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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. ’s latest biography, Isaacson, the author of several The Code Breaker: Jennifer bestselling books, including Doudna, Gene Editing, and the biographies of , 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 , 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

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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

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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. These storm” involving billions of proteins regulate—resulting in the birth Silicon Valley titans seem to express per cell. of gene-edited babies (the work a combination of tacit creationism, More disturbing is the prominent of a rebel Chinese scientist who is the first step fallacy, and plain role Isaacson gives to a biohacker currently serving a prison sentence). old hubris. They don’t seem to jester, Josiah Zayner, who playfully In his enthusiasm for Zayner and his have a handle on the tremendous chides the bureaucratic slowness approving quote of Steven Pinker intricacies involved in biology’s of biomedical regulation. Isaacson saying bioethicists should “get out level of complexity and its radical is so captured by the genes-as- of the way,” Isaacson makes clear his conceptual differences from human- code metaphor and the idea that disdain for this kind of oversight. built tech. rebels “push humanity forward” In Isaacson’s telling, the And although CRISPR that, “despite the dangers,” he biohacker Zayner hopes to edit technology is still in its infancy, writes, society should “tap into the away the pain of bipolar anxiety Isaacson uses the tech-triumphalist biological wisdom and innovation that he fears he will pass on to his trumpet to tug hard at our of crowds.” But Zayner’s declaration kids. Isaacson sagely intones that heartstrings, declaring it immoral that genetic engineering “is no eventually we may isolate genes that not to use gene editing to reduce harder than computer engineering” predispose to psychiatric disorders. suffering. As a “moral principle,” he should be disqualifying. And Here’s the first step fallacy at work writes, “everyone deserves freedom again, quoting him without again. There are good reasons from genetic disease.” Not only that: correction is tantamount to pop why many psychiatric conditions “Aren’t we obligated to look after the science malpractice. Rather than are unlikely ever to be genetically welfare of our children and future a wiki-wisdom of crowds, we risk addressable. The broken-brain- humans in general?” In addition the malice of mobs. Consider due-to-bad-genes doctrine hasn’t to treatments for disease, Isaacson computer viruses, which impose fared well. The World Health weighs whether parents should be costs on all of us. (With one desktop Organization, for instance, classifies allowed to use gene editing to give computer, I spent more on antivirus depression as a biopsychosocial their kids better lives by enhancing software over the years than on the condition with nine main causal height, musculature, or intelligence. hardware.) factors, only two of which are He admirably expresses concerns Doudna is much more cautious biological, and the rest behavioral about fairness and distribution; than Isaacson, and perhaps this and social. It’s an unfounded but, of course, we already have characteristic doesn’t fit his assumption that “the biology” a technology that can enhance swaggering rebel mold. This of every disease can be found at precisely those traits (and many difference may partly explain the genetic or molecular level. As more), thereby vastly reducing why she gets relatively few pages neurogeneticist Kevin Mitchell current human suffering. It’s called compared to the stars of his other pointed out on Twitter, for many food. A hundred and fifty million genius biographies. Doudna is “psychiatric conditions, [their] kids worldwide are stunted by deeply troubled that CRISPR biology *emerges* at the level of malnutrition (as many as 30% of could become “a toolbox for future neural systems” rather than directly children in some poor nations). Frankensteins.” She can “scarcely from gene products. They suffer below-normal height begin to conceive of all the ways [it] In biology, words like and weight and lack schooling might be perverted.” She describes “engineering” and “programming” because we collectively choose to a nightmare in which “Hitler with perpetuate a deeply mistaken use resources for other purposes. I’ll the face of a pig” asks her to explain genes-are-like-code belief to which grant high-tech moral cheerleaders CRISPR, which points to the Silicon Valley entrepreneurs and more credence when their

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everything-is-getting-better gospel recommend Isaacson’s vast, vivacious addresses such basic, non-cutting- book. The Code Breaker is a rousing edge necessities. epic narrated for our era’s approved Isaacson endorses the idea emotional palate, full of “passionate that innovators need large curiosity” and “fearless rebels.” financial incentives to ensure a Isaacson says he relishes the “joy” continued supply of life-improving of understanding the life sciences, technologies; we could call this and it shows. But let’s work harder at the need-greed innovation theory. the joyful details of using our tools, He asserts that “the benefits of old and new, to edit and engineer away competition”—as facilitated by immediately avoidable—nongenetic— proprietary intellectual property— suffering. “are great,” despite the “toxic effects” money can have on academic Jag Bhalla is a writer and entrepreneur. research. But his portrait of Doudna provides ample countertestimony to this idea. An endearing aspect of Doudna is her unmercenary spirit. She felt “incredible disappointment and disgust” at the maneuvering of venture capitalists to monetize CRISPR, and Isaacson is very clear that she, like many scientists, isn’t motivated by money. Isaacson describes an epic battle between the University of California and the Broad Institute over CRISPR patents that hindered research progress and was surely a vast misuse of prime cognitive resources. At the beginning of the pandemic, Doudna and her rivals in the CRISPR patent dispute immediately pooled their intellectual property on COVID-19 work. The patent battle also highlights the fact that almost all important innovations in science and tech aren’t solo genius eureka moments. They’re community efforts with several teams circling the same ideas. Doudna’s path is full of chance meetings, and her achievement rests on a great deal of collaboration. Who should get credit and financial gain from the vast collective effort of science? Even the idea of the Nobel Prize, which Doudna was awarded with her collaborator Emmanuelle Charpentier in 2020, embodies an impossible-to-justify hero worship. Exactly because we need better- informed debates about all this, I’d

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