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A conversation with Walter Isaacson, author of “The Code Breaker”

Biographer Walter Isaacson has profiled a number of eminent scientists of the past, from Leonardo da Vinci to Albert Einstein. In his latest book, The Code Breaker, Isaacson turns his attention to the life and work of a pioneering contemporary scientist—biochemist Jennifer Doudna. I interviewed Isaacson for an editorial we published in this issue that reflects on the unusual occasion of the publication of a book of this prominence that includes so much detail about the culture and inner workings of research and scientific publishing. A review of the book by bioethicist George Annas also appears in this issue of Science.

Below are some highlights from our conversation. The interview has been edited for clarity and length.

Holden Thorp: Why did you feel you had to start the book with a primer on molecular biology?

Walter Isaacson: I wanted to put CRISPR and gene editing in the historical context of Mendel and Darwin laying the ground for what becomes known as a gene, then structural biology helping us figure out how DNA works, and then finally, Jennifer picking up the torch as a structural biologist and biochemist to study RNA, which happened to have a lot of ramifications. I also wanted to make the book a journey of discovery, where the reader and I could know the joy of understanding how life works.

Holden Thorp: You’ve written about Ben Franklin, Albert Einstein, and Leonardo da Vinci. All had died long before your books on them came out. Did you think differently about writing about someone who’s still alive?

Walter Isaacson: Yes. The good thing about writing about somebody who is alive is that you can report in real time. You can stand by her side in the lab. You can lurk in her Slack channels. You can see moment by moment how history is being made. And Jennifer was extraordinarily open, just allowing me to do anything, talk to anyone, and be in all of her meetings. She never asked for any control of the book, or the right to change anything.

Holden Thorp: How did you decide to focus on Doudna, and what does she have in common with the other people that you have written about?

Walter Isaacson: I believe there’ve been three great innovation revolutions of modern time. They are the discovery of the three basic particles of our existence: the atom, the bit—which is information coded in binary digits—and the gene. I wanted to do this third great wave of innovation, and I wanted a central character who was involved in all aspects of it. What first fascinated me was her work on the structure of RNA.

Holden Thorp: It was so huge when that structure came out. It was almost as big as CRISPR.

Walter Isaacson: The original thrust of my book was how molecules cause the mechanics of life to happen, and RNA seems so key to that. Doudna came to Aspen about 4 years ago, and also talked about CRISPR. And it seemed that easy gene editing tools would be the most important biological advance, but also the most important policy and ethical challenge we would face.

I wanted to show that science is a team sport, so there are many other major players in the book, including Feng Zhang, George Church, Emmanuelle Charpentier, and Jillian Banfield. But I also wanted to show the impact that a stubborn, insightful, dedicated person can have because I think science is a mix of individual initiative and collaborative effort. As I started shaping the book, using Doudna as the central character became more and more appealing. And fortunately, it gets to culminate with her and Emmanuelle winning the Nobel Prize, and with her deploying teams to use CRISPR in the fight against COVID.

Holden Thorp: We were pretty excited about the Nobel Prize, as you might imagine, since the 2012 Science paper was so important.

Walter Isaacson: It was a spectacular paper, and it was handled expeditiously.

Holden Thorp: There’s a lot of stuff about journals in the book. Did you know all these things about scientific publishing?

Walter Isaacson: No. It was one of the dozens of little things that was a joy to learn, which is the importance of the review process for journals, and how that is central to the advance of science.

Holden Thorp: What did you learn specifically about Science that you might want to share?

Walter Isaacson: I learned the rigor and honesty of the review process is so crucial to the progress of science. And in an era that’s become loose with facts and truths, and skeptical about science, it’s useful to have bulwarks that believe that evidence matters, and intellectual honesty is our true north compass point.

Holden Thorp: Well, that’s music to my ears, and I think that’ll resonate with a lot of people. So, thank you for saying that.

Holden Thorp: Jim Watson’s very important in the book, and I thought it was remarkable that you and Jennifer went to see him. What are you hoping people will leave thinking about Jim Watson, and how should science handle his legacy?

Walter Isaacson: What I hope to convey is that human nature is complex. And that, in particular, when it comes to human traits, there’s a complexity that starts with having to understand the useful traits somebody like Watson has while denouncing and abhorring his prejudices and stubborn views. Even more complex is realizing that the good and the bad in people may be intertwined. I don’t forgive any of Watson’s prejudices and unscientific biases, but I find it important to see the person as a whole. Someday somebody’s got to figure out how to write all of this up in a way that puts Watson in proper perspective.

[When I later asked Doudna about the visit with Watson, she elaborated: “Walter was hoping there could be a symmetry to the story told in the book, which began with me reading Watson’s The Double Helix and being inspired by the work and the people it described. It would have been great if that inspiration could have been renewed or extended in some way…but the visit only confirmed that there would be no neat closure to this part of the storyline. From our meeting, I did not sense that Watson regretted or had reflected on his egregious statements and behavior.”]

Holden Thorp: In the book, you write about the unfortunate way Eric Lander wrote up CRISPR in his Cell paper, and the Jim Watson tribute that got him into hot water. But do you think Biden made a good decision making Lander his presidential science adviser and the director of the Office of Science and Technology Policy?

Walter Isaacson: Biden made a spectacularly good decision with Eric Lander. His drive, which sometimes leads to clashes with people, is part and parcel of his greatness. And he was a driving force on the human genome project. The Broad Institute is a driving force of miraculous import in translating genetic research into medicine. And his ability to get people to collaborate, and be a magnet for talent, is unsurpassed in America. He could not be a better choice.