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

Nonfiction | Biography | Adult | Published in 2021

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Chapters 44-47Chapter Summaries & Analyses

Chapter 44 Summary: “Quebec”

“Biotech nerds” are no longer outsiders but mainstream heroes, especially in the age of CRISPR and the coronavirus crisis. However, though they are akin to digital tech geniuses like Steve Jobs, biotechnologists feel pulled between the thrill of new discoveries and concern about their ethical fallout.

At the 2019 CRISPR Conference in Quebec, Canada, Zhang had just beaten Sternberg in publishing a paper on a CRISPR-guided system that inserts a tailored jumping gene into a desired DNA location. Doudna and her team were enraged once again at what they felt was Zhang’s stealthy modus operandi. However, to Isaacson, it is clear Zhang was simply faster; his paper was meticulous, by no means a rush job. In Quebec, too, Isaacson spent time at dinner with Zhang, who is sharply opposed to the idea of germline editing. Isaacson and Zhang’s group of diners included CRISPR pioneer Erik Sontheimer and April Pawluk, an editor at Cell. As talk turned to the ethical implications of CRISPR, Zhang made an important point: In a world where some people don’t even have access to eyeglasses, imagine the consequences of opening the door to genetic enhancements for others.

Chapter 45 Summary: “I Learn Edits”

Being around CRISPR pioneers made Isaacson want to try his hand at genetic editing. He arranged to spend a few days at Doudna’s lab, where postdoc Gavin Knott was to teach him the basics of using the CRISPR-Cas9 system first in a test tube, then in a human cell. The experiment Knott started Isaacson on involved a snippet of DNA that can make bacteria resistant to the antibiotic ampicillin. Knott concocted some Cas9 with a guide RNA that would delete the gene. Though Knott made all the experiment’s components from scratch, Isaacson was astonished to learn that the RNA and Cas9 can easily be bought online. The successful experiment left Isaacson feeling like a “true gene editor.”

To edit a human cell, Isaacson teamed up with Jennifer Hamilton, another postdoc at Doudna’s lab. Editing human DNA is a greater challenge: While the bacteria Isaacson worked on had 2.1 kilobases, the human kidney cell he was to work on had 6.4 million kilobases. Additionally, penetrating the nucleus of a human cell is no picnic. The human cell in Isaacson’s experiment was engineered to glow fluorescent blue. Using CRISPR-Cas9, the plan was to deactivate this gene by making a double-strand break at a targeted place. Additionally, a new template would be supplied, which the cell would then absorb, changing three base pairs of DNA to glow fluorescent green. The experiment was successful, but Isaacson knew most of the credit lay with Hamilton. Yet the ease with which it was accomplished made Isaacson wary about what such technology could do in the hands of a rogue scientist.

Chapter 46 Summary: “Watson Revisited”

James Watson, the high priest of genetics, was more or less in exile by 2019, banished from meetings even at Cold Spring Harbor Laboratory, his former home ground. His increasingly polarizing statements contributed to this fall in grace: As early as 2003, he told the BBC that genetic engineering could “cure” people with low intelligence and that being “stupid” was a disease. Though Watson considered himself politically progressive and claimed he wanted to use genetic editing to better people’s lives, his language reflected his biases. In 2007, he crossed a line when he connected intelligence with race.

Though Watson later apologized for his remarks, his controversial views on race surfaced again. In a PBS documentary in 2018, he restated that Black and white people performed differently on IQ tests. Should Watson’s achievements be undermined by his repugnant views? Or should his intelligence excuse his lack of empathy? Though Isaacson firmly believes professional greatness can never make up for a prejudiced outlook, he chooses to profile Watson since he is an important part of Doudna’s story.

Right before the CRISPR Conference at Cold Stone Harbor in 2019, Isaacson met Watson at his well-appointed home in the presence of Watson’s son Rufus. According to Rufus, he had let his father down. He characterized his schizophrenia as “being dim.” Yet his description of Watson was packed with wisdom: Watson’s controversial statements merely reflected his “rather narrow interpretation of genetic destiny” (385).

Chapter 47 Summary: “Doudna Pays a Visit”

Watson requested that Doudna visit him during the 2019 CRISPR Conference, and she did, accompanied by Isaacson. Watson showed the two around his sitting room, studded with modernist drawings and art by the likes of Paul Klee and Joan Miro, among others. Most represented a human face contorted by emotion. Classical music played in the background, and Rufus and his mother Elizabeth seemed quiet and guarded. Even the usually impetuous Watson was careful with his words. Yet he expressed great excitement about CRISPR. His own double helix discovery described the world, but CRISPR makes it easy to change the world.

On their walk back from Watson’s house, Doudna expressed mixed feelings about the visit. The Double Helix was a book that changed her life, but she finds Watson’s views abhorrent. Because her own father, Martin, had an upsetting tendency to judge people, Doudna considers people in all their complexity. Watson is one such complex mosaic for Doudna. The wonder The Double Helix inspired in her youth is wrapped up with her discomfort at Watson’s ignorant and outdated statements.

Chapters 44-47 Analysis

Chapters 44 and 45 focus on continuing advances in the field of CRISPR gene editing, showing that though ethical debates go on, so does the frontier of technology. Doudna’s views on the impossibility of suppressing CRISPR seem more prescient than ever, as do Josiah Zayner’s views on the ease of performing gene editing at home. The text suggests that whatever one’s views on the subject, the future heralds the widespread use of biotech.

Through revisiting James Watson in Chapters 46 and 47, Isaacson examines important and relevant themes about how to judge professionally successful people who are morally questionable. More often than not, such people are privileged; more often than not they are men. Traditionally, genius has excused transgressions and even crimes in such people. However, contemporary views are beginning to hold them accountable. James Watson is one such person.

In 2007, Watson told journalist Charlotte Hunt-Grubbe that though it was assumed all humans had equal intelligence, “all the testing” suggested “not really” in the context of Africa. The derogatory statements appeared in London’s Sunday Times, and Watson was forced to resign as chancellor of Cold Spring Harbor.

By 2018, the controversy around Watson had subsided. Scientists like Eric Lander were even beginning to toast his achievements publicly, leading to online backlash. Meanwhile, as he turned 90 the same year, PBS decided to feature him as part of a documentary series called American Masters. The documentary’s release in 2019 showed Watson views on race were as problematic as ever.

So, the question remains: Why does Isaacson give Watson a major role in The Code Breaker? The choice is fraught, and Isaacson doesn’t have an easy answer. Ultimately, he includes Watson because he is telling Doudna’s story, and Watson is a part of her story. He cannot be edited out. Doudna’s views on Watson inform Isaacson’s choice. Despite Watson’s troubling views, Doudna has always considered him a mentor of women. Doudna’s own temperament demands she see people in “grayscale” or as a “mosaic” rather than as good or evil. However, it can be argued that Doudna’s view is informed by her own privilege as an educated white woman scientist in contemporary times. Rosalind Franklin likely would have found it difficult to hold such a measured view of Watson.