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

by Siddhartha Mukherjee

Atomistic claims are the most audacious of all: the scientist is proposing a fundamental reorganization of a world into unitary entities. Atoms. Genes. Cells. You have to think of a cell in a different manner: not as an object under a lens but as a functional site for all physiological chemical reactions, as an organizing unit for all tissues, and as the unifying locus for physiology and pathology. You have to move from a continuous organization of the biological world to a description that involves discontinuous, discrete, autonomous elements that unify that world. Metaphorically, we might say that you have to see past “flesh” (continuous, corporeal, and visible) to imagine “blood” (invisible, corpuscular, and discontinuous).

It is the membrane that defines the boundary; the outer limits of the self. Bodies are bound by a multicellular membrane: the skin. So is the psyche, by another membrane: the self. And so are houses and nations. To define an internal milieu is to define its edge—a place where the inside ends, and the outside begins. Without an edge, there is no self. To be a cell, to exist as cell, it must distinguish itself from its nonself.

In the 1950s and 1960s, medicine and surgery witnessed an explosion of organ-directed therapies: rerouting blood vessels in a heart to bypass a blockage, or replacing a diseased kidney with a transplanted organ. A new universe of drugs emerged—antibiotics, antibodies, chemicals to prevent blood clots or reduce cholesterol. But this is organelle-directed therapy: the replenishment of a functional deficiency in the mitochondrion of a retinal ganglion cell. It represents the culmination of decades of study of cellular anatomy, the dissection of subcellular compartments, and the characterization of their dysfunction in diseased states. It is gene therapy, of course, but also cell therapy in situ—in other words, the restoration of function of a diseased cell in its native anatomical location in the human body.

This much is undeniably true: we’ve thrown open the black box of the cell. To snap the lid shut now might be to foreclose the possibility of a magnificent future. To keep it jammed open without guidelines and rules would be to assume that we’ve reached some tacit global agreement about what is permissible and impermissible in the manipulation of human reproduction and development—which, assuredly, we have not. We used to think about the fundamental features of our cells as our destiny, manifest. We are now beginning to treat these properties as legitimate arenas of scientific annexation—manifest destiny. These debates—the manipulation of reproduction and development, or of embryos to change their genes—are ricocheting around the globe as I write this (and I wrote extensively about the promises as well as the perils of these technologies in The Gene). The arguments won’t be resolved easily, for they impinge not just on the fundamental features of cells, but also on the fundamental features of humans. The only way to find a reasonable answer, or even a compromise, lies in a continuous engagement with evolving debate about the limits of scientific intervention, and the advancing front of cellular technologies. Every human is a stakeholder in this debate. It involves the one, the many, and the “many many.”

Vaccination, more than any other form of medical intervention—more than antibiotics, or heart surgery, or any new drug—changed the face of human health.

And blood? It is a conglomerate of organs, a system of systems. It has built training camps for its armies (lymph nodes), highways and alleys to move its cells (blood vessels). It has citadels and walls that are constantly being surveyed and repaired by its residents (neutrophils and platelets). It has invented a system of identification cards to recognize its citizens and eject intruders (T cells) and an army to guard itself from invaders (B cells). It has evolved language, organization, memory, architecture, subcultures, and self-recognition. A new metaphor comes to mind. Perhaps we might think of it as a cellular civilization.

Our failings, unfortunately, were all too human: a fraying, sclerotic global public health system, the absence of preparedness, misinformation that spread, virus-like, through nations, supply chain issues that made it impossible to procure protective masks and disposable medical suits, strong-men leaders of nations who turned out to be flaccid in their responses to the viral contagion.

The pandemic energized immunology, but it also exposed gaping fissures in our understanding. It provided a necessary dose of humility. I cannot think of a scientific moment that has revealed such deep and fundamental shortcomings in our knowledge of the biology of a system that we had thought we knew. We have learned so much. We have so much left to learn.

Medicine, I wrote, isn’t a doctor with a black bag. It’s a complex web of systems and processes. And systems that we had thought were self-regulating and self-correcting, like a human body in good health, turned out to be exquisitely sensitive to turbulence, like the body during critical illness.