The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race, written by historian and journalist Walter Isaacson, is a profile of 2020 Nobel Prize winner Jennifer Doudna and an overview of the frontiers of genetic editing. Published in 2021, The Code Breaker was one of the year’s most anticipated nonfiction titles in science, debuting at number one on The New York Times nonfiction best-seller list. The book was especially relevant given its exploration of the role of gene-editing technologies like CRISPR in fighting viral pandemics like COVID-19. A former editor of Time, Isaacson also wrote the best-selling biography Steve Jobs (2011).

This guide follows the 2021 edition from Simon and Schuster, UK.

Plot Summary

The Code Breaker is an account of the science of genetic editing, beginning with the discovery of the concepts of evolution and heredity. It primarily focuses on Jennifer Doudna, who received the 2020 Nobel Prize in Chemistry along with French microbiologist Emmanuelle Charpentier for their work on the gene-editing tool CRISPR. Though Doudna is the book’s focus, Isaacson also pays tribute to the numerous other scientists who made her work possible. CRISPR has tremendous potential as a tool that can cure disease, but the ethics of making gene-editing available in the free market should be carefully considered.

Growing up in Hawaii, Doudna became an avid student of nature. Reading The Double Helix by James Watson as a 12-year-old propelled her in the direction of chemistry and genetics. The Double Helix is Watson’s account of his Nobel Prize-winning discovery of the double-helix structure of DNA. Doudna liked that The Double Helix played out as a detective story and featured the brilliant chemist Rosalind Franklin, whose work Watson’s team appropriated. Franklin’s example proved to Doudna that women could be scientists.

With a doctorate in chemistry, Doudna and her husband Jamie Cate found home at the University of California, Berkeley. Soon, the couple had their only son, Andrew. Doudna’s special interest was figuring out the structure of the molecules of biology. Doudna believed a molecule’s structure had to be fully visualized before its function could be understood. No molecule caught her fancy more than RNA, the neglected sibling of superstar DNA.

In 2011, Doudna met French microbiologist Emmanuelle Charpentier at a conference. The two women decided to work on figuring out how CRISPR—a technology microbes use to fight viruses—works. Bacteria remember a portion of an attacking virus’s code and copy it into their own genetic sequence. If the virus returns, bacteria use these spacer sequences to recognize and destroy the virus. Scientists, including Charpentier, had discovered that the CRISPR-complex has three essential components: the crRNA (CRISPR RNA), which contains some of the virus’s genetic code; a molecule called tracrRNA, which prompts the creation of crRNA; and a class of enzymes called Cas, or CRISPR-associated enzymes.

Doudna and Charpentier determined the precise mechanism of the three-component system. The crRNA guides the complex to a similar DNA sequence; the tracrRNA, which creates the crRNA, latches onto the DNA as a handle; and then the scissors-like Cas enzyme chops up the DNA. This mechanism was a hack humans desperately needed to fight viral illnesses. However, its potential extends far beyond viruses: CRISPR could potentially be used to eliminate cancers in human cells, making it a truly momentous discovery.

Doudna and Charpentier’s findings were published in the journal Science in 2012 and won the duo instant fame. However, around the same time, George Church of the Harvard Medical School and Feng Zhang of the Broad Institute at MIT-Harvard were separately working on CRISPR systems too. Soon, the three groups were drawn into a bitter race, with Zhang and Doudna warring over patents to use CRISPR in human cells. Though Zhang was ultimately awarded the patent, Doudna’s team later won a parallel claim.

Apart from treating diseases like sickle cell anemia, CRISPR can also be used as a gene-editing tool in germline or reproductive cells, making changes that can be inherited. For instance, as George Church showed, the CCR5 gene can be neutralized in embryonic cells to eliminate HIV. However, the idea of gene editing in germline cells is extremely controversial. Can it be used to eliminate, say, the gene for short height from a family line? Would that be ethical? Doudna was initially troubled by the idea of CRISPR-enabled gene editing in humans because of its potential to be misused as a weapon for bioterror. She began collaborating with the government agency Defense Advanced Research Projects Agency (DARPA) to research CRISPR-neutralizing mechanisms. While the scientific community debated the ethics of gene editing, another scientist blindsided everyone.

In 2018, He Jiankui edited the CCR5 gene in twin embryos from an HIV-positive father and an HIV-free mother. The first genetically engineered babies were born in China in November 2018, sending shockwaves through the scientific community. The principal objection to Jiankui’s edits were that they were not medically necessary, since HIV transmission from parent to child can be stopped in other ways. Jiankui was later incarcerated for his work and banned from research in biotechnology.

Despite Jiankui’s work, there is no absolute international moratorium on gene editing in germline cells. However, debates on the ethics of gene editing continue. CRISPR is such a simple and adaptable technology that it can be engineered even for genetic enhancements. Already, biohackers like Josiah Zayner are working to make CRISPR kits available in the free market. One of these kits, available online, can be used to make a frog’s muscles grow. This has raised a host of questions about what would happen if the technology fell in the wrong hands, whether people should be able to edit their embryos to create perfect babies, whether removing the genes for disease and suffering would lessen human empathy, and whether the painter Van Gogh would have created his masterpieces if his genome had been edited for mental illness.

These are important and pertinent questions, to which Isaacson admittedly has no answers. Perhaps the most pertinent criticism of gene-editing comes from Feng Zhang, who believes the expensive technology will only aggravate social inequality if rich parents are able to buy their children “better” genes. Unlike Zhang, Doudna’s views on the future of gene-editing are more optimistic. Though she initially felt a “visceral horror” at the thought of creating a potential tool kit for future Frankensteins, she has grown to believe that CRISPR’s life-saving potential outweighs its dangers. For a person suffering from a debilitating condition like Huntington’s disease, in which the muscles slowly die, a gene-editing treatment would be a miracle.

Doudna’s view on the necessity of gene-editing technology were prescient. In 2020, when the coronavirus pandemic spread across the globe, labs like Doudna’s and Zhang’s immediately began working on CRISPR-based diagnostic tests. When such tests are widely available, they can be a game-changer in the early detection of viruses, as well as the production of CRISPR-based antiviral therapies and vaccines. Since COVID-19 is unlikely to be the last pandemic of our time, gene-editing that makes humans immune to viruses is the need of the hour.

Isaacson agrees with Doudna’s measured approach. He believes that advances in gene editing must continue, with checks and balances in place. For this, scientists will have to collaborate with humanists. Isaacson also suggests that everyone study the gene editing and learn about the genetic code, much like children today learn digital coding. Biotechnology is poised to be the next big scientific revolution of the 21st century, and learning its language will enable people to use the technology wisely.