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November-December 2021

Volume 109, Number 6
Page 376

DOI: 10.1511/2021.109.6.376

THE CODE BREAKER: Jennifer Doudna, Gene Editing, and the Future of the Human Race. Walter Isaacson. xix + 536 pp. Simon and Schuster, 2021. $35.

CRISPR PEOPLE: The Science and Ethics of Editing Humans. Henry T. Greely. xiii + 380 pp. MIT Press, 2021. $27.95.


Henry Kissinger, Benjamin Franklin, Steve Jobs, Albert Einstein, Leonardo da Vinci: Giants in their fields and times, these men also have the distinction of having received full biographical treatment from Walter Isaacson, America’s most prolific recorder of lives of creative genius. Jennifer Doudna is the first woman to join Isaacson’s centuries-spanning pantheon, and though she does not quite rate a banner with her own name on top, she is the anchoring presence of his latest book, The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race, a sprawling account of scientific sleuthing, discovery, and competition for stardom.

From The Code Breaker.

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In Isaacson’s previous work, it was the outsize personalities of his male protagonists that bestowed timeless standing on their work; Steve Jobs, who was famous for his ability to distort the reality of others, is the most iconic instance. But Isaacson presents Doudna more as a case of the work having made the woman, as the title The Code Breaker implies. Much of Isaacson’s storytelling is devoted to developing the breathtaking claim that Doudna’s “code breaking,” which centered on the chemistry of RNA, was the key to remaking the “future of the human race.” Finding the secret of gene editing with RNA-based CRISPR technology becomes for Isaacson a feat second only to the cracking of the genetic code by James Watson and Francis Crick in 1953, and he wants us to believe that this advance will be far more consequential in changing our understanding of what it means to be human.

CRISPRs (clustered regularly interspaced short palindromic repeats) were a biological puzzle when they were first noticed in the late 1980s and 1990s by a handful of scientists around the world who were studying the DNA of bacteria and other microorganisms. They found mysterious repeating sequences of DNA (the “repeats” in the CRISPR acronym) within the genomes of these organisms. Between these stuttering repetitions were bits of more familiar DNA sequences, which they called spacers. In most bacteria, the CRISPR sequences were flanked by a CRISPR-associated (Cas) gene that encoded a Cas enzyme. Scientists eventually discovered that the CRISPR-Cas system was an adaptive immune response that these bacteria were using to protect themselves from invading viruses. The spacers are transcribed by the host cell into short CRISPR RNAs that associate with Cas enzymes to guide them to new invading viruses harboring the specific spacer sequence. Those viruses are subsequently inactivated by the guide enzyme complex, which cuts up their targeted genetic material.

Public awareness of CRISPRs increased dramatically in 2012, when Doudna and Emmanuelle Charpentier (with whom Doudna eventually shared a Nobel prize) published a seminal article in Science explaining in detail the underlying mechanisms of a particular bacterial CRISPR-Cas system that involves the Cas9 enzyme. The article also showed that the Cas9 enzyme can be combined with molecules of synthetic guide RNA and delivered into a cell to find and cut, or “edit,” strands of any organism’s DNA at the specifically targeted sites.

Often likened to the spell-check function of a word processor, CRISPR gene editing quickly gained recognition as a faster, cheaper, and more efficient alternative to traditional genetic engineering. The versatility and precision of the RNA-guided molecular mechanism promised revolutionary improvements in biotechnology. According to Stanford lawyer and bioethicist Henry Greely, the author of CRISPR People: The Science and Ethics of Editing Humans, CRISPR “leapt far beyond the existing tools—perhaps not as far as a chain saw leapt from a stone axe, but close.”

Like many science writers, Isaacson and Greely are kibitzers, delighting in their ringside seats close to the centers of discovery and their capacity to open up the arcane world of the lab to eyes less privileged than their own. In vignettes that loop back and forth in time, Isaacson presents himself as a scientist among scientists, as much at home in their workplaces as the principals themselves. His book bursts with people and is illustrated with images of every scientist, major and minor, who played a role in transforming CRISPR from an idea into an instrument. To make Doudna stand out in this kaleidoscopic array, he sometimes shortchanges her competitors. Charpentier is a prime example. Isaacson presents her as shy, stylish, and very French, a far cry from the gutsy, gender-conscious, market-savvy, ethically aware, strategic persona he attributes to Doudna. If Charpentier has her own scientific vision and passionate commitments, Isaacson does not tell us about them.

Greely keeps a greater professional distance from his characters, but he too is at pains to establish his familiarity with the players in his story. Brief, gossipy boxed inserts about CRISPR scientists appear along the way in his narrative; in these, he explains how he came to know each character, and, more curiously, he describes his personal attitudes toward them. (He “did not immediately take to” David Baltimore, for instance, but has “come to quite like and respect him.”)

Among CRISPR’s many uses, Isaacson and Greely are most fascinated by its potential for curing genetic defects, for perfecting and even improving on nature. They view CRISPR as having put control of our heredity into our own hands for the first time, and they appear to accept, against compelling biological and social arguments to the contrary, that genes will determine humankind’s future. The authors thus converge on a central claim: CRISPR is a game changer for life on our planet, and it will be used to alter our species profoundly. The only question is whether there should be any limits on its use. Neither Greely nor Isaacson shows great appetite for caution, so long as players they view as responsible are in charge.

Irresponsibility, in both books, is easily personified in a specific miscreant, who happens not to be an American: He Jiankui, a Chinese researcher who carried out experimental, heritable, germline gene edits of human embryos with the goal of ensuring that children produced through this procedure would be protected from the AIDS virus and thus spared the stigma that attaches to AIDS in China. Implantation of those embryos resulted in the birth of twins in 2018 and a third baby in 2019.

Three connected conclusions emerge forcefully from these two books. First, He Jiankui was a rogue scientist who stepped far outside the existing norms of science; Greely dismisses him as “an outlier as well as an out-and-out liar.” Second, if science has given us the means to improve our genetic endowment, then the only ethical choice is to use that power. (What constitutes improvement is mostly left unexamined.) Third, the best people to craft the rules governing the uses of CRISPR are the scientists who took the lead in developing it.

Kin Cheung/AP/Shutterstock; from The Code Breaker.

How readily should readers fall in line with these confident assertions? All three require critical reappraisal. He’s behavior was almost universally condemned by the leaders of Western science, and China went along. Following a closed-door investigation and trial, Chinese authorities convicted He of violating regulations and ethical principles, and he was sentenced to a hefty fine and three years in prison. Yet all indications are that He was operating with high-level state approval until public opinion turned against him. He was deeply enmeshed in the competitive global game of high-stakes science that Isaacson vividly describes. Young, naive, and a cultural outsider, He had interacted with America’s biological elite and felt encouraged by them to take risks in his research. I met him briefly in 2017 at a meeting in Berkeley that was hosted by Doudna and featured other important scientists in the field. From that meeting, He appears to have taken the message that ends justify means, and that it is a scientist’s duty to dare to break with convention when the results could benefit humanity. Sadly for him, he overestimated his power to get away with playing the rule breaker.

The irony is that, while deploring He’s individual actions, many scientists in the CRISPR community took his transgression as a sign that the barriers to germline gene editing were down, and what had seemed unthinkable just three years earlier was now not merely possible but even a moral imperative. Somewhat incongruously, Isaacson deploys the biohacker Josiah Zayner, a man who by definition operates outside of science’s normal ethical codes, to make the argument that “our humanity” was “changed forever” when an embryo’s genome was intentionally edited. Isaacson compares Zayner with Steve Jobs reciting lines from Apple’s “Think Different” commercial about “misfits and rebels and troublemakers” who “push the human race forward.” But if He simply imbibed and acted upon this very American vision of progress through disruptive innovation, what exactly was his crime?

That question calls for serious reflection on what improvement and progress mean in terms of human genetics. Yet neither Isaacson nor Greely explains why editing sequences of genetic code should be seen as equivalent to moving humanity forward. Neither addresses the scientific and ethical limits of genetic determinism or the increasingly significant role of private money and power in American science. Perhaps this accounts for the relative complacency with which both regard the idea that scientists themselves should make the rules that guide the directions and applications of their research, even when that research involves tinkering with human heredity.

For Isaacson, the case is simple. All parents want the best for their children. Isaacson’s heroine, Doudna, made an “ethical journey” at meetings she organized, and parents desperately seeking cures for their children helped overcome her early, visceral sense that human germline gene editing was unnatural. She is well equipped to guide us, Isaacson suggests, because she now feels comfortable both as a scientist and as a humanist. He glancingly acknowledges that our collective choices might make us “less flavorful, like our tomatoes.” There is no hint that parental preferences with regard to greater height, eye color, or even intelligence may be biased by culturally entrenched attitudes toward race, class, or gender.

Greely knows that things are more complicated. As his book documents, law matters, but mostly as an arcane system that must be got around with experts like him as knowledgeable guides. To be sure, scientific discovery does not unfold in a vacuum. There are background rules in place, including the as-yet-untested ban on the implantation of genetically modified embryos in the United States, but these do not go far enough. Greely advocates national legislation on editing the human germline on largely pragmatic grounds. He prefers clear rules, and he painstakingly educates his readers on the vagaries of the Food and Drug Administration’s jurisdiction—its limits, its ambiguity, and its failure to assign accountability. This is a formally correct but soulless picture of the reasons for regulating the uses of CRISPR, doing scant justice to the social, cultural, and ethical arguments for holding back. I suspect that Greely’s account would only encourage the libertarians who think that Science, with Greely’s capital S, should be left to chart its own ways forward.

These breezy books are easy reads, but they barely skim the surfaces of a technoscientific revolution—they focus more on what we can do with new technology than on why we should or shouldn’t do it. They illustrate the dangers of going native in science writing. To probe CRISPR’s threats and promises for humanity, we need more than celebratory tales of brave new worlds. We need deeper explorations of two questions: “Whose knowledge counts?” and “Toward what ends should that knowledge guide us?”

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