The Gene: An Intimate History

by Siddhartha Mukherjee

The human genome contains about between twenty-one and twenty-three thousand genes that provide the master instructions to build, repair, and maintain humans.

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).

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

Pythagoreans argued that in heredity too a triangular harmony was at work. The mother and the father were two independent sides and the child was the third—the biological hypotenuse to the parents’ two lines. And just as a triangle’s third side could arithmetically be derived from the two other sides using a strict mathematical formula, so was a child derived from the parents’ individual contributions: nature from father and nurture from mother.

I had no idea Pythagoras had helped push theories of genes and heredity

Malthus reasoned, its resource pool would be depleted, and competition between individuals would grow severe. A population’s inherent inclination to expand would be severely counterbalanced by the limitations of resources; its natural wont met by natural want.

In Malthus’s paper, Darwin immediately saw a solution to his quandary. This struggle for survival was the shaping hand. Death was nature’s culler, its grim shaper. “It at once struck me,” he wrote, “that under these circumstances [of natural selection], favourable variations would tend to be preserved and unfavourable ones to be destroyed. The results of this would be the formation of a new species.”

Freaks became norms, and norms became extinct.

How were these gemmular instructions from a father and a mother applied to a developing fetus? Here, Darwin reverted to an old idea: the instructions from the male and female simply met in the embryo and blended together like paints or colors.

Being rediscovered once is proof of a scientist’s prescience. Being rediscovered thrice is an insult. That three papers in the short span of three months in 1900 independently converged on Mendel’s work was a demonstration of the sustained myopia of biologists, who had ignored his work for nearly forty years.

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.

In 1905, still struggling for an alternative, Bateson coined a word of his own. Genetics, he called it: the study of heredity and variation—the word ultimately derived from the Greek genno, “to give birth.”

Bateson was acutely aware of the potential social and political impact of the newborn science. “What will happen when . . . enlightenment actually comes to pass and the facts of heredity are . . . commonly known?” he wrote, with striking prescience, in 1905. “One thing is certain: mankind will begin to interfere; perhaps not in England, but in some country more ready to break with the past and eager for ‘national efficiency.’ . . . Ignorance of the remoter consequences of interference has never long postponed such experiments.”

Crazy to think that the word genetics is only 120 years old, AND it only took that long for us to learn how to mess with genetics so deeplyh with CRISPR

“When power is discovered, man always turns to it,” Bateson wrote darkly. “The science of heredity will soon provide power on a stupendous scale; and in some country, at some time not, perhaps, far distant, that power will be applied to control the composition of a nation. Whether the institution of such control will ultimately be good or bad for that nation, or for humanity at large, is a separate question.” He had preempted the century of the gene.

by manipulating genes, he could manipulate the future.

Little did They know

On July 24, 1912, one year after Galton’s death, the first International Conference on Eugenics opened at the Cecil Hotel in London.

Isnt there a netflix special of pepoe dying here

Two presentations, among all, stood out in their particularly chilling fervor. The first was an enthusiastic and precise exhibit by the Germans endorsing “race hygiene”—a grim premonition of times to come. Alfred Ploetz, a physician, scientist, and ardent proponent of the race-hygiene theory, gave an impassioned talk about launching a racial-cleansing effort in Germany.

In the 1890s, a German embryologist working with sea urchins in Naples, Theodor Boveri, had proposed that genes resided in chromosomes, threadlike filaments that stained blue with aniline, and lived, coiled like springs, in the nucleus of cells (the word chromosome was coined by Boveri’s colleague Wilhelm von Waldeyer-Hartz).

he had linked two disciplines—cell biology and genetics. The gene was not a “purely theoretical unit.” It was a material thing that lived in a particular location, and a particular form, within a cell.

The mutation in the hemophilia gene, which affects the clotting of blood, had likely arisen spontaneously in Queen Victoria at birth. Her eighth child, Leopold, had inherited the gene and died of a brain hemorrhage at age thirty. The gene had also been passed from Victoria to her second daughter, Alice—and then from Alice to her daughter, Alexandra, the czarina of Russia. In the summer of 1904, Alexandra—still an unsuspecting carrier of the gene—gave birth to Alexei, the czarevitch of Russia.

As Alexei grew older, and the hemorrhages more life threatening, Alexandra began to rely on a Russian monk of legendary unctuousness, Grigory Rasputin, who promised to heal the czar-to-be.

The Russian Revolution may not have been about genes, but it was very much about heredity.

Rasputin was poisoned, shot, slashed, bludgeoned, and drowned to death by his rivals on December 30, 1916.

In the early summer of 1918, the royal family was moved to Yekaterinburg and placed under house arrest. On the evening of July 17, 1918, a month shy of Alexei’s fourteenth birthday, a firing squad instigated by the Bolsheviks burst into the czar’s house and assassinated the whole family.

Genetic testing of the bones confirmed that the body was Alexei’s. Had the full genetic sequence of the skeleton been analyzed, the investigators might have found the culprit gene for hemophilia B—the mutation that had crossed one continent and four generations and insinuated itself into a defining political moment of the twentieth century.

Gene heredity affects history

But the real conundrum that heredity solves is much more general: What is the nature of instruction that allows an organism to build a nose—any nose—in the first place?

Dobzhansky could now restate the essential truth of Mendel’s discovery—a gene determines a physical feature—by generalizing that idea across multiple genes and multiple features: a genotype determines a phenotype

But two important modifications to this rule were necessary to complete the scheme. First, Dobzhansky noted, genotypes were not the sole determinants of phenotypes. Obviously, the environment

genotype + environment = phenotype

And second, some genes are activated by external triggers or by random chance.

genotype + environment + triggers + chance = phenotype

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.

But if wild populations with variations in genotype keep interbreeding, Dobzhansky knew, a new species would never be formed: a species, after all, is fundamentally defined by its inability to interbreed with another.

Geographic isolation leads to genetic isolation, and to eventual reproductive isolation.

By the late 1930s, Dobzhansky began to realize that his understanding of genes, variation, and natural selection had ramifications far beyond biology.

In the 1940s, Dobzhansky would attack these questions directly: he would eventually become one of the most strident scientific critics of Nazi eugenics, Soviet collectivization, and European racism. But his studies on wild populations, variation, and natural selection had already provided crucial insights to these questions.

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.

Dobzhansky had sought simplicity—but he had also issued a strident moral warning against the oversimplification of the logic of genetics. Buried in textbooks and scientific papers, these insights would be ignored by powerful political forces that would soon embark on the most perverse forms of human genetic manipulations.

When Muller first tried exposing flies to X-rays, he killed them all. Frustrated, he lowered the dose—and found that he had now sterilized them. Rather than mutants, he had created vast flocks of dead, and then infertile, flies. In the winter of 1926, acting on a whim, he exposed a cohort of flies to an even lower dose of radiation. He mated the x-rayed males with females and watched the maggots emerge in the milk bottles.

It had taken nearly three decades for Morgan and his students to collect about fifty fly mutants in New York. As the botanist noted, with some chagrin, Muller had discovered nearly half that number in a single night.

Like many scientists and social scientists of his era, Muller had been captivated by eugenics since the 1920s. As an undergraduate, he had formed a Biological Society at Columbia University to explore and support “positive eugenics.” But by the late twenties, as he had witnessed the menacing rise of eugenics in the United States, he had begun to reconsider his enthusiasm. The Eugenics Record Office, with its preoccupation with racial purification, and its drive to eliminate immigrants, “deviants,” and “defectives,” struck him as frankly sinister. Its prophets—Davenport, Priddy, and Bell—were weird, pseudoscientific creeps.

But unlike Galton, Muller began to realize that positive eugenics was achievable only in a society that had already achieved radical equality. Eugenics could not be the prelude to equality. Instead, equality had to be the precondition for eugenics. Without equality, eugenics would inevitably falter on the false premise that social ills, such as vagrancy, pauperism, deviance, alcoholism, and feeblemindedness were genetic ills—while, in fact, they merely reflected inequality.

Women such as Carrie Buck weren’t genetic imbeciles; they were poor, illiterate, unhealthy, and powerless—victims of their social lot, not of the genetic lottery.

Without equality, he argued, eugenics would degenerate into yet another mechanism by which the powerful could control the weak.

Its purpose was to enable Rassenhygiene—“racial hygiene.” The Nazis were not the first to use the term: Alfred Ploetz, the German physician and biologist, had coined the phrase as early as 1895

In 1914, Ploetz’s colleague Heinrich Poll, the geneticist, wrote: “Just as the organism ruthlessly sacrifices degenerate cells, just as the surgeon ruthlessly removes a diseased organ, both, in order to save the whole: so higher organic entities, such as the kinship group or the state, should not shy away in excessive anxiety from intervening in personal liberty to prevent the bearers of diseased hereditary traits from continuing to spread harmful genes throughout the generations.”

Thats about as dark as it gets

Several professorships of “race biology” and racial hygiene were established at German universities, and racial science was routinely taught at medical school.

Hitler, imprisoned for leading the Beer Hall Putsch, the failed coup attempt to seize power in Munich, read about Ploetz and race science while jailed in the 1920s and was immediately transfixed.

less than five months after the passage of the Enabling Act, the Nazis enacted the Law for the Prevention of Genetically Diseased Offspring—commonly known as the Sterilization Law.

The outlines of the law were explicitly borrowed from the American eugenics program—if amplified for effect. “Anyone suffering from a hereditary disease can be sterilized by a surgical operation,”

“Once the Court has decided on sterilization,” the law continued, “the operation must be carried out even against the will of the person to be sterilized. . . . Where other measures are insufficient, direct force may be used.”