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 13-15Chapter Summaries & Analyses

Chapter 13 Summary: “Genentech”

In 2008, despite the excitement CRISPR was generating, 44-year-old Doudna was growing tired of basic science. Though CRISPR had the potential to be a gene-editing tool, Doudna wanted to do work that showed immediate results. She briefly considered going to medical or business school before a chance meeting with a former colleague who had joined the San Francisco biotech powerhouse Genentech.

Genentech was conceived in 1972 when Stanford medical professor Stanley Cohen and biochemist Herbert Boyer of the University of California, San Francisco, began working on recombinant technology, which combines DNA from different organisms. Cohen and Boyer combined DNA fragments of different organisms and cloned millions of them, giving rise to the field of biotechnology. They managed to patent recombinant DNA technology, even though Stanford’s Paul Berg, the discoverer of the technology, thought the patent unfair and “dubious.” (For his work on recombinant DNA, Berg received the Nobel Prize for Chemistry in 1980.)

One of Genentech’s earliest successes was making synthetic insulin, an achievements that changed the lives of diabetics—and farm animals—around the world. Prior to this, 1 pound of insulin required 8,000 pounds of pancreatic glands ripped from thousands of pigs and cows. By the time Genentech started wooing Doudna in 2008, the company was worth $100 billion. Excited about working in applied science, Doudna asked her team to prepare to follow her to San Francisco.

But as soon as she began working with Genentech in early 2009, Doudna realized she had made a mistake. Instinctively uncomfortable in her new role, she nearly had a nervous breakdown. With the help of a colleague at Berkeley, Doudna was back in her lab two months later. The experience made Doudna realize she was a research scientist to the core. Bringing her research to the practical domain would require forging a new path.

Chapter 14 Summary: “The Lab”

After her return to Berkeley, Doudna focused on hiring and mentoring the right young researchers for her lab. Rachel Haurwitz, a PhD student at Doudna’s lab who joined as a postdoc, jumped into the field of CRISPR. Wiedenheft enlisted Haurwitz to work out the structure of “problem child” enzyme Cas6, which was notoriously difficult to unveil. Once they figured out that the difficulty arose because the bacteria’s genome had been annotated incorrectly in databases, Wiedenheft and Haurwitz were able to create Cas6 in the lab.

But what was Cas6’s job, and how did the enzyme carry it out? Wiedenheft and Haurwitz conducted biochemistry experiments which revealed that Cas6 latches onto the long RNA made by CRISPRs and shears them into short RNA CRISPR segments that attack the DNA of viruses. With Jinek’s help, they also discovered how Cas6 latches onto CRISPRs and snips them. Cas6 has an “RNA hairpin,” which can attach to the right sequence of RNA so that it does not mess up other RNA sections.

Meanwhile, Sam Sternberg, a PhD student at Berkeley, also joined Doudna’s lab. Sternberg wanted to apply single-molecule fluorescence microscopy to study one of the Cas proteins. Doudna immediately agreed, liking Sternberg’s out-of-the-box approach. Doudna helped Sternberg to go to Columbia University and study the technique under its pioneer, Eric Greene. Ultimately, Doudna’s team and Eric Greene made a breakthrough discovery about how the CRISPR system’s RNA guided proteins found the correct target sequences of an attacking virus.

Chapter 15 Summary: “Caribou”

Despite her experience with Genentech, Doudna still nurtured the dream of developing practical applications for her lab’s discoveries. Haurwitz, who had just discovered the structure of Cas6 along with Wiedenheft, wanted to use Cas6 as a medical tool. How could the two women realize their dream? Doudna and Haurwitz wanted to go the way of Stanford University, where researchers were encouraged to partner with venture capitalists and entrepreneurs and patent their discoveries. These researchers often founded startups while retaining their faculty positions.

To prepare to run her own startup, Haurwitz enrolled in Berkeley’s school of business. In 2011, Doudna and Haurwitz founded their company, winning a spot in a Silicon Valley incubator. They decided to call their company Caribou, a portmanteau of Cas enzymes and ribonucleotides. Initially, Haurwitz and Doudna had to use their own money to kickstart Caribou Biosciences. A two-woman startup did not inspire confidence in the alpha-male dominated world of Silicon Valley’s venture capitalists. Additional funding came from Berkeley, government grants, and the Bill and Melinda Gates Foundation. The Gates Foundation grant was for Caribou to develop Cas6 as a tool for detecting viral infections. In 2020, Doudna would receive more funding from the foundation, this time to use CRISPR systems to detect coronaviruses.

Chapters 13-15 Analysis

Developing Chapter 12’s theme about the need for collaboration between science and industry, Doudna’s career detour in Chapter 13 shows that the world of science need not be divided into universities and corporations. “Bench-scientists” sometimes feel they are working in a bubble, where their work has no immediate application. This is especially true for someone like Doudna, who is driven to see results. Yet working for a large biotech corporation made Doudna uncomfortable to the point of illness. The detour into Genentech also shows Doudna is not afraid to make—and admit—mistakes, a quality that is essential in a scientist. As Doudna builds her lab in Chapter 14, this quality is again emphasized. Doudna is herself fearless, and she inspires the same risk-taking attitude in her mentees, such as when she tells Sternberg, “If you don’t try things, you’re never going to have a breakthrough” (115).

The text suggests that Doudna’s desire to work with applied science would best be fulfilled in a smaller set-up with university affiliation. Forging her own path takes on added significance in Doudna’s context because she is a woman scientist. Working in the male-dominated world of a large corporation is not satisfying; women scientists need to evolve their own entrepreneurship culture backed by their unique values. That is why, in Chapter 15, Doudna and Haurwitz launch their own startup. Significantly, Haurwitz is described as the rare Silicon Valley entrepreneur who possesses self-awareness and humility, qualities that enable her to attract and retain the best talent. Haurwitz even joins a professional development group for young CEOS, which meets once a month to discover problems and solutions. Isaacson pointedly quips, “It’s hard to imagine Steve Jobs or Mark Zuckerberg joining such a support group” (123). The reference to Jobs and Zuckerberg establishes Haurwitz as a new breed of CEO, a departure from the egotistical tribe of tech geeks.

The manner of Caribou’s funding underscores the “three-way partnership of government, business, and academia” (123) as a propeller of great American inventions, another major theme in the book. The uniquely American mix of academia, business, and government—encouraged in the 1940s and ’50s by Vannevar Bush, who recommended that the government should fund research institutions and corporate labs rather than build its own lab—is behind many a great scientific discovery.