The Song of the Cell: An Exploration of Medicine and the New Human

by Siddhartha Mukherjee

In his 2021 book on ecology and climate, The Nutmeg’s Curse: Parables for a Planet in Crisis, Amitav Ghosh recounts the story of an eminent professor of botany who accompanies a young man from a local village to guide him through a rain forest. The young man is able to identify each of the various plant species. His acumen stuns the professor, who compliments him on his knowledge. But the man is dejected. He “nods and replies with downcast eyes. ‘Yes, I’ve learned the names of all the bushes, but I’ve yet to learn the songs.’ ” Many readers might read the word song as metaphorical. But in my reading, it’s far from a metaphor. What the young man laments is that he hasn’t learned the interconnectedness of the individual inhabitants of the rain forest—their ecology, interdependence—how the forest acts and lives as a whole. A “song” can be both an internal message—a hum—and, equally, an external one: a message sent out from one being to another to signal interconnectedness and cooperativity (songs are often sung together, or to one another). We can name cells, and even systems of cells, but we are yet to learn the songs of cell biology.

Perhaps, as we near the end of this book, we might pause to reflect on one of the most potent philosophical legacies of twentieth-century science—and its limitations. “Atomism” argues that material, informational, and biological objects are built out of unitary substances. Atoms, bytes, genes, I had written in an earlier book. To this we might add: cells. We are built of unitary blocks—extraordinarily diverse in shape, size, and function, but unitary nonetheless. Why? The answers can only be speculative. Because, in biology, it is easier to evolve complex organisms out of unitary blocks by permuting and combining them into different organ systems, enabling each to have a specialized function while retaining features that are common across all cells (metabolism, waste-disposal, protein synthesis). A heart cell, a neuron, a pancreatic cell, and a kidney cell rely on these commonalties: mitochondria to generate energy, a lipid membrane to define its boundaries, ribosomes to synthesize its proteins, the ER and Golgi to export proteins, membrane-spanning pores to let signals in and out, a nucleus to house its genome. And yet, despite the commonalities, they are functionally diverse. A heart cell uses mitochondrial energy to contract and act as a pump. A beta cell in the pancreas uses that energy to synthesize and export the hormone insulin. A kidney cell uses membrane-spanning channels to regulate salt. A neuron uses a different set of membrane channels to send signals that ena...

Epistemic

Universal principles satisfy us—one equation good—because they satisfy our belief in an ordered universe. But why must “order” be so soldierly, so singular, so unifest (as opposed to manifest)? Perhaps one manifesto for the future of cell biology is to integrate “atomism” and “holism.” Multicellularity evolved, again and again, because cells, while retaining their boundaries, found multiple benefits in citizenship. Perhaps we, too, should begin to move from the one to the many. That, more than any other, is the advantage of understanding cellular systems, and, beyond that, cellular ecosystems. We need to know everyone who lives in this building. In January 1902, just as the danse-macabre of German sectarian division, based on the pseudoscience of racial and biological anthropology, was beginning to whir around him, Rudolf Virchow, running from appointment to appointment, missed his footing while stepping off an electric streetcar on Leipziger Street in Berlin. He fell off, injuring his thigh.

Holistic fallacy soft-headed and irresponsibly amalgamated Fallacy Epistemic concern

Virchow continued to work on his understanding of cellular physiology and its converse, cellular pathology, right until his moment of death. The many seminal ideas sparked by his work, and their many offshoots over the ensuing decades, are his lasting legacy and the lessons of this book. His founding tenets of cell biology have expanded into at least ten that I can enumerate, but there will be more as we deepen our understanding of cells:

All cells come from cells.

The first human cell gives rise to all human tissues. Ipso facto, every cell in the human body can be produced, in principle, fr...

Although cells vary widely in their form and function, there are deep physiological similari...

These physiological similarities can be repurposed by cells for specialized functions. An immune cell uses its molecular apparatus for ingestion to eat microbes; a glial cell uses...

Systems of cells with specialized functions, communicating with each other through short- and long-range messages, can achieve powerful physiological functions that individual cells cannot achieve—for example, the healing of wounds, the signaling of metabolic states, sentience, cognition, homeostasis, immunity. The human body functions as a citizenship of cooperating cells. The disintegration of this citizenship tips us from wellness into disease.

! Epistemic brain based learning tie in

Cellular physiology is thus the basis for human physiology, and cellular pathology is the basis for human pathology.

The processes of decay, repair, and rejuvenation in individual organs are idiosyncratic. Specialized cells in some organs are responsible for consistent repair and rejuvenation (blood rejuvenates through human adulthood, albeit at diminished rates), but other organs lack such cells (nerve cells rarely rejuvenate). The balance between injury/dec...

Beyond understanding cells in isolation, deciphering the internal laws of cellular citizenship—tolerance, communication, specialization, diversity, boundary-formation, cooperation, niches, ecological relationships—will ultima...

The capacity to build new humans out of our building blocks—i.e., cells—lies very much within the reach of medicine today; cellular reengineering can ameli...

Cellular engineering has already allowed us to rebuild parts of humans with reengineered cells. As our understanding of this arena grows, new medical and ethical conundrums will arise, intensifying and challenging the basic defin...

These tenets continue to animate, drive—and even surprise—us today. As doctors, we learn these principles. As patients, we live them. As humans entering a new realm of medicine, we will have to learn how to embrace them, challenge them, and incorporate them into our cultures, societies, and selves.

! Epistemic

To argue against human enhancement, Saletan continues, “Sandel needs something deeper: a common foundation for the various norms in sports, arts and parenting. He thinks he has found it in the idea of giftedness. To some degree, being a good parent, athlete or performer is about accepting and cherishing the raw material you’ve been given to work with [italics my own]. Strengthen your body, but respect it. Challenge your child, but love her. Celebrate nature. Don’t try to control everything […] Why should we accept our lot as a gift? Because the loss of such reverence would change our moral landscape.” I used to find Sandel’s argument persuasive—but as the combined forces of genetics and cell engineering extend their reach to touch new depths of the human body and personhood, the “moral landscape” has changed radically: the borderlands between the emancipation from the ravages of disease (extreme short stature, or muscle-wasting cachexia) and the augmentation of human features (increasing height or bulking up muscle) are blurring. Augmentation has become the new emancipation. And the more the borderlands between ailment and enhancement blur, the more easily the “raw” material that Saletan describes is perceived as precisely that: “raw,” and therefore awaiting to be molded into something else—a new kind of human, built anew. “Cooked,” the opposite of “raw,” carries a connotation of augmentation, but also of cheating. But is enhancement cheating? What if it was used to preven...