The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

Image of The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race
Author(s): 
Release Date: 
March 9, 2021
Publisher/Imprint: 
Simon & Schuster
Pages: 
560
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“[I]n a world beset by scientific illiteracy and misinformation, Isaacson is the gene whisperer we so desperately need.”

Generations of American schoolchildren have been launched into scientific careers by tales of the celebrated rivalries of discovery and invention: Joseph Priestley and Antoine Lavoisier racing to characterize oxygen, Edison and Tesla warring over electrical currents, Jonas Salk and Albert Sabin simultaneously pursuing the polio vaccine. The most legendary of these, of course, is the quest to unravel the molecular structure of DNA in the early 1950s that pitted Caltech’s Linus Pauling against Francis Crick and James Watson at Cambridge University and Maurice Wilkins and Rosalind Franklin at King’s College London.

Watson’s bestselling account of his team’s efforts, The Double Helix, has been criticized for casual sexism, their Nobel-reaping triumph tarnished by allegations that they poached crystallography data from Franklin. So one cannot help but delight in the irony of sixth grader Jennifer Doudna—herself a future Nobel laureate in chemistry—setting her sights on a scientific career (that would ultimately eclipse Watson’s) after receiving his book as a gift from her father.

“I guess I must have heard about Marie Curie,” recalls Doudna, “But reading the book was the first time I really thought about it, and it was an eye-opener. Women could be scientists.”

Doudna is now one of the world’s leading biochemists and a pioneer in the field of gene editing who in 2012, along with French microbiologist Emmanuelle Marie Charpentier, first proposed the mechanism by which the CRISPR-Cas9 enzyme complex can be harnessed to reprogram the DNA of living cells. She is also the central figure in Walter Isaacson’s enthralling and panoramic history of the ongoing genetic revolution, The Code Breaker.

Isaacson has already carved out a niche for himself among the more serious of America’s popular biographers, a 21st century William Manchester with a dash of gravitas and a Plutarchian eye for drama. In choosing subjects, he gravitates toward mavericks and innovators ranging from Leonardo da Vinci and Benjamin Franklin to Albert Einstein and Steve Jobs. But Isaacson is also a grand doyen of American journalism who has headed TIME magazine, CNN and the Aspen Institute, and who treads easily in the corridors of power. This distinctive lens allows him to interview and shadow leading scientific figures, including Doudna and Watson, on an equal footing that fosters clear-eyed assessments. The result is an impressively balanced account of the ethical debates and tussles over credit that proves both nuanced and persuasive.

At the nuclear core of The Code Breaker stands the race between Doudna and her competitors—most notably Feng Zhang of the Broad Institute—to develop a versatile gene-editing tool based on RNA technology. But while this competition is a race, of sorts, it is not a public duel between two adversaries like Amundsen and Scott sprinting toward the Pole. Rather, an engaging cast of international scientists provide incremental contributions, and the degree to which they receive recognition reflects both merit and politics. In that sense, The Code Breaker offers a primer on the inner workings of contemporary global research.

Isaacson situates the Genetic Revolution as the successor to the Digital Revolution of the late 20th century, emphasizing the transformative implications of his subject. The narrative is told largely, although not exclusively, from Doudna’s perspective. As such, it is something of a non-fiction bildungsroman—an investigation of how a junior researcher fascinated by nucleic acids becomes a savvy player at the pinnacle of science. Along with Doudna, readers learn that the line between collaboration and competition is often as thin as a nuclear membrane, as when Charpentier, with whom Doudna shared the 2020 Nobel Prize in Chemistry, hints that she discovered an essential component of the CRISPR-Cas9 gene editing system on her own before her collaboration with Doudna.

Sometimes the rivalries prove fierce. Doudna and Zhang, after initially attempting to commercialize their discoveries jointly, found themselves in a fierce legal battle over intellectual property. At the heart of this dispute is the question of whether orchestrating CRISPR-Cas9 to work in human cells (Zhang’s contribution) was an essential feature of the discovery, or whether this advance was a relatively obvious and inevitable step after its efficacy had been demonstrated in a test tube (Doudna’s and Charpentier’s contribution). At stake is not only money, but also prestige and legacy.

Playing the recognition game too aggressively can lead to accusations of foul play. That was the fate of Eric Lander, Zhang’s mentor, who published a history of gene editing in Cell that many perceived as unfair to Doudna. Yet failing to pursue credit with sufficient vigor can also have consequences. A Lithuanian researcher, Virginijus Šikšnys, whose work paralleled that of Doudna and Zhang, lacked their influence and has received far less acclaim.

Isaacson also examines the case of Chinese biophysicist He Jiankui, who in 2018 defied the norms of the international scientific establishment by using CRISPR-Cas9 to alter the human germline—producing three genetically engineered babies. He Jiankui anticipated a heroic reception of Watsonian proportions, and the Chinese media was initially supportive. Yet the backlash from the scientific community proved ferocious, and He Jiankui ultimately found himself fired from his university and imprisoned for his research. One man’s iconoclasm, it seems, is another’s grave misconduct.

Ethical issues arise frequently in The Code Breaker, which, in addition to providing a navigable history of genetic technology, offers a compelling introduction to the complex moral and sociological questions that stem from these advances. Isaacson explores the potential for curing scourges like Huntington’s disease and sickle cell anemia, but also the slippery slope that might lead to creating offspring that are more intelligent or athletic. In doing so, he makes eloquent and succinct work of laying out the parameters of the debate between advocates of individual liberties and of collective welfare, introducing readers to the ideas of philosophers John Rawls, Robert Nozick, and Michael Sandel. As in his past volumes, Isaacson displays his gift for making complex material enjoyable to read.

Of particular concern to Isaacson and his scientist subjects are the implications of gene editing for human equality, the fear that those with plentiful resources will use these technologies to expand the gap between wealthy and indigent. (Of course, the opposite might prove true:  Carefully managed, such advances could be harnessed to level the playing field between rich and poor, adding a genetic boost to those who cannot afford SAT tutors and tennis lessons.)  Doudna’s own evolution of the subject of germline editing proves highly informative, as she fends off those who would open the floodgates like He Jiankui, but also those who would impose a lasting moratorium.

The Code Breaker, while unvarnished and occasionally critical, never drifts into the cynicism of Arrowsmith or The Education of Henry Adams. Rather, Isaacson invites readers on a riveting expedition through biochemistry, structural biology, and academic politics that transcends the traditional scientific detective story and captures the raw, magical enthusiasm of living pioneers like Doudna and her colleagues. Isaacson’s tale proves as inspiring as The Double Helix, only far more balanced, a compelling introduction to a complex field that does for the human genome what Carl Sagan once did for the cosmos In a world beset by scientific illiteracy and misinformation, Isaacson is the gene whisperer we so desperately need.