The Gene: An Intimate History - Siddhartha Mukherjee Page 0,5

that carries our hereditary information and just one code. “That the fundamental aspects of heredity should have turned out to be so extraordinarily simple supports us in the hope that nature may, after all, be entirely approachable,” Thomas Morgan, the influential geneticist, wrote. “Her much-advertised inscrutability has once more been found to be an illusion.”

Our understanding of genes has reached such a level of sophistication and depth that we are no longer studying and altering genes in test tubes, but in their native context in human cells. Genes reside on chromosomes—long, filamentous structures buried within cells that contain tens of thousands of genes linked together in chains.II Humans have forty-six such chromosomes in total—twenty-three from one parent and twenty-three from another. The entire set of genetic instructions carried by an organism is termed a genome (think of the genome as the encyclopedia of all genes, with footnotes, annotations, instructions, and references). The human genome contains about between twenty-one and twenty-three thousand genes that provide the master instructions to build, repair, and maintain humans. Over the last two decades, genetic technologies have advanced so rapidly that we can decipher how several of these genes operate in time and space to enable these complex functions. And we can, on occasion, deliberately alter some of these genes to change their functions, thereby resulting in altered human states, altered physiologies, and changed beings.

This transition—from explanation to manipulation—is precisely what makes the field of genetics resonate far beyond the realms of science. It is one thing to try to understand how genes influence human identity or sexuality or temperament. It is quite another thing to imagine altering identity or sexuality or behavior by altering genes. The former thought might preoccupy professors in departments of psychology, and their colleagues in the neighboring departments of neuroscience. The latter thought, inflected with both promise and peril, should concern us all.

As I write this, organisms endowed with genomes are learning to change the heritable features of organisms endowed with genomes. I mean the following: in just the last four years—between 2012 and 2016—we have invented technologies that allow us to change human genomes intentionally and permanently (although the safety and fidelity of these “genomic engineering” technologies still need to be carefully evaluated). At the same time, the capacity to predict the future fate of an individual from his or her genome has advanced dramatically (although the true predictive capacities of these technologies still remain unknown). We can now “read” human genomes, and we can “write” human genomes in a manner inconceivable just three or four years ago.

It hardly requires an advanced degree in molecular biology, philosophy, or history to note that the convergence of these two events is like a headlong sprint into an abyss. Once we can understand the nature of fate encoded by individual genomes (even if we can predict this in likelihoods rather than in certainties) and once we acquire the technology to intentionally change these likelihoods (even if these technologies are inefficient and cumbersome) our future is fundamentally changed. George Orwell once wrote that whenever a critic uses the word human, he usually renders it meaningless. I doubt that I am overstating the case here: our capacity to understand and manipulate human genomes alters our conception of what it means to be “human.”

The atom provides an organizing principle for modern physics—and it tantalizes us with the prospect of controlling matter and energy. The gene provides an organizing principle for modern biology—and it tantalizes us with the prospect of controlling our bodies and fates. Embedded in the history of the gene is “the quest for eternal youth, the Faustian myth of abrupt reversal of fortune, and our own century’s flirtation with the perfectibility of man.” Embedded, equally, is the desire to decipher our manual of instructions. That is what is at the center of this story.

This book is organized both chronologically and thematically. The overall arc is historical. We begin in Mendel’s pea-flower garden, in an obscure Moravian monastery in 1864, where the “gene” is discovered and then quickly forgotten (the word gene only appears decades later). The story intersects with Darwin’s theory of evolution. The gene entrances English and American reformers, who hope to manipulate human genetics to accelerate human evolution and emancipation. That idea escalates to its macabre zenith in Nazi Germany in the 1940s, where human eugenics is used to justify grotesque experiments, culminating in confinement, sterilization, euthanasia, and mass murder.

A chain of post–World War II discoveries launches a revolution in biology. DNA