On the Origins of Modern Biology and the Fantastic: Part 15—Star Wars and Polymerase Chain Reaction

Science and science fiction are indelibly intertwined, each inspiring the other since their modern birth in the Victorian Era. Good science fiction, like a sound scientific theory, involves thorough worldbuilding avoids logical inconsistencies, and progressively deeper interrogations reveal further harmonies. This series explores the connection between the evolution of biology and science fiction into the modern era.

“Do. Or do not. There is no try.” —Yoda in Star Wars: The Empire Strikes Back

What is there to say about Star Wars? What other franchise inspires such love and hate, often simultaneously within the same person? Even if you’ve never seen the movies, you know the quotes. You know the spoilers. What made it such a phenomenon was being in the right place at the right time, and the fact that it has something for everyone: It’s good versus evil. Magic and spaceships. Flash Gordon and Akira Kurosawa. Jungian ur-mythology and campy dialogue. Most of the love-hate can be traced to a creator who at first was convinced of Star Wars‘ failure, and who then became uncomprehending of its success. Both because of, and in spite of, that creator, Star Wars changed everything.

Before the 1970s, SF movies didn’t make money, and thus didn’t evolve like SF books had. The repeal of the restrictive Hays production code in 1968 led to grittier, more varied subject matter and experimentation with different genres, from Texas Chainsaw Massacre (1974), to Taxi Driver (1976), to the The Godfather (1972). Hollywood was even beginning to toy with different release paradigms—Steven Spielberg’s third feature, Jaws (1975), was released nationwide with a multimillion dollar advertising push, resulting in the first summer blockbuster. But studios remained skeptical of science fiction. Prior to the success of Planet of the Apes (1968) and 2001: A Space Odyssey (1969), Hollywood SF was largely B-movie trash, though French New Wave films like La Jetée (1962) and Alphaville (1965) revealed the artistic possibilities inherent in the genre, inspiring SF landmarks like A Clockwork Orange (1971) and Solaris (1972). While these movies blended into the dreary and pessimistic ’70s landscape, SF remained largely a cinematic curiosity. It would be Star Wars that would finally bring SF into the mainstream.

By the 1970s, biology was poised for another breakthrough. The Central Dogma illustrated how genetic mutations could lead to disease, but the tools for studying genes were crude, and only a handful of such genes were characterized. Genentech’s recombinant DNA technique was a revolutionary first step, but the process was tedious. First, you had to make a library by cutting up your DNA of interest, sticking the pieces in bacterial vectors to clone and store them. After that came the fishing expedition to find your gene of interest. It took Kary Mullis—a witty, LSD-loving, womanizing surfer with an affinity for conspiracy theories and a doctorate in biochemistry—to bring cloning to biology’s mainstream.

***

George Walton Lucas Jr. was born May 14, 1944 in Modesto, California. His father was a successful small business owner who indulged the young Lucas’ mercurial passions. As a kid, Lucas enjoyed drawing and building things, dreaming of becoming an architect. He also voraciously read comics, loving Superman and MAD Magazine, and adored the televised Flash Gordon serial. As a teenager, he got into cameras and cars, dreaming of speed as a race car driver. He modded his car and hung around the Modesto car scene, until a near-fatal accident two days before graduation made him reassess this latest preoccupation. He enrolled in junior college, aimless, still working on cars on the side. His interest in people led him to take anthropology and sociology courses; he also read Brave New World and 1984, and explored the art house film scene in Berkeley. In 1963 he met legendary cinematographer Haskell Wexler while working a pit crew, and Wexler would spend years encouraging Lucas to apply to film school. In 1965, Lucas enrolled in USC’s School of Cinematic Arts and told his father he’d be a millionaire by the age of 30.

Kary Mullis was born on December 28, 1944 in Lenoir, North Carolina. As a kid, he had an affinity for scientific experimentation, mixing chemicals from his chemistry set and the pharmacy to see what might explode. He went on to spend his afternoons in his high school’s chemistry lab, and majored in biochemistry at Georgia Tech. While in school, he taught himself organic chemistry, making compounds for a chemical supply company in a makeshift lab in a chicken shed. Always driven, Mullis was plagued by a lack of clear goals. He moved to Berkeley in 1966 for his doctorate, and his first experience with LSD led him to write a paper on the nature of time that was published by Nature. While his thesis was on bacterial iron transport molecules, he took classes in everything, and after graduating in 1973 he followed his first wife to Kansas where she started medical school. He wrote and worked at a bakery, but wound up back in the lab, and after his divorce he moved back to Berkeley, working in restaurants and doing grunt work at UCSF. There he attended a talk describing Genentech’s work cloning somatostatin, sparking his interest in DNA synthesis. Sick of the slow pace of academia, Mullis found himself in the right place at the right time when he took a job at Cetus Corporation.

At USC, Lucas, too, found himself in exactly the right place at the right time. He hung out with other film class nerds while he explored his love of sound, vision, and editing. He was constantly tinkering with ideas for a “good” version of Flash Gordon in his drawings, while he expanded his cinematic palate through such landmarks as Metropolis (1927), the films of Jean-Luc Godard and the French New Wave, and Kurosawa. He was naturally drawn to animation, and in 1965 he made his first award-winning short film, “Look at Life,” about war, racial tensions, and the civil rights movement. He stayed at USC for his graduate degree, and while editing films for the government, he realized he wanted to direct. Using borrowed equipment and enlisting his students from the Navy Cadet filmmakers’ class as cast and crew, he made THX 1138 4EB, an Orwellian short with striking visuals. This earned Lucas more awards, a Time magazine write up, and the friendship of fellow student Spielberg. After graduation, he also met Francis Ford Coppola, who was directing his first movie. Coppola took Lucas under his wing, and the two soon moved to San Francisco to start a production company, American Zoetrope. They talked Warner Brothers into funding a feature length THX 1138 (1971), which failed at the box office. Lucas was still thinking about his Flash Gordon movie, and when he couldn’t secure the film rights, he started writing a treatment for his own space fantasy, while brainstorming another (non-SF) movie to make him enough money to move ahead with his vision. Channeling Fellini and his own experiences in Modesto car culture, he co-wrote and directed American Graffiti (1973). It was an instant hit, earning the greatest return on investment in movie history to date, and at age 29, Lucas had become a millionaire.

By 1979 Mullis seemed to have found his passion in working as a DNA chemist, making short sequences of DNA, known as oligonucleotides, for Cetus’ genetic fishing experiments. But in 1981 a synthesizing instrument took over Mullis’ job, and Mullis moved onto to a project to detect nucleotide changes in target DNA sequences. Mullis dreamt up a method using target DNA, radio-labeled nucleotides, an E. coli-derived DNA polymerase, and a sequence-specific oligonucleotide “primer” to identify the nucleotide that came after the short sequence to which the primer was bound. Whichever radioactive base the polymerase incorporated after the primer could be identified by gel electrophoresis. Unfortunately, this required more starting material than they had available. On a summer night in 1983, while driving up to his cabin, Mullis idly thought about designing a primer that bound a short distance downstream of the first, but on the opposite strand, to confirm the identity of the incorporated base by checking the identity of its complement. Then the idea struck him: If he let the reaction go on long enough, he could make billions of copies of just the region between the two primers. The idea consumed him… It just might work!

With the cash from American Graffiti, Lucas started work on the Star Wars screenplay. It had to feature a dogfight in space—basically the SF version of battle scenes from the World War II movies he’d watched growing up. He drew elements from Kurosawa, E.E. “Doc” Smith’s Lensmen stories, and Dune, the book which had struck SF like lightning in 1965. Watergate and Vietnam got Lucas thinking about revolution and fascism, and Joseph Campbell’s Hero With a Thousand Faces (1949) gave him a mythological backbone for his story. Lucas asked Ralph McQuarrie, who he’d met through Spielberg, for promotional art, which both defined the Star Wars aesthetic and helped secure funding from 20th Century Fox. He hired John Dykstra, protégé of the effects mastermind behind 2001, for his newly founded visual effects company, Industrial Light and Magic. He recruited composer John Williams, hot off his iconic score for Jaws. Production began in 1976 and script doctors Gloria Katz and Willard Huyck rewrote Lucas’ wooden dialogue on set, injecting much of the humor and memorable lines. When production wrapped, late and over budget, Lucas, now broke, was convinced that the movie would fail, but Star Wars’ publicity rep, Charles Lippencott, wasn’t going to let that happen. He cut deals with Ballantine and Marvel, and promoted the movie to SF fans at San Diego Comic Con and Worldcon. When it was released in a limited number of theaters on May 25th 1977, the film made more money in one day than the theaters normally made in a week. Limited access and repeat viewers created a publicity storm that spawned massive lines for weeks. The movie was an unprecedented and fast-paced visual feast, a satisfying struggle between good versus evil, pitting the little guy versus the big guy—and the little guy won spectacularly. Because of Fox’s lack of confidence, Lucas’ contract gave him 40 percent of theater rentals, and fifty percent of merchandising proceeds. By Labor Day, Star Wars brought in $133 million, surpassing Jaws to become the highest-grossing movie of all time and establishing the summer blockbuster as a viable business model for Hollywood.

Back at Cetus, Mullis became suspicious, asking everyone he could find if they’d ever heard of someone trying what he now called Polymerase Chain Reaction (PCR). No one at Cetus took it seriously, though the principles it was based on were sound. The only person who shared his excitement worked at the company who made their oligo synthesis machine, seeing how it might be good for business. Regardless, by the end of summer Mullis had a plan to amplify a 400 base pair fragment from Human Nerve Growth Factor, which Genentech had published the sequence of in Nature. He performed his first experiment in September—he put everything in a tube, boiled it for a few minutes, added the polymerase, drank a beer and went home. The lack of results the next morning showed him that he needed to cycle the reaction, heating, cooling, adding enzyme, and repeating, since the E coli-derived polymerase stopped working at the temperatures necessary to denature DNA strands. For three months, Mullis kept at it, switching to a smaller target, and on December 16th, 1983 he generated the first PCR product and earned a $10,000 bonus. But it would be his colleagues, Randall Saiki and Henry Erlich, who used the technique to amplify a gene from genomic DNA and publish the first PCR paper in 1985. Meanwhile Cetus, understanding what they had, quickly put together diagnostic kits to test for AIDS and other diseases, while Erlich and Saiki were invited all over to give talks. As a result, Mullis became bitter and began to fight with his colleagues, denouncing them at professional meetings. Cetus issued Mullis an ultimatum and he left the company in 1986.

Thanks to the contract with Fox, Lucas rode his good luck into complete creative control and a guaranteed three quarters of the profits for the next two Star Wars films. Recognizing his weakness when it came to writing dialogue, Lucas recruited Lawrence Kasdan to write the scripts based on his work on Indiana Jones, and poured more money into ILM to improve what he saw as underwhelming effects in the first movie. But audiences couldn’t get enough: The Empire Strikes Back (1980) made $500 million at the box office and Return of the Jedi (1983) made nearly $600 million. But as Star Wars fever gripped the world, Lucas was bitterly disappointed. The strain of overwork had led to the dissolution of his marriage and he was baffled by the reaction to the movies. To him, the movies’ effects seemed slipshod, and didn’t meet his expectations, so he vowed to never make another Star Wars film and settled into a comfortable role as producer. Lucasfilm went on to make three flops: Howard the Duck (1986), Labyrinth (1986), and Willow (1988). But ILM’s success in creating the effects for Jurassic Park served as a temptation to return at last… Lucas might finally be able to make the Star Wars movies he had always wanted with the prequels to the original series. The successful theatrical releases of the Special Editions proved not only that could he have the effects he wanted, but that the audience was still there, waiting. Love them or hate them, Episodes I-III were Lucas’ fulfillment of that dream…only they lacked the collaborative editorial feedback he gotten on the original trilogy. Despite poor reviews and fan disappointment, the prequels (released in 1999, 2002, and 2005) made Lucas a billionaire. In 2012, Lucas retired from the business of making Star Wars movies and other blockbuster films, announced Episode XII, installed Spielberg’s longtime production partner, Kathleen Kennedy, at the helm of Lucasfilm, and sold the company to Disney, leaving the future of the universe in the hands of his fans, with the backing of very deep pockets.

Mullis moved to San Diego while Cetus further developed PCR, switching to a DNA polymerase from Thermus aquaticus, a bacteria that lives on thermal vents, which didn’t denature when boiled, then sold the patent rights to Roche for $300 million. Mullis finally got his recognition when he won both the Japan Prize and a Nobel Prize in 1993, earning him financial stability. Mullis would go on to consult, found a number of bizarre companies, surf, philander, publish an autobiography, and eventually die from pneumonia on August 7th, 2019. PCR rapidly became a fundamental procedure in labs that did everything from basic research to medical diagnostics to forensics. It made cloning easier and gave researchers their first tool with which could directly manipulate DNA and begin to ask more and more powerful questions.

Meanwhile, the success of Star Wars led to an explosion of visual, effects-driven SF, leading to film and television becoming the media in which science fiction is mostly widely consumed today. After seeing Star Wars, Ridley Scott was inspired to make Alien (1979), then Blade Runner (1982). James Cameron got so angry after seeing Star Wars and not being able to figure out how the effects were done that he quit his job driving trucks and talked his way into a job in ILM’s spaceship model shop. Hollywood’s newfound confidence in science fiction meant that Star Trek fans finally got the movies they’d wanted for years, as well as leading to more SF TV shows, movies, and spinoffs in general. Star Wars brought SF firmly into mainstream culture, changed how movies were made, and made lifelong science fiction fans of an entirely new generation, who have since passed their fandom down to several more generations. Once again: love it or hate it, Star Wars surrounds us, permeates our lives, and binds our science fictional galaxy together.

 

Up next, we’ll be looking at a more rebellious side of science fiction with William Gibson and the rise of cyberpunk, and see the ways in which these improved scientific tools and methods led to the development of DNA sequencing and the Human Genome Project.

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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