The Gene: An Intimate History

by Siddhartha Mukherjee

In 1883, one year after Charles Darwin’s death, Darwin’s cousin Francis Galton published a provocative book—Inquiries into Human Faculty and Its Development—in which he laid out a strategic plan for the improvement of the human race. Galton’s idea was simple: he would mimic the mechanism of natural selection. If nature could achieve such remarkable effects on animal populations through survival and selection, Galton imagined accelerating the process of refining humans via human intervention. The selective breeding of the strongest, smartest, “fittest” humans—unnatural selection—Galton imagined, could achieve over just a few decades what nature had been attempting for eons.

Adolphe Quetelet—an astronomer-turned-biologist—had begun to systematically measure human features and analyze them using statistical methods. Quetelet’s approach was rigorous and comprehensive. “Man is born, grows up and dies according to certain laws that have never been studied,” Quetelet wrote. He tabulated the chest breadth and height of 5,738 soldiers to demonstrate that chest size and height were distributed along smooth, continuous, bell-shaped curves. Indeed, wherever Quetelet looked, he found a recurrent pattern: human features—even behaviors—were distributed in bell-shaped curves.

Galton coined the memorable phrase nature versus nurture

I have always maintained that, excepting fools, men did not differ much in intellect, only in zeal and hard work.”

By the late 1930s, Dobzhansky began to realize that his understanding of genes, variation, and natural selection had ramifications far beyond biology. The bloody revolution of 1917 that had swept through Russia attempted to erase all individual distinctions to prioritize a collective good. In contrast, a monstrous form of racism that was rising in Europe exaggerated and demonized individual distinctions. In both cases, Dobzhansky noted, the fundamental questions at stake were biological. What defines an individual? How does variation contribute to individuality? What is “good” for a species?

genetic variation was the norm, not the exception, in nature.

in nature there was no single “good.”

Nature was not as hungry to homogenize genetic variation as human eugenicists had presumed.

Of the several million variants of biological molecules in the human body (enzymes, receptors, hormones—and so forth), only about 250—0.025 percent—are therapeutically modulated by our current pharmacopeia. If human physiology is visualized as a vast global telephone network with interacting nodes and networks, then our current medicinal chemistry touches only a fraction of a fraction of its complexity;

Normal cells could acquire these cancer-causing mutations through four mechanisms. The mutations could be caused by environmental insults, such as tobacco smoke, ultraviolet light, or X-rays—agents that attack DNA and change its chemical structure. Mutations could arise from spontaneous errors during cell division (every time DNA is replicated in a cell, there’s a minor chance that the copying process generates an error—an A switched to a T, G, or C, say). Mutant cancer genes could be inherited from parents, thereby causing hereditary cancer syndromes such as retinoblastoma and breast cancer that coursed through families. Or the genes could be carried into the cells via viruses, the professional gene carriers and gene swappers of the microbial world. In all four cases, the result converged on the same pathological process: the inappropriate activation or inactivation of genetic pathways that controlled growth, causing the malignant, dysregulated cellular division that was characteristic of cancer.

It encodes about 20,687 genes in total—only 1,796 more than worms, 12,000 fewer than corn, and 25,000 fewer genes than rice or wheat. The difference between “human” and “breakfast cereal” is not a matter of gene numbers, but of the sophistication of gene networks. It is not what we have; it is how we use it.

Mitochondrial Eve.

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

the red marks tended to cluster toward the right, while the unmarked men tended to cluster to the left. Gay men tended to have gay uncles—but only on the maternal side. The more Hamer hunted up and down the family trees for gay relatives—a “gay Roots project,” as he called it—the more the trend intensified. Maternal cousins had higher rates of concordance—but not paternal cousins. Maternal cousins through aunts tended to have higher concordance than any other cousins.

personalities along four archetypal dimensions: novelty seeking (impulsive versus cautious), reward dependent (warm versus detached), risk avoidant (anxious versus calm), and persistent (loyal versus fickle).

First, most genes, as Richard Dawkins describes them, are not “blueprints” but “recipes.” They do not specify parts, but processes; they are formulas for forms. If you change a blueprint, the final product is changed in a perfectly predictable manner: eliminate a widget specified in the plan, and you get a machine with a missing widget. But the alteration of a recipe or formula does not change the product in a predictable manner: if you quadruple the amount of butter in a cake, the eventual effect is more complicated than just a quadruply buttered cake (try it; the whole thing collapses in an oily mess).

In 1991, having moved to the Wisconsin Regional Primate Center, Thomson began to derive ES cells from monkeys. He plucked a six-day-old embryo from a pregnant rhesus monkey,

Insan kok hucre

Normalcy is the antithesis of evolution.