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

by Siddhartha Mukherjee

Life’s definition, as it stands now, is akin to a menu. It is not one thing but a series of things, a set of behaviors, a series of processes, not a single property. To be living, an organism must have the capacity to reproduce, to grow, to metabolize, to adapt to stimuli, and to maintain its internal milieu.

In a narrow sense, a cell is an autonomous living unit that acts as a decoding machine for a gene. Genes provide instructions—code, if you will—to build proteins, the molecules that perform virtually all the work in a cell. Proteins enable biological reactions, coordinate signals within the cell, form its structural elements, and turn genes on and off to regulate a cell’s identity, metabolism, growth, and death. They are the central functionaries in biology, the molecular machines that enable life.I

How does the self know itself? Because every cell in your body expresses a set of histocompatibility (H2) proteins that are different from the proteins expressed by a stranger’s cells. When a stranger’s skin, or bone marrow, is implanted into your body, your T cells recognize these MHC proteins as foreign—nonself—and reject the invading cells.

It is one of the philosophical enigmas of immunity that the self exists largely in the negative—as holes in the recognition of the foreign. The self is defined, in part, by what is forbidden to attack it. Biologically speaking, the self is demarcated not by what is asserted but by what is invisible: it is what the immune system cannot see. “Tat Twam Asi.” “That [is] what you are.”

We can explain much about the physical, chemical, and biological worlds through evolutionary agglomerations of atomistic units, but those explanations are straining at their leashes. Genes, by themselves, are strikingly incomplete explanations of the complexities and diversities of organisms; we need to add gene-gene interactions and gene-environment interactions to explain organismal physiology and fates. Decades ahead of her time, the geneticist Barbara McClintock called the genome a “sensitive organ of the cell.” The words organ and sensitive reflected ideas totally foreign to geneticists in the fifties and sixties. Arguing against the atomistic gene-by-gene approach favored by geneticists, McClintock proposed, the genome could only be interpreted as a whole—as a “sensitive organ”—that was responsive to its environment. By that same logic, cells, by themselves, are incomplete explanations for organismal complexities. We need to factor in cell-cell interactions, and cell-environment interactions—ushering in holism in cell biology. We possess rudimentary terms for these interactions—ecologies, sociologies, “interactomes”—but still lack models, equations, and mechanisms to understand them. I return, often, to think of disease as a violation of the social compacts between cells.