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

by Siddhartha Mukherjee

The transformation of medicine made possible by our new understanding of cell biology can be broadly divided into four categories. The first is the use of drugs, chemical substances, or physical stimulation to alter the properties of cells—their interactions with one another, their intercommunication, and their behavior. Antibiotics against germs, chemotherapy and immunotherapy for cancer, and the stimulation of neurons with electrodes to modulate nerve cell circuits in the brain fall in this first category. The second is the transfer of cells from body to body (including back into our own bodies), exemplified by blood transfusions, bone marrow transplantation, and in vitro fertilization (IVF). The third is the use of cells to synthesize a substance—insulin or antibodies—that produces a therapeutic effect on an illness. And most recently, there is a fourth category: the genetic modification of cells, followed by transplantation, to create cells, organs, and bodies endowed with new properties.

What is a cell, anyway? 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.*

A cell brings materiality and physicality to a set of genes. A cell enlivens genes.

True knowledge is to be aware of one’s ignorance. —Rudolf Virchow, letter to his father, ca. 1830s

During the sixteenth and seventeenth centuries, most diseases were attributed to miasmas: poisonous vapors emanating from sewage or contaminated air. The miasmas carried particles of decaying matter called miasmata that somehow entered the body and forced it to decay. (A disease such as malaria still carries that history, its name created by joining the Italian mala and aria to form “bad air.”)

He searched for a name for them and finally decided on cells, from cella, a Latin word meaning “small room.” (Hooke had not really seen “cells” but rather the outlines of walls that plant cells build around themselves; perhaps, nestled within them was an actual living cell, but there’s no illustration that proves the point.) “A great many little boxes,” as Hooke imagined them. Unwittingly, he had inaugurated a new conception of living beings, and of humans.

The cell, as it were, is experimenting with physiology, passing molecules in and out, making chemicals and destroying chemicals. It is the laboratory of reactions that enables life.

“The body is a cell state in which every cell is a citizen,” Virchow would write. “Disease is merely the conflict of the citizens of the state brought about by the action of external forces.”

In essence, Virchow had refined Schwann and Schleiden’s cell theory by adding three more crucial tenets to the two founding ones (“All living organisms are composed of one or more cells,” and “The cell is the basic unit of structure and organization in organisms”): 3. All cells come from other cells (Omnis cellula e cellula). 4. Normal physiology is the function of cellular physiology. 5. Disease, the disruption of physiology, is the result of the disrupted physiology of the cell.

It isn’t sufficient to locate a disease in an organ; it’s necessary to understand which cells of the organ are responsible.

It occurs to me, as I write this, how much this framework—germs, cells, risk—still scaffolds the diagnostic art in medicine. Each time I see a patient, I realize, I am probing the cause of his or her disease through three elemental questions. Is it an exogenous agent, such as a bacterium or virus? Is there an endogenous disturbance of cellular physiology? Is it the consequence of a particular risk, be it exposure to some pathogen, a family history, or an environmental toxin?

Germs. Cells. Risk.

Antibiotics, medicines that changed the face of medicine, generally work because they attack something that distinguishes a microbial cell from the host cell. Penicillin kills the bacterial enzymes that synthesize the cell wall, resulting in bacteria with “holes” in their walls. Human cells don’t possess these particular kinds of cell walls, thereby making penicillin a magic bullet against bacterial species that rely on the integrity of their cell walls.

The more we learn about cell biology, the subtler distinctions we uncover, and the more potent antimicrobials we can learn to create.

And now the third branch: archaea. It may be the singularly most startling fact in the history of taxonomy that this full branch of living beings remained undiscovered until about fifty years ago. In the mid-1970s, Carl Woese, a professor of biology at the University of Illinois at Urbana-Champaign, used comparative genetics—the comparison

Mitochondria are found in all cells, but they are particularly densely packed in cells that need the most energy or that regulate energy storage, such as muscle cells, fat cells, and certain brain cells. They are wrapped around the tails of sperm, to provide them enough swimming energy to reach an egg. They divide within the cell, but when it’s the cell’s turn to reproduce, mitochondria are only split between the two daughter cells. In other words, they have no autonomous life; they can live only within cells.

In humans and multicellular organisms, the process for the production of new cells to build organs and tissues is called mitosis—from mitos, the Greek word for “thread.” In contrast, the birth of new cells, sperm, and eggs for the purpose of reproduction—to make a new organism—is called meiosis, from meion, the Greek word for “lessening.”