Walter Isaacson's Latest Biography, "The Code Breaker" is an Ode to Female Ingenuity in Science
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When I was a child in the seventies, there were few bookstores in my Tennessee hometown, so I relied on weekly visits to three libraries, my cards crimped and yellowed like scraps of medieval parchment. I recall one dense, challenging read: Madame Curie, Ève Curie’s biography of her mother, the first woman to win the Nobel prize in chemistry. Marie Składowska’s Polish girlhood; her marriage-of-minds with Pierre Curie in Paris; sudden widowhood; two Nobel prizes; death caused by exposure to radium, an element she discovered—the arc of her life stirred my curiosity. She towered over unprecedented breakthroughs that continue to shape science a century later.
Walter Isaacson’s The Code Breaker (Simon & Schuster) showcases another Nobel prize winner, Jennifer Doudna, PhD, whose pioneering work echoes Curie’s: CRISPR technology, an RNA-based form of gene editing, will enrich us for decades to come. Isaacson, the doyen of American journalism and a Renaissance-style artist in his own right, pivots off acclaimed biographies of Albert Einstein, Leonardo da Vinci and Steve Jobs to portray the first woman in his gallery of big ideas. “There are three great revolutions of our lifetimes: physics, digital, and now the life sciences,” he says, explaining his shift to Doudna as subject. The Code Breaker is panoramic in scope and yet a page-turner, reminiscent of The Hot Zone and Hidden Valley Road.
Like Curie before her, Doudna has carved her own path. The daughter of a literature professor, she grew up in Hilo, Hawai’i, where she roamed the Big Island’s volcanic slopes and lush hollows, wondering why hilahila grass would curl when she touched it. In her sixth-grade year, her father gave her a copy of The Double Helix, James Watson’s chronicle of the race to discover the structure of DNA. Watson presents his and his colleague Francis Crick’s accomplishment at the expense of another researcher, Rosalind Franklin, who haunts the backstage of The Code Breaker. Although Doudna was told that girls don’t do science, Isaacson notes, “nevertheless, she persisted.”
As an undergraduate at Pomona College Doudna immersed herself in biochemistry and then opted for Harvard for her doctorate. These were heady times for DNA, the information molecule; an international consortium known as the Human Genome Project was ramping up, committed to mapping the human genetic code—all those spirals of As, Ts, Gs, and Cs— and initially helmed by Watson himself. (The HGP was predicted to take twenty years, but wrapped up in a decade.) Doudna, though, chose to study DNA’s sister molecule, RNA, which was thought to be merely a messenger from DNA to cells in the human body, urging them to produce the enzymes and proteins necessary for life. She married Jamie Cate, another geneticist, moved her lab to the University of California in Berkeley, and gave birth to a son—all while wrestling with scientific puzzles off the well-traveled highway of the HGP.
As Doudna realized: nobody puts RNA in the corner.
The Code Breaker unfolds as an enthralling detective story, crackling with ambition and feuds, laboratories and conferences, Nobel laureates and self-taught mavericks. The book probes our common humanity without ever dumbing down the science, a testament to Isaacson’s own genius on the page. He keeps the chapters short, with subheads; the book moves at a clip as Doudna is drawn into the methods of CRISPR, in which RNA cuts and slices faulty DNA much the way an editor would delicately tighten a manuscript with her pencil.
After a chance meeting with French CRISPR expert Emmanuelle Charpentier at a conference in Puerto Rico, Doudna vowed to bear down on the technology. The therapeutic —and entrepreneurial—possibilities seemed endless. But there was a complication: other scientists were in the hunt, notably Feng Zhang of the Broad Institute of MIT and Harvard. Founded in 2004 by Eric Lander, PhD, a charismatic visionary and a chief architect of the Human Genome Project, the Broad is a gleaming warren of laboratories in Cambridge, Massachusetts, sporting a blue-chip roster of researchers and clinicians. (Lander is currently on a leave of absence from the Broad, awaiting confirmation as President Biden’s Director of the Office of Science and Technology Policy, the first cabinet post for a scientist in U.S. history.) Zhang was Lander’s protégé. While Dounda’s lab pushed hard to show that CRISPR could work in a test tube, Zhang’s used CRISPR to edit actual human cells.
A bicoastal war erupted, with patents on the line, court cases on the docket, and massive egos ready to rumble—Doudna and another grandee, George Church, in one corner, with Lander and Zhang in another.
The choreography of these scientists was occasionally disrupted by a few bad boys and girls, a generation thumbing their noses at Marquess of Queensberry rules. Isaacson revels in the story of Josiah Zayner, known for cooking up experiments in his garage and then injecting CRISPR into his body. “Zayner, with his bleached-blond forelock and ten piercings in each ear, thus became the poster boy for a new kind of biohacker, the spirited band of renegades and merry hobbyists who want to democratize biology through citizen science and bring its power to the people,” Isaacson writes. “In the drama of CRISPR, Zayner plays the role of one of Shakespeare’s wise fools, such as Puck in A Midsummer Night’s Dream, who [. . . ]pokes fun at the pretensions of the high-minded, and pushes us forward by pointing out what fools these mortals be.”
Isaacson also deftly delves into perhaps the most provocative issue surrounding CRISPR: designer babies. In the future CRISPR will benefit couples with known genetic diseases scattered throughout their families: Huntington’s, cystic fibrosis, or Tay-Sachs, for example. This is familiar terrain to me. In 2004, shortly after our oldest son’s diagnosis of Spinal Muscular Atrophy, or SMA Type I, a devastating neuromuscular disorder, my wife and I, unnerved by the 1-in-4 chance another child would be similarly afflicted, opted for a procedure called Preimplantation Genetic Diagnosis, or PGD. After a cycle of IVF, clinicians biopsied a single cell from each of our fertilized embryos, flew those cells in an icebox to a Michigan lab for analysis, and by phone the next day verified which embryos were affected. Our healthy fifteen-year-old twins are the fruits of these labors.
Isaacson lays out the basics of PGD with care, but then goes a step further: unlike sixteen years ago, when my wife and I depended on yay-or-nay for each embryo (with a 98% accuracy rate), CRISPR could swap out the defective gene for a healthy one. Doudna recognized the upside in eliminating physical and emotional agony for families, and CRISPR will likely help to cure SMA and other single-gene diseases. But she was nervous about unlocking a Gattaca-like future, in which parents could shop à la carte for their children’s traits: wavy blond hair, steely blue eyes, sculpted washboard abs. And with price tags that only the affluent could afford, CRISPR could widen chasms of inequity. As Isaacson opines: “The danger of genetic technology might not be too much government control. Instead, it may be too much individual control...one based on free choice and marketed consumerism.”
Enter He Jiankui, the poor-boy-makes-good Chinese CRISPR expert who successfully edited out a gene associated with HIV, allowing an HIV-infected husband and non-infected wife to give birth to twin daughters in 2018, stunning the world. For the first time a species had deliberately altered its own code of life. The publicity was explosive, the blowback fierce, with Doudna at the center of the storm, compelled to craft ethical guidelines that somehow avoided a moratorium on the use of CRISPR in humans. Isaacson untangles the Gordian knot of technological achievements, moral concerns, and cultural differences.
CRISPR’s most immediate legacy may well be our current plague. As cities and nations went into lockdown a year ago, Doudna and her team went into overdrive, devising a diagnostic COVID-19 test. Her lab reached out to others, including Feng Zhang’s, sharing data in a spirit of collaboration. You can draw a straight line from CRISPR’s RNA underpinnings to the Pfizer and Moderna vaccines.
For Isaacson, our moment is a window into the near future, when CRISPR “home testing kits are as simple to use as a pregnancy test you’d pick up at a drugstore. Virology will come into our homes as personal computers did a generation ago, transforming medicine and health and our personal relationships to biotechnology. You’ll be able to determine whether your kid’s sore throat is caused by strep or a coronavirus.”
Doudna’s sweeping research and applications of CRISPR were exalted when she and Emmanuelle Charpentier won the 2020 Nobel prize in chemistry. The journey that commenced in Hawai’i culminated at science’s Everest. And as the pandemic rages on, a thrilling cadre of women have come to the fore: epidemiologists, physicians, and journalists who have amplified and interpreted data, lending clarity to confusion. Sarah Gilbert, Helen Branswell, Elaine Choo, Usmé Blackstock, Natalie Dean, Apoorva Mandivilli, Zeynep Tufekci, and Emma Hodcroft – know their names, follow them on Twitter, keep up as they lead us forward. As with Jennifer Doudna, they persist.
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