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

by Siddhartha Mukherjee

Years later, then, it was nothing less than thrilling—mesmerizing—to watch the cellular revolution unfold in humans. When I first met Emily Whitehead, in a fluorescent-lit corridor outside the auditorium at the University of Pennsylvania, it was as if she had allowed me to enter a portal that linked the future and the past. I trained as an immunologist at first, then a stem cell scientist, and, finally, a cancer biologist before I became a medical oncologist.

Virchow’s accusatory writings did not escape notice. He was marked a liberal—a dangerous, pejorative term in Germany at the time—and placed on watch. When a fulminant populist revolution swept through Europe in 1848, Virchow took to the streets to protest. He founded yet another publication, Medical Reform, in which the confluence of his scientific and political beliefs could be used as a sledgehammer against the state.

Illness was an equalizer; medicine was not designed to discriminate. “Admission to a hospital must be open to every ill person who stands in need of it,” he wrote, “whether he has money or not, whether he is Jewish or heathen.”32 In 1859, he was elected to the Berlin City Council (and eventually, in the 1880s, to the Reichstag). And he began to witness in Germany the resurgence of a malignant form of radical nationalism that would eventually culminate in the Nazi state. The central myth of what would later be termed “Aryan” racial superiority, and a nation dominated by “clean” Volk who were blond, blue eyed, and white skinned, was a pathology already sweeping malevolently through the country.

For generations before Bernard and Cannon, physiologists had described animals as assemblages of machines, sums of dynamic parts. Muscles were motors; the lungs a pair of bellows, the heart a pump. Pulsing, swiveling, pumping; physiology’s emphasis was on movement, on actions, on work. Don’t just stand there, do something. Bernard inverted that logic. “La fixité du milieu intérieur est la condition de la vie libre, indépendante”: the constancy of the interior environment is the condition of free and independent life, Bernard wrote in 1878.23 In shifting physiology’s focus from action to the maintenance of fixity, Bernard changed our conception of how an organism’s body works. A major point of physiological “activity,” paradoxically, was to enable stasis. Don’t just do something, stand there.

This three-layered embryo—ectoderm, mesoderm, endoderm—is the basis of every organ in the human body. The ectoderm will give rise to everything that faces the outer surface of the body: skin, hair, nails, teeth, even the lens of the eye. The endoderm produces everything that faces the inner surface of the body, such as the intestines and the lungs. The mesoderm handles everything in the middle: muscle, bone, blood, heart.

As one writer put it in a 1965 issue of the journal Annals of Internal Medicine, “War has never lavished gifts on humanity; an exception may be made for the impetus and popularization of the use of blood and plasma … attributable to the Spanish Civil War, World War II, and the Korean conflict.”19 Perhaps more than any other intervention, transfusion and banking—cellular therapy—stands as the most significant medical legacy of the war.

In the early eighteenth century, Lady Mary Wortley Montagu, the wife of the British ambassador to Turkey, was herself affected by the pox, her perfect skin left pitted with lesions. In Turkey, she witnessed variolation in practice and, on April 1, 1718, wrote to her lifelong friend Mrs. Sarah Chiswell in wonder: There is a set of old women, who make it their business to perform the operation, every autumn, in the month of September, when the great heat is abated.18 … The old woman comes with a nut-shell full of the matter of the best sort of small-pox, and asks what vein you please to have opened. She immediately rips open that you offer to her, with a large needle (which gives you no more pain than a common scratch) and puts into the vein as much matter as can lie upon the head of her needle, and after that, binds up the little wound with a hollow bit of shell, and in this manner opens four or five veins. Then the fever begins to seize them, and they keep their beds two days, very seldom three. They have very rarely above twenty or thirty in their faces, which never mark, and in eight days time they are as well as before their illness. Where they are wounded, there remains running sores during the distemper, which I don’t doubt is a great relief to it. Every year, thousands undergo this operation, and the French ambassador says pleasantly, that they take the small-pox here by way of diversion, as they take the waters in other countries. There is no example of any one that...

Each such gene rearrangement is also a mutation, although a highly regulated, deliberate kind of mutation in a B cell. A special apparatus fashions the gene rearrangements in an individual B cell, giving each antibody a unique conformational identity, and therefore a unique affinity to bind and hold a particular antigen. The distinctive genetic arrangement in every mature B cell allows it to display a particular receptor on its surface.

It is the acrobatic balance between self-preservation and selflessness—self-renewal and differentiation—that makes the stem cell indispensable for an organism, and thereby enables the homeostasis of tissues such as blood.

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.

Beyond understanding cells in isolation, deciphering the internal laws of cellular citizenship—tolerance, communication, specialization, diversity, boundary-formation, cooperation, niches, ecological relationships—will ultimately result in the birth of a new kind of cellular medicine.