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 37-39Chapter Summaries & Analyses

Chapter 37 Summary: “He Jiankui”

He Jiankui grew up brilliant but poor in a rural part of China’s Hunan province. Though his family couldn’t afford to buy him textbooks, Jiankui surged ahead in school, ending up a physics major at the University of Science and Technology in Hefei, China, and a doctoral student at Rice University in Houston. Branching off to biotechnology, Jiankui joined Stanford bioengineer Stephen Quake at a company that commercialized gene-sequencing technology. In 2012, Jiankui launched a similar company in China and soon became a millionaire. By 2018, Jiankui began to consider the field of genetic editing, specifically editing human embryos for genetic diseases. He was, however, against the idea of using gene editing for some kinds of enhancement, such as IQ.

In 2017, Jiankui wrote to Doudna, who invited him to a small conference in Berkeley. George Church, one of the speakers, discussed a variant of the CCR5 gene that could make a person less receptive to the AIDS-causing HIV virus. Church’s work resonated with Jiankui, who had been editing the gene in monkey and nonviable human embryos.

Jiankui now wanted to enable AIDS-affected couples to have babies who were protected from HIV. Back in China, he recruited 20 couples in which the husband was HIV positive and the wife HIV negative. Sperm was taken from the father, washed to rid it of the HIV virus, and then injected into the mother’s egg. To ensure the children would never be infected from the condition, Jiankui injected the fertilized embryo with CRISPR-Cas9 to target the CCR5 gene. The embryos were grown in a petri dish, and their DNA was sequenced to see if the procedure had worked. In one case, the embryos flourished, were implanted into the mother, and led to the November 2018 birth of twin girls Nana and Lulu, the world’s first genetically engineered babies.

Though the news sent shock waves through the global scientific community, Jiankui hadn’t exactly made a secret of his plans. His experiments were funded by corporate interests in China, and they had been well-publicized and blogged about online. Moreover, Jiankui had been updating his former American colleagues about his plans, some of whom, like Quaker, would come to regret not intervening more actively in Jiankui’s plans. The roles of others were more dicey, such as Rice University’s Michael Deem, Jiankui’s former PhD advisor who was caught on tape at the meeting where the Chinese couple consented to Jianjui’s procedure.

Why was the twins’ birth considered such a gray area? For one, the germline editing was not medically necessary. Two, its overall implications in the babies were unknown. In fact, Jiankui’s papers showed that in Lulu, some of the CCR5 mutation had been preserved. In both girls, there were also unwanted off-target edits as well as some cells that were unedited by CRISPR-Cas9. The long-term consequences of this are unknown. Yet Jiankui claimed he was only following the path of Western scientists like Church, who were discussing the potential of editing the CCR5 gene.

Chapter 38 Summary: “The Hong Kong Summit”

On November 23, two days before Jiankui’s news broke, Doudna received an email with the strange and dramatic subject line, “Babies Born.” It included a draft of a paper on the births that Jiankui had submitted to Nature. The timing of the email was interesting, since the Second International Summit on Human Genome Editing was being held in Hong Kong in three days. Since the emergence of rumors about his experiments editing embryos, Jiankui’s status as a speaker had been up in the air.

Doudna flew to Hong Kong a day earlier than planned to discuss Jiankui with Baltimore. Doudna, Baltimore, and other scientists decided that it was important to let Jiankui speak at the summit to debate the impact of his work. The day of Jiankui’s session at the Hong Kong summit, the atmosphere was charged with suspense. Jiankui described his work in germline editing, insisting that the CCR5 mutation could help millions of families in China. Despite Jiankui’s admission, during the question hour, scientists quizzed him about the possible uses of the CCR5 gene. Only Baltimore, Harvard scientist David Liu, and a professor from Peking University asked Jiankui if his work was medically necessary. Jiankui insisted his work was ethical. Besides, he had discussed it with collaborators in America.

Disappointed with the lackluster questioning, Doudna was also plagued with guilt: Had scientists like her contributed to Jinakui’s breach of ethics? She, David Baltimore, Matthew Porteus, and five other scientists decided to draft more specific guidelines on when germline editing should be done. Once again, Doudna was torn between pursuing CRISPR-Cas9’s life-changing potential as a gene-editing tool and larger ethical implications. In the end, the scientists released a statement that was very restrained, stating that Jiankui’s work violated international medical guidelines but not calling for a ban on germline editing.

Chapter 39 Summary: “Acceptance”

Josiah Zayner was clearly delighted by Jiankui’s work. Zayner felt it was a breakthrough act that had changed humanity forever. He hoped that using a combination of IVF and gene-editing tools, everyone would be able to edit their babies to specification. CRISPR technology was already on the verge of being easily accessible, and human embryos could be bought from any fertility clinic for a few thousand dollars. Now, a genetic abnormality could be eliminated from humanity, saving people the misery of diseases like muscular dystrophy. So far so good. But Zayner had no qualms about using germline editing to enhance a child’s IQ or physical appearance. Pursuing IVF with his partner, Zayner felt he—like every parent—had the right to give his child the best future imaginable. Genetically editing an embryo was merely part of that drive.

Controversial as Zayner’s opinions were, he was not an outlier. Doudna was surprised to find that her son Andy considered genetically edited embryos the logical next step to human evolution. Perhaps germline editing would appear as normal to Andy’s generation and his predecessors as IVF did to Doudna’s. Further, political and public reactions to Jiankui’s work were in line with Andy’s views. Politicians were very interested in the implications of gene editing for healthcare, including curing diseases like Huntington’s, Tay Sach’s, and sickle-cell anemia.

Yet one scientist who maintained a contrarian position was Eric Lander of the Broad Institute. Enlisting Zhang and Charpentier to his side, Lander asked for a complete moratorium on germline editing. Lander argued that germline editing would exacerbate social inequality, foisting the notion of perfect human beings. Lander’s objections to germline editing were pertinent, but Doudna felt a moratorium was unrealistic. Doudna’s views prevailed, and in September 2020, an international commission determined that while germline editing was currently not safe, in the future it could provide couples with reproductive options. No moratorium was issued.

Meanwhile, Jiankui’s fortunes plummeted. In December 2019, he was put on trial by the People’s Court of Shenzhen, which determined that Jiankui had deliberately violated relevant national regulations and behaved unethically. He was convicted to three years in prison and banned for life from working in reproductive science.

Chapters 37-39 Analysis

Chapters 37-39 are extremely significant because they describe the breaching of the germline, or “the red line,” as Isaacson calls it. In other words, they describe the one event scientists had feared and debated for decades: genetic engineering in viable embryos for reasons that are not medically necessary. Jiankui’s edits were not strictly essential. Simpler processes like sperm-washing and pre-implantation diagnosis can minimize the chances of HIV in offspring of AIDS-affected parents. However, Jiankui argued that his edits were worthwhile because they are permanent, ensuring a child will not get HIV in their lifetime, and because they are medically necessary in the Chinese context, since HIV comes with a huge stigma in China. Jiankui’s defense may be questionable, but it does raise questions about culture’s role in determining what is medically necessary. It can also be inferred that Western notions of medical necessity are not universal, another aspect that must be considered while framing international guidelines for gene editing.

If there is a villain in The Code Breaker, Jiankui comes close. Isaacson describes him as unpredictable and grandiose, arriving at Doudna’s hotel to discuss his presentation a day before the Hong Kong summit. However, to Doudna’s surprise, Jiankui did not want to bring up the twin births at the summit at all. The night before Jiankui is slated to speak, it is still unclear if he will bring up the most “explosive” event in the recent history of gene editing. One reason for Jiankui’s odd behavior could be that he was not sure of the extent to which he was backed by the Chinese government. With scientists in China criticizing Jiankui’s work, the government distanced itself from the issue. Yet, notably, the government’s stand on the twin births remained unclear. Against this backdrop, perhaps it is better to view Jiankui as a fallen hero rather than an out-and-out negative figure.

Jiankui’s experiments lead to a fresh wave of objections against gene editing. In Chapter 39, Isaacson explores some of the new objections to germline editing, as well as the growing acceptance of the technology. Some ethicists believe that leaving gene editing to individual choice and the free market would be disastrous for society. Lander’s objections around inequality are also pertinent, but since germline editing has already begun in China, banning it outright would only encourage secret breakaway groups that would work without regulation. The fact the 2020 statement by the international commission echoed the consensus of the Napa convention is proof the idea of gene editing is not as reprehensible as it used to be. Andy and Zayner’s responses to Jiankui’s “designer babies” are also pertinent. For Zayner, the experiments are a watershed moment, while for Andy, they are an expected step in human evolution. Clearly, the ideas of what is natural and unnatural are evolving, with many younger people seeing their tech and digital selves as extensions of their natural being. For young people like Andy, gene editing is not heresy or an impregnable red line, it is just the next generation of technology.