacy Now, a “ghastly fluke” that neither has nor respects boundaries, eroding into vessels in ways that occasionally kill its host. To see human anatomy in its complexity, we must unsee the monadic, isolationist fiction of the well-wrought organ, much as Arnold Schoenberg challenged the normative supremacy of sound over silence and Ruth Asawa made air as integral to her sculptures as their wire forms. One of my favorite squabbles in the history of poetry arose between Denise Levertov and Robert Creeley in 1990, when the former criticized the latter for suggesting that William Carlos Williams intended, in public readings, to deliver his line breaks as significant pauses. For Levertov, these halts were simply the unfortunate by-product of Williams’s neurological struggles following a series of strokes. Creeley countered that, whatever the cause, Williams’s halting patter improved his reading. The strokes had “necessitated or, more to the point, discovered” powers that had been present—but largely overlooked—in the poems. The inability to read smoothly—to properly privilege semantic sense—revived the poems’ crucial animating magic: their negative space, the wordless intervals when language wasn’t “happening.” As I take it, Levertov didn’t want the inadvertent to be misread as activity, or for a lapse to be understood as a choice. A poem is the sum of the poet’s selected words and what those words accomplish; like organs, they are busy and pluripotent, absorbing and secreting all kinds of nourishment, toxicity, and elaboration. The poem has little to do with whatever contingencies accrete around it. For Creeley, a playing up of the interstitial was all to the good. Foregrounding the surroundings—troubling, that is, the very nature of “foreground”—is one of the special features of art. In medicine, applying a similar dialectic reconfigures how we see centrality versus periphery. “Decellularization techniques” subject whole cadavers, or parts of them, to a series of enzymatic and pH-altering baths that gradually strip away, as the name suggests, any sort of cell. What’s left is not, of course, nothing. The translucent drapery of the interstitium’s fibers and proteins is eerie and beautiful: an alabaster reliquary for the heart, an openwork scaffold for the liver that resembles a coral sea fan. It can be hard to reconcile these meshy, evanescent structures with our notions of the corporeal self. Yet this network of negative space is as much us as a drop of spit or sweat or semen. We are generally uncomfortable with a body that is useless or passive. It’s exciting to discover—as scientists have recently done—that the appendix is not actually “vestigial” but rather a crucial harbor of the gut microbiome. A certain strain of feminist pop-science loves to note that the uterus can summon one hundred pounds of force per contraction and that it can alter its environment to encourage or deter reproduction, as though such facts somehow shore up the argument for women’s reproductive rights. It feels good to imbue each part of the body with powers, activities, even intentions. I’m not immune to this mindset, but I also see how it creates its own voracious momentum—a need to assign to each cluster of cells a kind of tactical vigor or productivity. This eagerness to find usefulness everywhere makes me reflexively hesitant to embrace some of the new research on the interstitium. Numerous studies, for example, on “sham” acupuncture—needles inserted in unconventional places, or that sit atop rather than penetrate the skin—have yielded results comparable to traditional practice, undermining the idea that the latter affects the interstitium in some special way. It might—but I’m not sure we know, and our wanting can so easily run ahead of our knowing. Would it be so terrible, I wonder, if the interstitium turned out to be a site of minimal activity? A true limbo, a pause, a white space, yet still inextricably part of us, just as much as that high-achieving heart or brain or uterus. That is to say: Surely many wondrous biological discoveries await us as we learn about what goes on in this beautiful proteinaceous goop. But also, some degree of uselessness would be just fine, some welcome silence amid the noise. Laura Kolbe is a physician, medical ethicist, and writer. Her debut poetry collection, Little Pharma, won the Agnes Lynch Starrett Poetry Prize in 2021. Her next book, The Decadent Movement, will be published by the University of Pittsburgh this fall. Last / Next Article Share