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 20-23Chapter Summaries & Analyses

Chapter 20 Summary: “A Human Tool”

Before gene editing, there was gene therapy. By 1990, scientists had begun working on introducing engineered DNA into the cells of humans. The engineered DNA was to behave like a drug, counteracting against a disease-causing faulty gene. There was no effort to change the patient’s DNA. Gene therapy was initially successful. In its first trial in 1990, scientists introduced functioning copies of a missing gene into the T cells of a girl suffering from a genetic mutation that impacted her immune system. The treatment worked, and she went on to live a healthy life. However, there were soon setbacks. Gene therapy triggered fatal hyper immune response in some patients. Clearly, removing cells from a patient, injecting the cells with DNA, and reintroducing the engineered cells to their system was not the answer. Researchers looked for a way to fix genes at the source, which paved the way for the field of gene editing.

There are a couple of prerequisites for gene editing: an enzyme that can cut the double strand break in DNA, and a guide to navigate that enzyme to the site where scientists want to make the cut. Enzymes that can cut DNA or RNA are known as nucleases. Researchers devised proteins like zinc-finger nucleases (ZFNs) and transcription activator-like effective nucleases (TALENs) to edit genes. However, CRISPR’s coming proved to be a game-changer. The biggest differentiator for the CRISPR system was that the guide was not a protein but an RNA (crRNA). Engineering different crRNA for different genes was far easier than developing different complex proteins. Yet CRISPRs left one major question unanswered: Could it work in the cells of complex organisms? The question set off a race in labs around the world to prove that Cas9-CRISPR could work in human beings.

Chapter 21 Summary: “The Race”

Doudna had never been embarrassed to appear ambitious, though she tempered her ambition with honesty and a collaborative spirit. For Isaacson, a healthy competitive spirit and a desire for glory are important attributes in a scientist.

The most heated competition of Doudna’s career so far rose with the race to show how CRISPR could edit human genes. Though many labs around the world joined the race, three main contenders emerged. One was Eric Lander’s mentee Feng Zhang (Broad Institute at MIT and Harvard), a man whose humble and cheery demeanor was balanced by natural ambition. Then there was Doudna’s longtime friend George Church (Harvard), a scientist driven more by natural curiosity than a competitive spirit. Finally, there was Doudna herself, “who was not only competitive but comfortable with her competitiveness” (163).

Chapter 22 Summary: “Feng Zhang”

China-born Feng Zhang was 10 when his mother, a computer science professor, decided to move her family to Unites States for a more application-oriented education for her robotics-obsessed son. Brilliant and hardworking, Zhang initially seemed set to become a computer science whizkid. However, at his Des Moines middle school, Zhang was gradually hooked on the study of enzymes, genes, and viruses. By the time he was at Harvard, majoring in physics and chemistry, a tragic incident further shaped the trajectory of his career. When his labmate Don Wiley, a master crystallographer, lost his life to possible suicide, Zhang became interested in researching cures for mental illnesses. That quest landed him to finish his postdoc work at a lab run by Doudna’s longtime friend George Church at Harvard Medical School.

Since his sophomore year, Zhang wanted to insert light-sensitive proteins into the neurons or brain cells of mice, so that light could stimulate the cells and thus map different circuits in the brain. His mechanism for delivering the proteins was viruses. However, inserting the gene for the light-sensitive protein into the exact location of the DNA of the brain cell had proven difficult, owing to the limited gene-editing technology of the time. At Church’s lab, Zhang found modest success with TALENs, since TALENs are tough to engineer and reengineer. However, Church encouraged Zhang to keep trying different methods for his research. They developed a close mentor-mentee relationship—till the day Church begin to believe Zhang had betrayed him.

Chapter 23 Summary: “George Church”

Growing up in Florida, George Church took his last name from his physician stepfather, whom he often accompanied on house visits. As a teen, he dug into his stepfather’s bag for hormones, which he used to make tadpoles grow. Prodigious in intellect and genial of spirit, Church worked his way into a PhD program at Duke University after two years of college. There, he became so engrossed in his lab advisor’s research on crystallizing RNA that he stopped attending classes and was thrown out of the program. Thankfully, he was accepted as a PhD candidate at Harvard Medical School, where he went on to work on sequencing DNA and developing genetic engineering tools.

When Doudna and Charpentier published their paper on the Cas9-CRISPR system in 2012, an excited Church wrote to Doudna, expressing interest in using the technology in human cells, and the two had a few conversations about using CRISPR in more advanced cells. The one person Church did not contact was Feng Zhang, since he says he was unaware of the fact that his former doctoral student was working on CRISPR in 2012.

Chapters 20-23 Analysis

Most of the bitter fight in the CRISPR field in the United States has revolved around who gets to patent the technology for genetic editing in humans. In Chapters 20-23, Isaacson first analyzes why CRISPR could be the perfect tool for gene editing, then profiles the contenders who wanted to be the first to deploy this tool. In the process, the text highlights many important motifs, such as the idea that the scientist is a flawed human, like any other.

What makes CRISPR a great tool for genetic editing is that it depends on crRNA. Different crRNA can be programmed to target DNA at different places far easily than the complex proteins of TALENs. Again, the humble and versatile RNA molecule emerges as the star of the story, a running theme throughout the text. Doudna’s prescient affinity for RNA singles her out as a visionary.

Chapter 21 debunks the notion of the unworldly scientist who couldn’t care less about glory. The truth is scientists are as human as anyone else and often work for acclaim and prestige. Moreover, ambition and competition can actually hasten crucial scientific discoveries. For instance, a fierce race between Japanese scientist Kitasato Shibasaburo and his Swiss rival Alexandre Yersin to discover the cause of pneumatic plague led them to isolate the responsible bacteria within days of each other. Therefore, the race for using CRISPR-Cas9 in humans wasn’t just par for the course; it may have hastened the advent of the technology.

Chapters 23 and 24 profile Feng Zhang and George Church in a way that establishes them as opposites. Scientist pairs, doppelgangers, rivals, and mirror-images are a recurring motif in the text, whether it be Darwin and Mendel, Watson and Crick, Doudna and Charpentier, or Zhang and Church. One key facet of Zhang’s personality is that though he was as “competitive as any star researcher, he was blessed with a cheery sweetness that made him uncomfortable displaying that trait.” (162) Thus, the text positions Zhang as a slightly “stealthy” player, a word that repeatedly crops up in relation to him. Whether the description is true of the real-world Zhang is debatable. However, to his credit, Isaacson also acknowledges Zhang as a gracious, warm scientist. The push-pull regarding Zhang reveals the text’s struggle to take an objective view of Doudna’s rival. It also opens up a larger debate about whether biographies can ever be fully objective, and more importantly, whether they should even try to attempt objectivity. Some literary theorists think writing a biography naturally aligns the author to their subject, which makes for a more involved, engaging profile. After all, a neutral distance can leave the biographer—and the reader—cold. Isaacson eventually acknowledges that the story he is narrating relies heavily on Doudna’s viewpoint, so pinpointing an absolute truth is difficult.

In contrast to Zhang, Church is described as “collegial” and uncompetitive, a venerable Santa-like figure with a large, spade-like beard. Unlike Zhang, who likes keeping his work private, Church writes to Doudna immediately after her 2012 paper about his interest in working on CRISPR. Zhang and Church’s differing modus operandi mean the two are bound to clash. Thus, Isaacson foreshadows their rift.