Credit...Chloe Niclas

Nonfiction

Siddhartha Mukherjee Finds Medical Mystery — and Metaphor — in the Tiny Cell

“The Song of the Cell,” the latest work by the Pulitzer Prize-winning oncologist, recounts our evolving understanding of the body’s smallest structural and functional unit — and its implications for everything from immune therapy and in vitro fertilization to Covid-19.

THE SONG OF THE CELL: An Exploration of Medicine and the New Human, by Siddhartha Mukherjee


In his new book, “The Song of the Cell,” Siddhartha Mukherjee has taken on a subject that is enormous and minuscule at once. Even though cells are typically so tiny that you need a microscope to see them, they also happen to be implicated in almost anything to do with medicine — and therefore almost anything to do with life. Guided by Mukherjee’s granular narration (“As you keep swimming through the cell’s protoplasm …”), I was repeatedly dazzled by his pointillist scenes, the enthusiasm of his explanations, the immediacy of his metaphors. But I also found myself wondering where we were going. What kind of organism might these smaller units add up to? What was the shape of the story he set out to tell?

They’re questions that Mukherjee himself anticipates in the early pages of “The Song of the Cell,” drawing a contrast between the structure of his new book and the arcs of his previous ones. “The Gene” (2016), he says, “was propelled by the quest to decode and decipher the code of life”; his first book, the superb “The Emperor of All Maladies” (2010), which won a Pulitzer Prize, was animated by “the aching quest to find cures for cancer or to prevent it.” This latest effort — with sections on cell biology, on neurons, on immunotherapy, among other topics — “is itself a sum of parts,” Mukherjee writes. “The organization is cellular, if you will.”

But Mukherjee, an oncologist, is too much of a writer to give up on narrative just yet. There may be “no single adversary,” as he puts it, but the book has a protagonist, even if it is protean, and sometimes unreliable: not so much the cell itself but our comprehension of it. Mukherjee whisks us off to the 17th century, when a Dutch cloth merchant named Antonie van Leeuwenhoek trained a simple microscope (which he had been using to examine textile fibers) on a droplet of water, entranced by the wriggling organisms he would call “animalcules.” Less than a decade before, the English scientist Robert Hooke had observed a “great many little boxes” when he put a thin slice of cork under a microscope. (What Hooke saw weren’t actually “cells” per se, but the walls that plant cells build around themselves.) Hooke decided on the name “cell,” from “cella,” the Latin word for “small room.”

Still, it wasn’t until the 19th century that we gained a purchase on what was happening in those small rooms. In 1830s Berlin, the botanist Matthias Schleiden and the zoologist Theodor Schwann laid the foundations for cell theory, positing that both plants and animals had a “common means of formation through cells.” What were those cells doing? A French microscopist named François-Vincent Raspail proposed that the cell was a “laboratory” performing chemical processes that allowed an organism to function. The Prussian physician Rudolf Virchow showed that cells divide and beget new cells. He also offered a cellular theory of disease: “Every pathological disturbance, every therapeutic effect, finds its ultimate explanation only when it’s possible to designate the specific living cellular elements involved.”

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Siddhartha Mukherjee, the author of “The Song of the Cell.”Credit...Deborah Feingold

It’s a potent statement, and Mukherjee says that it’s pinned on a board in his office, a reminder that everything comes down to cells. “As an oncologist, I am, first, a cell biologist,” Mukherjee writes, recalling how a friend was dying of skin cancer because the T cells that attack foreign pathogens couldn’t detect his melanoma, which was “invisible to his immune system.” Immune therapy for cancer patients is cellular therapy. In vitro fertilization? That’s cellular therapy, too. DNA lives in cells, and so genetic engineering is ultimately — you guessed it — cellular therapy.

What this means is that Mukherjee has found an especially roomy subject for his roving intelligence. “I trained as an immunologist at first, then a stem cell scientist and, finally, a cancer biologist before I became a medical oncologist,” he writes, directing the reader to a footnote that mentions his “brief foray into neurobiology.” (A later chapter about blood states that he’s also “a hematologist by training.”) We learn about phagocytosis (the ingestion of a pathogen by an immune cell) and homeostasis (the capacity of a cell to maintain stability and equilibrium); we also learn about the legend of Bali and Vamana, in which arrogance invites comeuppance, and how Mukherjee’s grandmother was so scarred by Partition that she lived with his family but kept in a room to herself. The organization of the book may be cellular, but the overall effect can feel sprawling — like a city that allowed developers to keep building lovely houses while doing little to contain them.

Similarly, some of the writing in “The Song of the Cell” is so lovely that you can get caught up in its music. Mukherjee has an undeniable gift for metaphor, likening an antibody to a “gunslinging sheriff” and a T cell to a “gumshoe detective.” Fatty plaques in the arteries are “precarious mounds of debris alongside highways, accidents waiting to happen.” The essential but underappreciated glial cell was for too long like “a film-star’s assistant stuck perpetually in the shadows of celebrity.” A bacterial protein is so good at making precise changes to the human genome that it’s as if “it can change Verbal to Herbal in the preface to Volume 1 of ‘Samuel Pepys’ Diary’ in a college library containing 80,000 books.”

As for the cell itself, it of course gets some metaphors of its own. The “lone spaceship” of the book’s early chapters becomes a “founder,” and then a “colony,” Mukherjee writes. Blood makes him think of a “cellular civilization”; cancer makes him think of a “cellular ecology.” His subject just gets bigger and bigger and bigger. “Why, might you ask, do the medical mysteries of the Covid-19 pandemic sit at the center of a book on cell biology?” Mukherjee muses. “Because cell biology sits at the center of the medical mysteries.”

If Mukherjee were another kind of storyteller — tidier, if less honest — he could have showcased a more linear narrative, emphasizing how developments in cell research have yielded some truly amazing possibilities. He himself has been collaborating on a project to engineer certain cells in the immune system so that they eat tumors without stirring up an indiscriminate inflammatory response.

But as a practicing physician, he has seen too much suffering and death to succumb to an easy triumphalism. He recalls the “exuberance” of the mid-2000s, when spectacular advances in gene sequencing had made it appear as if “we had unlocked the key to cures for cancer.” Such exuberance turned out to be fleeting; the data from clinical trials were “sobering.”

Many medical mysteries remain unsolved. If the book’s protagonist — our understanding of cell biology — seemed to be riding high again on new advances in immunology, such “self-assuredness” was laid low by the Covid-19 pandemic. Mukherjee presents a string of questions that are still unsettled. “The monotony of answers is humbling, maddening,” he writes. “We don’t know. We don’t know. We don’t know.”


THE SONG OF THE CELL: An Exploration of Medicine and the New Human | By Siddhartha Mukherjee | Illustrated | 473 pp. | Scribner | $32.50

Jennifer Szalai is the nonfiction book critic for The Times. More about Jennifer Szalai

A version of this article appears in print on  , Page 10 of the Sunday Book Review with the headline: Building Blocks. Order Reprints | Today’s Paper | Subscribe

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