On the Origins of Modern Biology and the Fantastic: Part 10—Ray Bradbury and Mechanisms of Regulation

“They blended religion and art and science, because, at base, science is no more than an investigation of a miracle we can never explain, and art is an interpretation of that miracle. They can never let science crush the aesthetic and the beautiful.” —Spender, “—And The Moon Be Still As Bright” from The Martian Chronicles by Ray Bradbury

The Martian Chronicles, published in 1950, represented something unique and different in science fiction. At the optimistic opening of the space age, if offered a perspective on the lie that the promise of a new frontier offers, as though by traveling to Mars we assumed we would leave behind our weakness and bigotry. It’s Bradbury up and down, sacrificing scientific rigor in favor of poetic metaphor; one part awe, one part sadness, three parts nostalgia. It brought a literary perspective to science fiction, tackling themes of loneliness, regret, and the inevitable loss of innocence. Bradbury sought the deeper meanings in the established mechanics of science fiction and his stories encompassed an added layer of complexity that would have a profound impact on an up-and-coming generation of writers.

Science fiction, up until this point, had completed its first revolution. From its early modern roots in the technologically-focused Verne and the socially conscious Wells, it proceeded through its growing pains with two at first disparate traditions, with the more literary-minded English modernist traditions of Stapledon and Aldous Huxley on one hand, and the whizz-bang American pulp adventure tales of Burroughs during the era of Gernsback on the other. But the devastation of both World Wars had Europe reeling, and left the codification to the American editor Campbell, under whom the politics of Heinlein, the logic of Asimov, and the technical literacy of Clarke would carry the field from its adolescence into its optimistic young adulthood. By the 1950s, thanks in no small part to World War II, America had pulled out of the Great Depression and the Space Age was dawning, and as a result, science fiction was making its way out of the magazines into the public consciousness with radio, comic strips, and cinema, and an entirely new kind of science fiction began to emerge, one free of Campbell’s restrictive definitions.

Biology, too, in a similar time span, had emerged from its own revolution, from the revelations of Darwin’s expansive Theory of Evolution and Mendel’s meticulous laws of heredity establishing the foundation of two different traditions of the very large and the very small. Searching for their own codifying principles, the first came from Julian Huxley in marrying the very large to the very small with his Modern Synthesis, and which found its underlying molecular principles in Crick’s Central Dogma in the ‘50s and ‘60s. The basic toolkit of biological interrogation had been established and the field was poised to uncover the deeper layers of complexity that governed all life on earth—or as Monod put it, the “second secret of life.”

Ray Douglas Bradbury was always desperate for his life to have meaning beyond his mortality. Born in 1920 in Waukegan, Illinois, he was a sensitive and precocious child of the Great Depression, who became aware of death at a young age with multiple losses occurring within the family during his early life. An outsider in a stoic family, Bradbury developed an early affinity for the macabre and fantastic, which was indulged by his mother’s love of Universal horror movies and his aunt Neva, who gave him Baum’s Wizard of Oz books, fairy tales, and Burroughs, alongside Bradbury’s own obsessions with Buck Rogers comics, magic, and dinosaurs. When he was fourteen, his father—perpetually unemployed and with a bad case of wanderlust which periodically moved them back and forth between Illinois and Arizona—permanently moved the family to Los Angeles for work. Bradbury would frequently haunt movie studios for autographs, and once he graduated high school, sold newspapers for movie tickets and bus fare (never learning to drive after seeing a horrific accident in L.A.). But all the time he was writing, seeing it as a path to the same immortality his literary heroes had achieved. At first he imitated—Doyle, Wodehouse, Henry James, Lovecraft, and Poe—but his writing became more focused after he’d joined the regional chapter of the Los Angeles Science Fiction Society where he met Heinlein, who was very encouraging. In 1941, when Bradbury was 21, he had his first breakthrough, selling his first story, “Pendulum,” to a paying market.

In the world of science, Monod’s own breakthrough was to give a larger meaning to the Central Dogma. Yes, genes were transcribed into messenger RNA, which was translated into proteins in the cell, but every cell in an organism contains the same genetic blueprints, while the protein compositions are are unique. Therefore, understanding how genes and proteins were regulated was the crucial next step, and the first hint would come once again from Cambridge’s Cavendish Laboratory. While DNA, a relatively simple molecule, gave up its secrets to X-rays rather easily, larger molecules proved elusive. Max Perutz, an Austrian with an interest in crystals, was recruited to the Cavendish following his work on glaciers with the goal of marrying structure to function, and so he focused on the structure of horse hemoglobin to determine how it transports oxygen in the blood. Perutz was a fastidious scientist, but traditional Fourier calculations, used to determine the angle of reflection of the X-rays off of atoms (hundreds done by hand for each spot) proved impossible. The structure was too complex. Then, in 1951 when a nervous Perutz gave a talk to the group titled, “What Mad Pursuit,” Crick announced Perutz was going about it was all wrong: He needed a reference point to give the images meaning.

Back in the U.S., after the bombing of Pearl Harbor, Bradbury became nervous about losing his shot at immortality if drafted (his eyesight ultimately disqualified him), so he vowed to start writing one short story a week—a pace he kept up much of his life. At first, his derivative early style earned few sales, but with focused effort, his prose went from purple to poetic, and in 1942 he wrote what he considered his first great story, “The Lake,” which dealt with familiar themes of nostalgia, loneliness, lost love, and death. He would sell 12 stories that year, and 22 the next. His stories were unusual, with a humane focus and distinctive imagery, earning him the nickname “The Poet of the Pulps.” But Bradbury worried about the literati dismissing him as a science fiction hack. In 1943, he would finally break into the slicks and in 1945 his story “The Big Black and White Game” was selected for the annual Best American Short Stories anthology. In the meantime he’d been approached by Arkham Press to assemble a short story collection, and Dark Carnival was released in 1947, a groundbreaking work of American Gothic horror. That same year, “Homecoming” was selected for the O. Henry Prize. Things were looking up, but it was his next book, The Martian Chronicles, that became a reference point for the rest of his writing career. A potent mashup of childhood nostalgia, Steinbeck’s The Grapes of Wrath, and Burroughs’ vision of Mars, it was a book with which Bradbury intended to transcend genre—and the critics agreed that he’d succeeded.

In his own search to find the reference point Crick had suggested, Perutz encountered the isomorphous replacement method, which introduced a heavy atom into a crystal that would not interfere with its native structure. The heavy atom could provide such a point, but it had never been attempted with such a large molecule. Further reading uncovered the fact that mercury associated with hemoglobin without interfering with its oxygen carrying capacity, and so in 1953, Perutz soaked some crystals of horse oxyhemoglobin (the oxygen-bound form) in mercury. The subtle differences in the patterns gave him the needed reference point, and six painstaking years later, with the aid of a punch card computer to handle the massive number of calculations, he had the structure. Hemoglobin had four chains, and the iron-binding heme groups sat in pockets on the surface of each. Interestingly, work on deoxyhemoglobin (not bound to oxygen) with his student, Hilary Muirhead, showed the heme groups were further apart, and in 1961 Perutz presented their findings at the Institut Pasteur, to a delighted Monod.

Bradbury followed up The Martian Chronicles with his last book of largely science fiction stories, The Illustrated Man (1951), full of metaphorical stories about civil rights, atomic war, and the misuse of technology. Meanwhile, Bradbury was welcomed into the literati, further inspiring him to publish more and more literary stories. In 1953, his first collection mixing SF and literary fiction, Golden Apples of the Sun (1953), was released. But it was his reputation within SF that finally earned him the opportunity to break into Hollywood with his first original story treatment for a movie, It Came From Outer Space, which turned the space invader trope on its ear.

It was this foray in film that exposed Bradbury to McCarthy’s Hollywood Communist witch hunts and in response, Bradbury produced perhaps his most enduring book, Fahrenheit 451 (1953). Bradbury also drew on his memories of the Nazi book burnings he’d seen in newsreels as a kid and from a bizarre encounter with the LAPD he’d had while walking. The novel was written in two sessions in the basement of the UCLA Library, where he pumped dimes into a rental typewriter, and Bradbury released it with Ballantine Books, a publisher who recognized science fiction’s literary potential. Bradbury was clearly on to something and Fahrenheit 451 was an instant success, garnering high praise from critics nationwide for its unflinching look at censorship and the dangers of mass-media-induced complacency.

Monod, too, recognized that Perutz was on to something important. For the preceding two years, Jean-Pierre Changeaux, a graduate student in Monod’s lab, had been working on the feedback control of an enzyme involved in isoleucine synthesis. Feedback inhibition (where the accumulation of the end product of a pathway inhibits its further production) appeared to be a standard tactic used by cells to regulate metabolism; Changeux had found, using different concentrations of substrate (what the enzyme acts on) and inhibitor (the end product isoleucine), that the change to the enzyme’s activity wasn’t linear, but sigmoid. This implied the enzyme was made of subunits, like hemoglobin, where the binding of the small molecules was cooperative, starting slowly, then proceeding quickly until slowing into a steady state. Changeux also used heat treatment to change the enzyme’s folding but found it maintained its substrate metabolizing activity while losing the sigmoid curve, meaning the substrate and inhibitor acted on different parts of the enzyme. Furthermore, the presence of inhibitor reduced the expression of the gene encoding the enzyme, demonstrating regulation at both the enzymatic and genetic levels. Listening to Perutz, Monod knew the conformational change of the enzyme must be responsible for hemoglobin’s behavior, and thus illustrative of a new principle he dubbed allosteric inhibition, the “second secret of life.”

Meanwhile, prior to the release of Fahrenheit 451, Bradbury had met the legendary director John Huston, whom he greatly admired, and upon giving him his books, Huston proclaimed they should write a script together. In 1953, Huston swept Bradbury off to Ireland to write a script for his Moby Dick adaptation. Huston was a difficult and often mean-spirited man and their time together was fraught, but Bradbury’s experience in Ireland deeply affected him and he would later write about it in shorter fiction, poems, and plays and in the novel Green Shadows, White Whale (1992). When he returned home in 1954, he found that he would never have to look for work again, being invited to write for Alfred Hitchcock Presents (turning down writing the screenplay for The Birds) and released a repackaging of Dark Carnival titled The October Country (1955). For years he had been writing stories about his childhood set in a fictional Green Town, Illinois, which led to the 1957 publication of the critically-praised Dandelion Wine, a beautiful and affecting book about a boy and his brother coming to terms with time and mortality during the Depression. He would go on to write two more books set in Green Town, Something Wicked This Way Comes (1962), and, much later, Farewell Summer (2006). By this point in his career, Bradbury had earned his immortality.

In 1965, Monod left yet another indelible mark on biology when he published his allosteric theory, which focused in large part on the sigmoidal curves for oxygen-dissociation for hemoglobin, the second notable discovery after DNA to tie structure to function. The theory held that allosteric proteins were made of identical subunits, joined symmetrically, which exist in a relaxed state when bound by its activator, or a tense state when bound by its inhibitor. Perutz’s further crystallography work found hemoglobin to be self-regulating, where oxygen bound to one heme group increased the affinity for further oxygen binding as conformational changes transmitted through the molecule, experimentally verifying Monod’s theory. Perutz would earn his own kind of immortality when he won the Nobel Prize for his work in 1962, the same year as Watson and Crick.

By the ‘60s, Bradbury was a household name. He served as “ideas consultant” for the 1964 World Fair, published books geared towards children, including R is for Rocket (1962), S is for Space (1966), and The Halloween Tree (1972), wrote a series of mysteries, consulted on the structure and storyline for Epcot’s Spaceship Earth ride, as well as producing more short story collections and novels, plus radio, television, and movie scripts. Adaptations of many of his works were made for film and television, including an HBO anthology series, The Ray Bradbury Theater (1985-1992) written by Bradbury himself. Bradbury would go on to win the Medal for Distinguished Contribution to American Letters and the National Medal of the Arts. He brought a deeper meaning to science fiction through metaphor and artistry throughout his life and career; after years of declining health, Bradbury died in 2012 at aged 91, donating his personal library to the Waukegan Public Library.

Unfortunately, Monod wouldn’t live to see the solving of the lac repressor. At Harvard in 1961, Benno Müller-Hill and Walter Gilbert created bacterial lines to producing high quantities of repressor to isolate it, and when crystallized in 1973, showed it, too, was a tetramer of identical subunits which bound to the operator region in the absence of lactose, but not in its presence. Their 1977 paper (published one year after Monod’s death) showed the N-terminus (the start of the protein sequence) bound the operator region of DNA, and the C-terminus (the end) bound lactose, and the two ends were joined with a hinge that transmitted the conformational change. Gilbert also worked with Allan Maxam to develop the first technique to sequence short pieces of DNA, thus identifying the seventeen palindromic bases the repressor bound to. Further work leading into the early 2000s would show there are many proteins of this type in bacteria, each with slight sequence differences recognizing different DNA regions and sugars, a trick used by every organism on earth, from bacteria to humans. Monod once remarked, “Life is controlled by a genetic program,” and in the end, he played no small part in uncovering its meaning.

Both science fiction and biology by the beginning of the 1960s had developed their fundamental toolkits, but what was coming for both was something decidedly new. Next time, we’ll look at the birth of the British New Wave through the work of J.G. Ballard, as well as the first scientific steps taken towards genetic engineering.

Book cover © Doubleday; Background image by NASA/JPL-Caltech/Univ. of Arizona.

Kelly Lagor is a scientist by day and a science fiction writer by night. Her work has appeared at Tor.com and other places, and you can find her tweeting about all kinds of nonsense @klagor

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