We Haven't Really Cracked the Code of Life
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BOOKS and insert a section of it into the by a school counselor that “girls don’t We Haven’t bacteria’s own genome in order to do science” to scientific stardom. The Really Cracked recognize it in the future. Doudna reader will feel like a fly on the wall at and her colleagues’ innovation eureka moments, in lab races, dueling the Code of Life was to configure and use this viral presentations, and patent battles. “mugshot” system to target and The apparently enormous market of JAG BHALLA insert specific genetic sequences, readers who require novelistic details in their nonfiction—such as the kind of sandwich over which To say that scientists now history-making discussions about understand life’s “code” is a recombinant DNA happened stretch. So, from the very title of (pastrami)—will be thrilled. Walter Isaacson’s latest biography, Isaacson, the author of several The Code Breaker: Jennifer bestselling books, including Doudna, Gene Editing, and the biographies of Steve Jobs, Future of the Human Race, he’s off Leonardo da Vinci, and Albert to a rocky start. And that isn’t the Einstein, is the rare raconteur only conceptual gap papered over who can enliven complex by this beautifully built behemoth. science and the people and To suggest that Doudna is a “code history involved in its making. breaker” is to compare her to, say, His masterfully edited jump- the British code breakers of World cut montages of awe-stirring War II who cracked the notorious scenes, sneaky ego battles to steal German Enigma code. But when it scientific credit, and criminally comes to DNA, our code breaking gene-edited babies won’t isn’t all it’s cracked up to be: if the disappoint. Allies had had the same level of But the book epitomizes a kind expertise in actual cryptology that of pop science game of telephone scientists now have with DNA, that isn’t merely harmless fun. they might well have lost World Isaacson’s narrative falls prey to War II. a three-step whisper-chain of The Code Breaker contains 481 information that’s common in pages of Oscar-level cinematic scientific storytelling. The first prose, providing a whistle-stop step is what experts say and mean tour of how Jennifer Doudna, given their deep background a biochemist at the University knowledge of their fields; the of California, Berkeley, and a large The Code Breaker: Jennifer Doudna, second is what science writers and supporting cast discovered and Gene Editing, and the Future of journalists grasp and choose to developed the gene-editing technology the Human Race highlight; and the final step is what known as CRISPR—an acronym for by Walter Isaacson. New York, NY: nonexpert (and often overtrusting) Simon & Schuster, 2021, 560 pp. clustered regularly interspaced short readers take away. Through this palindromic repeats. These repeating process, the information that DNA features were found to be part creating a flexible DNA cut-and- makes it into prestigious books of the defense system that bacteria paste tool. like Isaacson’s (mis)shapes the have evolved over their billions Isaacson deftly dramatizes public imagination and strongly of years of warfare with viruses. science-in-action vignettes, with influences the thoughtscape in which Enzymes associated with CRISPR surprisingly few pages devoted to policymakers and citizens operate. sequences cut up attacking viral DNA Doudna’s journey from being told Although Isaacson admirably SUMMER 2021 89 books wrestles with technical and moral other wordplay, like the palindromic some techies suppose we’re on our complexities, I argue that his tone repeats—the PR in CRISPR—that way to solving the hardest patterning and balance generate a highbrow “CSI were central to the tool’s discovery. problems in every science. This sort effect”—ill-founded beliefs resulting In addition, 926,535 “regulatory of untethered-from-reality tech- from (over)dramatic license and the elements” (think of them as boosterism has led to much misuse of elevation of entertainment above usage rules) are listed in what are talent, time, and treasure—and many accuracy. misleadingly called “encyclopedias disappointments. When Isaacson writes that scientists of DNA elements.” Again, scientists Plainly stated, it’s easier to see have cracked the “code of life” and are clueless about their meaning. We the absurdly wishful hand-wave-y can do “precise” gene edits, those can crudely cut and paste with tools thinking. The mind-bogglingly statements are true only in a narrow like CRISPR, but we are far from labyrinthine etiologies of diseases such sense; more broadly, they mislead. fluent in even the basics. Rather than as Alzheimer’s or various cancers just When molecular biologists use words having the “means to rewrite the aren’t in the same conceptual category such as “editing,” “engineering,” code of life,” as Isaacson suggests, it as single-gene illnesses (sickle cell, “coding,” “programming,” and is truer to say we are like monkeys at Tay-Sachs, Huntington’s). Quoting, “mapping,” they generally know—or molecular typewriters. as Isaacson does, a venture capitalist at least should know—that these are Isaacson stylishly mixes glancing saying, “We have in our crosshairs limited metaphors. In ordinary usage prudence with gee-whiz gushing. any disease with a genetic component. (i.e., outside biology), those words He usefully reminds readers that the … We can go in and fix the error,” involve systems in which all the Human Genome Project’s “grand without immediately throwing cold parts and roles are well understood. medical breakthroughs that were water on the claim amounts to more But that’s not remotely the reality in predicted” haven’t materialized, molecular malarkey. It’s like reasoning the fields of genetics and molecular even for single-gene disorders. But that since bicycles and nuclear biology. Although it’s rarely advertised, he slips right back into hype-laden submarines are both technically computational biologist Lior Pachter blather like “the great promise of vehicles, once we’ve cracked bike gears argues, “the reality is that we have gene editing is that it will transform we’ll soon be voyaging undersea. no idea how the genome functions, medicine,” giving humans the tools Nuclear subs aren’t complicated bikes. or what the vast majority of genes or to “control evolution.” Contrary And no amount of being great at gears variants actually do.” Isaacson does to the impression created by will get you there. little to clarify this confusion or to the Human Genome Project’s Mischaracterizing such conceptual counter the field’s glamorous hype-fest. puffery (a prior case of pop science distinctions and complexities isn’t Saying we’re “learning the language malpractice), many illnesses aren’t— just a harmless “zest for spinning,” in which God created life,” to quote even in principle—addressable at a phrase Isaacson uses to describe from President Bill Clinton at a White the level of genes. Many conditions fact-stretching by the geneticist Eric House event celebrating the Human arise from complex combinations of Lander, founding director of the Broad Genome Project, hints at a handier behavioral, social, and contextual Institute and now President Biden’s analogy. This god language of the factors in which genes play roles but science advisor. This hyping quickly genome is written in a script that which it’s hard to imagine will ever spins out of control, with many scientists can transcribe into English be “editable.” Isaacson describes a negative effects, including channeling letters (A, C, T, and G). But researchers real CRISPR treatment for sickle money away from boring but effective know what only a small fraction of cell disease (priced at $1 million per approaches to disease and giving the resulting words mean. Most of the treatment), but that sort of clean investors, the public, and disease approximately 20,000 entries in the single-gene flaw is rare. sufferers false hope. human genome “dictionary” remain Such distinctions matter. The Isaacson’s metaphors do a lot completely blank. It’s as if we had an presumption that hard problems are of questionable work. He sees Enigma decryption device but only a on a continuous spectrum with easy biochemistry’s “molecules becoming limited understanding of a smattering cases has been dubbed the “first step the new microchips” and compares of German words. fallacy”: it’s just a matter of taking “digital coding to genetic coding.” What’s more, most gene words more steps along the same path to But obviously in computers, “mean”—that is, do—many things. crack the most complex cases. We engineers build and understand every It turns out nature loves puns; it see this fallacy often in techno- component; that is not nearly the case is polysemic deep in its molecular optimist circles. Now that artificial in molecular biology. Evolutionary essence. Nature also seems to love intelligence can classify cat pictures, scientist and physician Randolph 90 ISSUES IN SCIENCE AND TECHNOLOGY books Nesse has called this fallacy “tacit perennial problem of any powerful many in the thinkerati seem highly creationism.” It presumes a design- technology: how does society ensure susceptible. For instance, Elon like evolutionary process of creating it is used only for good and not for Musk has said that “synthetic RNA systems with fixed parts, like cogs nefarious purposes? (and DNA) … basically makes the or microchips, that have separable The standard answer is solution to many diseases a software functions. In reality, life at the regulatory oversight and ethical problem.” Ray Kurzweil predicted cellular level seethes with rapidly checks and balances beyond the we will “realistically model all forming flash-mobs of varying whims of the inventors. Doudna biology” by 2030. Mark Zuckerberg molecular “parts” that operate in is “appalled” by the failure of and Priscilla Chan’s foundation will jostling crushes of a vast “Brownian the scientific community to self- “cure all diseases“ by 2100.