Leonardo da Vinci. Benjamin Franklin. Albert Einstein. Henry Kissinger. Steve Jobs. Now UC Berkeley’s own Jennifer Doudna joins the pantheon of innovators with a full-length biography written by acclaimed journalist Walter Isaacson.
With his latest book, Isaacson, former CEO of CNN, focuses on an accomplished scientist who is not yet a household name, even though she won the 2020 Nobel Prize in Chemistry for “the development of a method for genome editing,” known as CRISPR-Cas9 technology. Doudna shared the prize with collaborator Emmanuelle Charpentier.
In The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race, which comes out today, Isaacson follows the UC Berkeley Professor of Biochemistry, Biophysics and Structural Biology from her childhood in Hawaii, to her early years as a student at Pomona College, a researcher at Harvard, University of Colorado and Yale, then Berkeley and her ultimate success as the co-discoverer of CRISPR-Cas9, a technology that has been called a game-changer for genetic research and that may well lead to cures for deadly diseases, fix genetic mutations and reshape what it means to be human.
The Code Breaker is part biography and part the story of the development and potential implications of gene editing.
“I think (readers) will come away with a much better understanding of the technique,” Doudna said via email of Isaacson’s book. “Gene editing is going to shape our future in many ways, so it’s important that it’s understood by everyone, not just the scientists working in the field.”
“I write about innovation,” Isaacson said from New Orleans in a telephone interview. “I’d written about the physics revolution in the first half of the 20th century, then the digital revolution in the second half. I believed that the first half of the 21st century would be a biotech revolution. For the past eight or ten years, I’ve been reading up on everything from genetic editing to genetic engineering to immunotherapy to vaccines.”
A professor of history at Tulane and a former editor of TIME Magazine, Isaacson has been CEO of the Aspen Institute and is the author of seven books, including The Innovators and The Wise Men.
Isaacson met Doudna when she came to speak at the Aspen Institute “six or seven” years ago. He was struck by her description of an easy-to-use tool to edit genes, seeing CRISPR-Cas9 as being “the most transformative innovation of our time,” and the one that would have “the most interesting ramifications for the future.”
Isaacson writes about how as a teenager Doudna came home one day and found a copy of James Watson’s The Double Helix on her bed, a gift from her father. The story of Watson’s, Francis Crick’s and Rosalind Franklin’s search for the key to DNA, the building blocks of life, captivated her. Watson’s memoir spurred Doudna to contemplate a career in science, only to be told by her high school counselor that only men could be scientists.
In his new book, Isaacson emphasizes how Doudna’s perseverance proved that statement to be a lie. Throughout The Code Breaker, Isaacson reveals Doudna as relentlessly competitive, yet admirably generous. Her husband, UC Berkeley Professor of Chemistry, Biochemistry and Molecular Biology Jamie Cate, and their son Andrew appear occasionally in the narrative but their private moments are mostly left unrecorded.
Doudna’s interest in genomics research extends back at least to her success in designing self-replicating RNA as a graduate student at Harvard. Almost everyone has heard of DNA (deoxyribonucleic acid), but it is the less famous RNA (ribonucleic acid) that does the heavy lifting when acting as a “messenger molecule” carrying instructions from the DNA, facilitating the assembly of the proper sequence of amino acids to make a specified protein.
Having worked together at the University of Colorado and Yale researching the structure of RNA, Doudna and Jamie Cate married in 2000. Doudna and Cate considered themselves lucky to receive employment offers at Harvard and MIT, respectively, writes Isaacson. But when Doudna received a call from Cal, Cate urged her to call back. “Berkeley is nice,” he said. The couple moved to Berkeley in 2002.
“I connected with Berkeley right away,” said Doudna. “I had realized that there were opportunities I wanted to pursue scientifically, and a large, diverse public university like Berkeley opens up so many interesting avenues to explore as a scientist.” At Cal, Doudna continued her research focusing on the structure and functions of RNA.
“I connected with Berkeley right away…a large, diverse public university like Berkeley opens up so many interesting avenues to explore as a scientist.” — Jennifer Doudna
Doudna first heard about CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) from Berkeley microbiologist Jillian Banfield while enjoying tea at the Free Speech Movement Cafe on the UC Berkeley campus in 2006, Isaacson recounts. Banfield was intrigued by these odd, recently discovered repeating sequences in bacteria DNA and wanted to figure out their functions by consulting with a structural biologist. The two agreed to collaborate, and Doudna began to add to her lab researchers to help solve the puzzle.
The collaborators discovered that CRISPR allows bacteria to remember which viruses have tried to infect them before, and then pass their newly acquired immunity to their progeny. Finding this quirk in bacteria, Doudna and other scientists sought to learn how to edit genes in other organisms – plants, mice and humans – and the race was on.
Throughout The Code Breaker, Isaacson emphasizes the metaphor of science as a competitive sport. Doudna calls competition “the fire that stokes the engine,” and in the race to show how CRISPR could edit human genes, she faced two major competitors with different attitudes and resources.
In chapters with such titles as “The Race” and “Doudna’s Final Sprint,” Isaacson spotlights the top contenders. He assesses Harvard’s Feng Zhang as “competitive as any star researcher,” but “blessed with a cheery sweetness.” George Church, who for a time considered himself Zhang’s mentor, was also Doudna’s friend, “a Santa-bearded vegan” driven by a “playful and earnest curiosity.”
Each had allies and teammates to assist them – Charpentier with Doudna, along with researchers Martin Jinek and Krzysztov Chylinski; Eric Lander with Zhang. Church and Zhang even worked together for a time. Isaacson finds telling details about each individual. With short, punchy chapters, The Code Breaker maintains a sense of urgency throughout, as each team attempts to stay ahead without breaching their code of ethics. The shifting allegiances between Doudna and Zhang are especially fascinating.
Doudna is celebrated by Isaacson as an excellent team leader, able to spot talented people who can work together.
“Being a magnet for great talent and getting them to collaborate is one of her strengths,” said Isaacson. “She’s also good a getting people to look at the big picture instead of getting immersed into the details of their experiments.”
Doing the research is only half the battle when it comes to a game-changer like CRISPR-Cas9. There are publications to be submitted and patent applications to complete. Isaacson recounts the race to publish seminal articles and to prevail in the resulting patent battles, with millions – perhaps billions – of dollars on the line. (In fact, Doudna’s biotech company, Caribou, announced last week it had raised $115 million in Series-C funding).
Fears about ‘thought experiments,’ ‘designer babies’
One particularly fascinating chapter of The Code Breaker is devoted to “thought experiments” about how CRISPR-Cas9 might be used to treat Huntington’s disease, sickle cell anemia and deafness.
As much as CRISPR-Cas9 technology promises benefits, potential abuses could lead to “designer babies.” For example, Chinese entrepreneur and AIDS researcher He Jiankui claimed to be able to use CRISPER-Cas9 to make germline edits in viable human cells, resulting in the birth of two supposedly AIDS-resistant babies born in China in 2018.
Doudna was appalled that the invention was being considered for such use.
“I was concerned that the race to do this had been motivated not by medical need or by the desire to help people but by a desire for attention and to be first,” she said. Experiments leading to permanent changes to a human individual’s genome must be avoided, argues Doudna.
When Charpentier and Doudna were awarded the Nobel Prize in October 2020, it was the first time two women had received the prize, without a male co-winner.
With The Code Breaker already scheduled for publication a few short months later, Isaacson said that on that October morning, “I woke up at 4 a.m. my time so I could hear the live stream announcement of the Nobel, hoping, but not expecting, it would be for CRISPR and that Jennifer Doudna would win. To me, it was just a great thrill to hear that.”
Isaacson dryly added, “The Nobel Prize award certainly helped bring the book to a proper climax.” Doudna herself had reportedly slept through the announcement and the first few congratulatory phone calls.
The final portion of The Code Breaker details how CRISPR is being used to fight COVID-19. On March 13, 2020, Doudna and her colleagues at Berkeley’s Innovative Genomics Institute met to focus on building in a matter of days their own 25,000 square-foot coronavirus testing lab. Douda and longtime rival Feng Zhang declared that they would make their findings available to anyone fighting the virus.
Anyone who appreciates science writing both graceful and compelling will be impressed by The Code Breaker. Isaacson takes an extremely complicated subject and finds the drama and sense of wonder in it.
“To guide us, we will need not only scientists but humanists,” Isaacson writes. “And most important, we will need people who feel comfortable in both worlds, like Jennifer Doudna. This is why it is useful, I think, for all of us to try to understand this new room that we are about to enter, one that seems mysterious but is rich with hope.”