In part, the material composition of the gene had defied identification because biologists had never intercepted genes in their chemical form. Throughout the biological world, genes generally travel vertically—i.e., from parents to children, or from parent cells to daughter cells. The vertical transmission of mutations had allowed Mendel and Morgan to study the action of a gene by analyzing patterns of heredity (e.g., the movement of the white-eyed trait from parent flies to their offspring). But the problem with studying vertical transformation is that the gene never leaves the living organism or cell. When a cell divides, its genetic material divides within it and is partitioned to its daughters. Throughout the process, genes remain biologically visible, but chemically impenetrable—shuttered within the black box of the cell.
Rarely, though, genetic material can cross from one organism to another—not between parent and child, but between two unrelated strangers. This horizontal exchange of genes is called transformation. Even the word signals our astonishment: humans are accustomed to transmitting genetic information only through reproduction—but during transformation, one organism seems to metamorphose into another, like Daphne growing twigs (or rather, the movement of genes transforms the attributes of one organism into the attributes of another; in the genetic version of the fantasy, twig-growing genes must somehow enter Daphne’s genome and enable the ability to extrude bark, wood, xylem, and phloem out of human skin).
Transformation almost never occurs in mammals. But bacteria, which live on the rough edges of the biological world, can exchange genes horizontally (to fathom the strangeness of the event, imagine two friends, one blue eyed and one brown eyed, who go out for an evening stroll—and return with altered eye colors, having casually exchanged genes). The moment of genetic exchange is particularly strange and wonderful. Caught in transit between two organisms, a gene exists momentarily as a pure chemical. A chemist seeking to understand the gene has no more opportune moment to capture the chemical nature of the gene.
Transformation was discovered by an English bacteriologist named Frederick Griffith. In the early 1920s, Griffith, a medical officer at the British Ministry of Health, began to investigate a bacterium named Streptococcus pneumoniae or pneumococcus. The Spanish flu of 1918 had raged through the continent, killing nearly 20 million men and women worldwide and ranking among the deadliest natural disasters in history. Victims of the flu often developed a secondary pneumonia caused by pneumococcus—an illness so rapid and fatal that doctors had termed it the “captain of the men of death.” Pneumococcal pneumonia after influenza infection—the epidemic within the epidemic—was of such concern that the ministry had deployed teams of scientists to study the bacterium and develop a vaccine against it.
Griffith approached the problem by focusing on the microbe: Why was pneumococcus so fatal to animals? Following work performed in Germany by others, he discovered that the bacterium came in two strains. A “smooth” strain possessed a slippery, sugary coat on the cell surface and could escape the immune system with newtlike deftness. The “rough” strain, which lacked this sugary coat, was more susceptible to immune attack. A mouse injected with the smooth strain thus died rapidly of pneumonia. In contrast, mice inoculated with the rough strain mounted an immune response and survived.
Griffith performed an experiment that, unwittingly, launched the molecular biology revolution. First, he killed the virulent, smooth bacteria with heat, then injected the heat-killed bacteria into mice. As expected, the bacterial remnants had no effect on the mice: they were dead and unable to cause an infection. But when he mixed the dead material from the virulent strain with live bacteria of the nonvirulent strain, the mice died rapidly. Griffith autopsied the mice and found that the rough bacteria had changed: they had acquired the smooth coat—the virulence-determining factor—merely by contact with the debris from the dead bacteria. The harmless bacteria had somehow “transformed” into the virulent form.
How could heat-killed bacterial debris—no more than a lukewarm soup of microbial chemicals—have transmitted a genetic trait to a live bacterium by mere contact? Griffith was unsure. At first, he wondered whether the live bacteria had ingested the dead bacteria and thus changed their coats, like a voodoo ritual in which eating the heart of a brave man transmits courage or vitality to another. But once transformed, the bacteria maintained their new coats for several generations—long after any food source would have been exhausted.
The simplest explanation, then, was that genetic information had passed between the two strains in a chemical form. During “transformation,” the gene that governed virulence—producing the smooth coat versus the rough coat—had somehow slipped out of the bacteria into the chemical soup, then out of that soup into live bacteria and become incorporated into the genome of the live bacterium. 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.
Had Griffith publicized this startling result, he would have set all of biology ablaze. In the 1920s, scientists were just beginning to understand living systems in chemical terms. Biology was becoming chemistry. The cell was a beaker of chemicals, biochemists argued, a pouch of compounds bound by a membrane that were reacting to produce a phenomenon called “life.” Griffith’s identification of a chemical capable of carrying hereditary instructions between organisms—the “gene molecule”—would have sparked a thousand speculations and restructured the chemical theory of life.
But Griffith, an unassuming, painfully shy scientist—“this tiny man who . . . barely spoke above a whisper”—could hardly be expected to broadcast the broader relevance or appeal of his results. “Englishmen do everything on principle,” George Bernard Shaw once noted—and the principle that Griffith lived by was utter modesty. He lived alone, in a nondescript apartment near his lab in London, and in a spare, white modernist cottage that he had built for himself in Brighton. Genes might have moved between organisms, but Griffith could not be forced to travel from his lab to his own lectures. To trick him into giving scientific talks, his friends would stuff him into a taxicab and pay a one-way fare to the destination.
In January 1928, after hesitating for months (“God is in no hurry, so why should I be?”), Griffith published his data in the Journal of Hygiene—a scientific journal whose sheer obscurity might have impressed even Mendel. Writing in an abjectly apologetic tone, Griffith seemed genuinely sorry that he had shaken genetics by its roots. His study discussed transformation as a curiosity of microbial biology, but never explicitly mentioned the discovery of a potential chemical basis of heredity. The most important conclusion of the most important biochemical paper of the decade was buried, like a polite cough, under a mound of dense text.
Although Frederick Griffith’s experiment was the most definitive demonstration that the gene was a chemical, other scientists were also circling the idea. In 1920, Hermann Muller, the former student of Thomas Morgan’s, moved from New York to Texas to continue studying fly genetics. Like Morgan, Muller hoped to use mutants to understand heredity. But naturally arising mutants—the bread and butter of fruit fly geneticists—were far too rare. The white-eyed or sable-bodied flies that Morgan and his students had discovered in New York had been fished out laboriously by hunting through massive flocks of insects over thirty years. Tired of mutant hunting, Muller wondered if he could accelerate the production of mutants—perhaps by exposing flies to heat or light or higher bursts of energy.
In theory, this sounded simple; in practice, it was tricky. 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 c
reated 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.
Even a cursory look confirmed a striking result: the newly born flies had accumulated mutations—dozens of them, perhaps hundreds. It was late at night, and the only person to receive the breaking news was a lone botanist working on the floor below. Each time Muller found a new mutant, he shouted down from the window, “I got another.” 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.
Muller was catapulted into international fame by his discovery. The effect of radiation on the mutation rate in flies had two immediate implications. First, genes had to be made of matter. Radiation, after all, is merely energy. Frederick Griffith had made genes move between organisms. Muller had altered genes using energy. A gene, whatever it was, was capable of motion, transmission, and of energy-induced change—properties generally associated with chemical matter.
But more than the material nature of the gene, it was the sheer malleability of the genome—that X-rays could make such Silly Putty of genes—that stunned scientists. Even Darwin, among the strongest original proponents of the fundamental mutability of nature, would have found this rate of mutation surprising. In Darwin’s scheme, the rate of change of an organism was generally fixed, while the rate of natural selection could be amplified to accelerate evolution or dampened to decelerate it. Muller’s experiments demonstrated that heredity could be manipulated quite easily: the mutation rate was itself quite mutable. “There is no permanent status quo in nature,” Muller later wrote. “All is a process of adjustment and readjustment, or else eventual failure.” By altering mutation rates and selecting variants in conjunction, Muller imagined he could possibly push the evolutionary cycle into hyperdrive, even creating entirely new species and subspecies in his laboratory—acting like the lord of his flies.
Muller also realized that his experiment had broad implications for human eugenics. If fly genes could be altered with such modest doses of radiation, then could the alteration of human genes be far behind? If genetic alterations could be “induced artificially,” he wrote, then heredity could no longer be considered the unique privilege of an “unreachable god playing pranks on us.”
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.
As Muller thought about the future of eugenics and the possibility of altering human genomes, he wondered whether Galton and his collaborators had made a fundamental conceptual error. Like Galton and Pearson, Muller sympathized with the desire to use genetics to alleviate suffering. 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. The Galtonians had been convinced that eugenics would ultimately generate radical equality—transforming the weak into the powerful. Muller turned that reasoning on its head. Without equality, he argued, eugenics would degenerate into yet another mechanism by which the powerful could control the weak.
While Hermann Muller’s scientific work was ascending to its zenith in Texas, his personal life was falling apart. His marriage faltered and failed. His rivalry with Bridges and Sturtevant, his former lab partners from Columbia University, reached a brittle end point, and his relationship with Morgan, never warm, devolved into icy hostility.
Muller was also hounded for his political proclivities. In New York, he had joined several socialist groups, edited newspapers, recruited students, and befriended the novelist and social activist Theodore Dreiser. In Texas, the rising star of genetics began to edit an underground socialist newspaper, The Spark (after Lenin’s Iskra), which promoted civil rights for African-Americans, voting rights for women, the education of immigrants, and collective insurance for workers—hardly radical agendas by contemporary standards, but enough to inflame his colleagues and irk the administration. The FBI launched an investigation into his activities. Newspapers referred to him as a subversive, a commie, a Red nut, a Soviet sympathizer, a freak.
Isolated, embittered, increasingly paranoid and depressed, Muller disappeared from his lab one morning and could not be found in his classroom. A search party of graduate students found him hours later, wandering in the woods in the outskirts of Austin. He was walking in a daze, his clothes wrinkled from the drizzle of rain, his face splattered with mud, his shins scratched. He had swallowed a roll of barbiturates in an attempt to commit suicide, but had slept them off by a tree. The next morning, he returned sheepishly to his class.
The suicide attempt was unsuccessful, but it was symptomatic of his malaise. Muller was sick of America—its dirty science, ugly politics, and selfish society. He wanted to escape to a place where he could meld science and socialism more easily. Radical genetic interventions could only be imagined in radically egalitarian societies. In Berlin, he knew, an ambitious liberal democracy with socialist leanings was shedding the husk of its past and guiding the birth of a new republic in the thirties. It was the “newest city” of the world, Twain had written—a place where scientists, writers, philosophers, and intellectuals were gathering in cafés and salons to forge a free and futuristic society. If the full potential of the modern science of genetics was to be unleashed, Muller thought, it would be in Berlin.
In the winter of 1932, Muller packed his bags, shipped off several hundred strains of flies, ten thousand glass tubes, a thousand glass bottles, one microscope, two bicycles, and a ’32 Ford—and left for the Kaiser Wilhelm Institute in Berlin. He had no inkling that his adopted city would, indeed, witness the unleashing of the new science of genetics, but in its most grisly form in history.
Lebensunwertes Leben (Lives Unworthy of Living)
He who is bodily and mentally not sound and deserving may not perpetuate this misfortune in the bodies of his children. The völkische [people’s] state has to perform the most gigantic rearing-task here. One day, however, it will appear as a deed greater than the most victorious wars of our present bourgeois era.
—Hitler’s order for the Aktion T4
He wanted to be God . . . to create a new race.
—Auschwitz prisoner on Josef Mengele’s goals
A hereditarily ill person costs 50,000 reichsmarks on average up to the age of sixty.
—Warning to high school students in a Nazi-era German biology textbook
Nazism, the biologist Fritz Lenz once said, is nothing more than “applied biology.”I
In the spring of 1933, as Hermann Muller began his work at the Kaiser Wilhelm Institute in Berlin, he watched Nazi “applied biology” swing into action. In January that year, Adolf Hitler, the Führer of the National Socialist German Workers’ Party, was appointed the chancellor of Germany. In March, the German parliament endorsed the Enabling Act, granting Hitler unprecedented power to enact laws without parliamentary in
volvement. Jubilant Nazi paramilitary troops marched through the streets of Berlin with firelit torches, hailing their victory.
“Applied biology,” as the Nazis understood it, was really applied genetics. 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 (recall his sinister, impassioned speech at the International Conference on Eugenics in London in 1912). “Racial hygiene,” as Ploetz described it, was the genetic cleansing of the race, just as personal hygiene was the physical cleaning of the self. And just as personal hygiene routinely purged debris and excrement from the body, racial hygiene eliminated genetic detritus, thereby resulting in the creation of a healthier and purer race.II 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.”
Ploetz and Poll looked to British and American eugenicists such as Galton, Priddy, and Davenport as pioneers of this new “science.” The Virginia State Colony for Epileptics and Feebleminded was an ideal experiment in genetic cleansing, they noted. By the early 1920s, as women like Carrie Buck were being identified and carted off to eugenic camps in America, German eugenicists were expanding their own efforts to create a state-sponsored program to confine, sterilize, or eradicate “genetically defective” men and women. Several professorships of “race biology” and racial hygiene were established at German universities, and racial science was routinely taught at medical school. The academic hub of “race science” was the Kaiser Wilhelm Institute for Anthropology, Human Heredity and Eugenics—a mere stone’s throw away from Muller’s new lab in Berlin.