The Gene: An Intimate History

by Siddhartha Mukherjee

our capacity to understand and manipulate human genomes alters our conception of what it means to be “human.”

genes encode chemical messages to build proteins that ultimately enable form and function.

The essence of Darwin’s disruptive genius was his ability to think about nature not as fact—but as process, as progression, as history.

“How small a thought it takes to fill someone’s whole life,” the philosopher Ludwig Wittgenstein wrote.

Natural selection was not operating on organisms but on their units of heredity. A chicken, de Vries realized, was merely an egg’s way of making a better egg.

“Language is not only our servant,” Johannsen wrote, “[but] it may also be our master. It is desirable to create new terminology in all cases where new and revised conceptions are being developed.

In natural language, a word is used to convey an idea. But in scientific language, a word conveys more than an idea—a mechanism, a consequence, a prediction. A scientific noun can launch a thousand questions—and the idea of the “gene” did exactly that.

There is no such thing as perfection, only the relentless, thirsty matching of an organism to its environment. That is the engine that drives evolution.

reproductive incompatibility, ultimately derived from genetic incompatibility, drove the origin of novel species.

it was evident that genetic variation was the norm, not the exception, in nature. American and European eugenicists insisted on artificial selection to promote human “good”—but in nature there was no single “good.” Different populations had widely divergent genotypes, and these diverse genetic types coexisted and even overlapped in the wild. Nature was not as hungry to homogenize genetic variation as human eugenicists had presumed. Indeed, Dobzhansky recognized that natural variation was a vital reservoir for an organism—an asset that far outweighed its liabilities. Without this variation—without deep genetic diversity—an organism might ultimately lose its capacity to evolve.

“Seek simplicity, but distrust it,” Alfred North Whitehead, the mathematician and philosopher, once advised his students.

Genes could, in other words, be transmitted between two organisms without any form of reproduction. They were autonomous units—material units—that carried information.

Messages were not whispered between cells via ethereal pangenes or gemmules. Hereditary messages were transmitted through a molecule, that molecule could exist in a chemical form outside a cell, and it was capable of carrying information from cell to cell, from organism to organism, and from parents to children.

Nazism and Lysenkoism were based on dramatically opposed conceptions of heredity—but the parallels between the two movements are striking. Although Nazi doctrine was unsurpassed in its virulence, both Nazism and Lysenkoism shared a common thread: in both cases, a theory of heredity was used to construct a notion of human identity that, in turn, was contorted to serve a political agenda.

By appropriating the language of genes and inheritance, entire systems of power and statehood were justified and reinforced. By the mid-twentieth century, the gene—or the denial of its existence—had already emerged as a potent political and cultural tool. It had become one of the most dangerous ideas in history.

Junk science props up totalitarian regimes. And totalitarian regimes produce junk science.

Like musicians, like mathematicians—like elite athletes—scientists peak early and dwindle fast. It isn’t creativity that fades, but stamina: science is an endurance sport.

Organisms exist not because of reactions that are possible, but because of reactions that are barely possible. Too much reactivity and we would spontaneously combust. Too little, and we would turn cold and die. Proteins enable these barely possible reactions, allowing us to live on the edges of chemical entropy—skating perilously, but never falling in.

To “see” DNA is to immediately perceive its function as a repository of information. The most important molecule in biology needs no name to be understood.

gene, in short, possessed not just information to encode a protein, but also information about when and where to make that protein.

The combination of regulatory sequences and the protein-encoding sequence defined a gene.

Even though every cell contains the same set of genes—an identical genome—the selective activation or repression of particular subsets of genes allows an individual cell to respond to its environments.

The genome was an active blueprint—capable of deploying selected parts of its code at different times and in different circumstances.

One mechanism of generating variation in nature is mutation—i.e., alterations in the sequence of DNA (an A switched to a T) that may change the structure of a protein and thereby alter its function. Mutations occur when DNA is damaged by chemicals or X-rays, or when the DNA replication enzyme makes a spontaneous error in copying genes.

But a second mechanism of generating genetic diversity exists: genetic information can be swapped between chromosomes. DNA from the maternal chromosome can exchange positions with DNA from the paternal chromosome—potentially generating a gene hybrid of maternal and paternal genes.

Recombination is also a form of “mutation”—except whole chunks of genetic material are sw...

Every cell knew what to “be” because genes told it what to “become” (and where and when to become).

there was no chance, no mystery, no ambiguity—no fate. Cell by cell, an animal was assembled from genetic instructions. Genesis was gene-sis.

A gene is one line in a recipe that specifies an organism. The human genome is the recipe that specifies a human.

The goal was not to restore “normalcy”—but vitality, joy, and function.

It is inscrutable, vulnerable, resilient, adaptable, repetitive, and unique. • It is poised to evolve. It is littered with the debris of its past. • It is designed to survive. • It resembles us.

every genome carries a signature of an individual’s ancestry—but an individual’s racial ancestry predicts little about the person’s genome.

we are culturally or biologically inclined to magnify variations, even if they are minor in the larger scheme of the genome.

Genes cannot tell us how to categorize or comprehend human diversity; environments can, cultures can, geographies can, histories can.

Technologists seek to liberate us from the constraints of our current realities through those transitions. Science defines those constraints, drawing the outer limits of the boundaries of possibility. Our greatest technological innovations thus carry names that claim our prowess over the world: the engine (from ingenium, or “ingenuity”) or the computer (from computare, or “reckoning together”). Our deepest scientific laws, in contrast, are often named after the limits of human knowledge: uncertainty, relativity, incompleteness, impossibility.

Living beings must, of course, obey the fundamental rules of physics and chemistry, but life often exists on the margins and interstices of these laws, bending them to their near-breaking limit.

We live in the loopholes of natural laws, seeking extensions, exceptions, and excuses.

Our genome has negotiated a fragile balance between counterpoised forces, pairing strand with opposing strand, mixing past and future, pitting memory against desire. It is the most human of all things that we possess. Its stewardship may be the ultimate test of knowledge and discernment for our species.