The Code Breaker, page 42
In 2020, the conference organizers tried to re-create the scene with a Slack channel and Zoom room called #virtual-bar. Its purpose, they said, was to “simulate the serendipitous introductions you would’ve experienced at the Blackford Bar.” So I decided to give it a try. About forty others showed up the first night. People introduced themselves in a stilted way, like at a real cocktail reception. Then a moderator broke us into groups of six and sent us to breakout Zoom rooms. After twenty minutes, each breakout session ended, and we were assigned randomly to a different group. Oddly, the format worked rather well when the conversations drilled down on specific scientific questions. There were interesting discussions of such topics as protein synthesis techniques and the hardware being built at Synthego to do automated cell editing. But there was none of the ordinary social chat that lubricates real life and nurtures emotional connections. There was no Yankees game in the background nor sunset to share while sitting on the deck. I left after two rounds.
Cold Spring Harbor Laboratory was founded in 1890 based on a belief in the magic of in-person meetings. The formula is to attract interesting people to an idyllic locale and provide them with opportunities to interact, including at a nice bar. The beauty of nature and the joy that comes from unstructured human engagement is a powerful combination. Even when they don’t interact—such as when an awed young Jennifer Doudna passes the aging icon Barbara McClintock on a path through the Cold Spring Harbor campus—people benefit from an atmosphere that is charged in a way that sparks creativity.
One of the transformations wrought by the coronavirus pandemic is that more meetings in the future will be done virtually. It’s a shame. If COVID doesn’t kill us, Zoom will. As Steve Jobs emphasized when he built a headquarters for Pixar and planned a new Apple campus, new ideas are born out of serendipitous encounters. In-person interactions are especially important in the initial brainstorming of new ideas and the forging of personal bonds. As Aristotle taught, we are a social animal, an instinct that cannot fully be satisfied online.
Nevertheless, there will be an upside to the fact that the coronavirus has expanded how we work together and share ideas. By hastening the Age of Zoom, the pandemic will broaden the horizons of scientific collaboration, allowing it to be even more global and crowdsourced. A walk along the cobblestone streets of San Juan was the catalyst for the collaboration between Doudna and Charpentier, but the technology of Skype and Dropbox allowed them and their two postdocs to work together for six months in three countries to decipher CRISPR-Cas9. Because people have now become comfortable meeting in boxes on a computer screen, teamwork will be more efficient. A balance, I hope, will be struck: the reward for our efficient virtual meetings will be the chance to hang out together in person in places like the campus of Cold Spring Harbor.
Charpentier, remotely
At the end of Doudna’s scientific presentation at the conference, a young researcher asked a personal question: “What inspired you to work on CRISPR-Cas9 the very first time?” Doudna paused for a moment, since it was not the type of question that scientific researchers usually ask after a technical presentation. “It started as a wonderful collaboration with Emmanuelle Charpentier,” she replied. “I am forever indebted to her for the work we did together.”
It was an interesting answer, because a few days earlier Doudna had talked to me about her sorrow that she and Charpentier had drifted apart, personally as well as scientifically. She lamented that she continued to detect a frostiness and asked me if, in my conversations with Charpentier, I had picked up more clues about why. “One of the things I am saddest about in the CRISPR tale is the fact that I really like Emmanuelle, but our relationship fell apart,” she said. Doudna had studied French in high school and college, even at one point considering switching her major from chemistry to French. “I always had this fantasy of myself as a French girl, and Emmanuelle in some ways reminded me of that. I just adore her on a certain level. I wish we could have continued to have a wonderful close professional and personal connection and could have enjoyed the science and all of the things that came afterwards as friends.”
When she told me this, I suggested that she invite Charpentier to speak at the Cold Spring Harbor virtual conference. Doudna immediately seized on the idea and asked her, through the conference’s co-organizer Maria Jasin, to give the tribute to Rosalind Franklin or speak on any other topic. I followed up with Charpentier to encourage her to accept.
She hesitated at first, then replied that she had another meeting to attend remotely during that period. Jasin and Doudna offered to be flexible about the time and date, but Charpentier declined. Sensing her reticence, I tried a different approach: I invited her to join me and Doudna by Zoom the day after the conference for a private chat. I told her that I wanted to include their reminiscences at the end of this book. She surprised me by embracing the idea. She even emailed Doudna to say that she was looking forward to it.
As a result, we met online the Sunday after the conference. I had prepared a list of questions to ask. But as soon as Doudna and Charpentier came online, they began talking to each other and catching up, at first in the slightly stilted manner of people who have not seen each other for a while, and then, after a few minutes, more animatedly. Doudna began referring to Charpentier by her nickname, Manue, and soon they were both laughing. I turned off my video camera so I could leave the screen to them while I just listened.
Doudna talked about how tall her teenage son, Andy, had grown, shared a picture that Martin Jinek had sent of his new baby, and joked about an awards event she and Charpentier did with the American Cancer Society in 2018 at which Joe Biden told them that he did not plan to run for president. Doudna congratulated Charpentier on the success of her CRISPR Therapeutics company in curing sickle-cell anemia in its Nashville trial. “We published our paper in 2012, and here we are in 2020 and someone has already been cured of a disease,” Doudna said. Charpentier nodded and laughed. “We can be very happy at how fast things happened,” she said.
The talk gradually turned more personal. Charpentier recalled the beginning of their collaboration, when they had lunch at the conference in Puerto Rico, walked the cobblestone streets together, and ended up in a bar for a drink. Many times when you meet another scientist, she said, you know that you could never work with them. But their meeting was the opposite. “I knew we would be good collaborators,” she told Doudna. Then they swapped memories about working around the clock by Skype and Dropbox in their six-month race to decode CRISPR-Cas9. Charpentier confessed that she worried whenever she sent Doudna some writing for the paper they produced jointly. “I thought you would have to correct my English,” she said. Doudna replied, “Your English is great, and I remember you had to correct some of my own mistakes. It was a lot of fun to write that paper together, because we have different ways of thinking about things.”
Finally, when their exchanges began to lag, I turned on my video camera to ask a question. Over the past few years, you’ve drifted apart, both scientifically and personally, I said. Do you miss the friendship you had?
Charpentier jumped in, eager to explain what had happened. “We were on the road a lot because of the prize ceremonies and other things,” she said. “People were overloading our schedule, and we did not have any time to enjoy the in between. So part of the problem was the simple fact that we both became terribly busy.” She spoke wistfully of the week they had spent together in Berkeley in June 2012 when they were finishing their paper. “There is this picture of us, with me with a funny haircut, in front of your institute,” she said, referring to the picture that is at the beginning of chapter 17 of this book. It was the last time they had been relaxed together, Charpentier said. “After that, it was crazy because of the impact our paper had. We had little time for ourselves.”
Charpentier’s words made Doudna smile, and she opened up even more. “I enjoyed our friendship as much as doing the science,” she said. “I love your delightful manner. I always had this fantasy, ever since I studied French in school, of living in Paris. And Manue, you embodied that for me.”
The conversation ended with talk about working together again someday. Charpentier said she had a fellowship to do research in the U.S. Doudna had previously made plans, which COVID scuttled, to spend the Spring 2021 semester on sabbatical at Columbia. They agreed that they should coordinate sabbaticals. “Maybe in the Spring of 2022 in New York,” Doudna suggested. “I would very much like that, to be there with you,” Charpentier replied. “We could collaborate again.”
Celebrating with Andy and Jamie in their kitchen just after the Nobel Prize announcement
CHAPTER 56 The Nobel Prize
“Rewriting the Code of Life”
Doudna was sound asleep when, at 2:53 a.m. on October 9, 2020, she was awakened by the persistent buzz of her cell phone, which she had put on vibrate mode. She was alone in a hotel room in Palo Alto, where she had gone to be part of a small meeting on the biology of aging, the first such in-person event she had attended in the seven months since the onset of the coronavirus crisis. The call was from a reporter for Nature. “I hate to bother you so early,” she said, “but I wanted your comment on the Nobel.”
“Who won?” Doudna asked, sounding slightly irritated.
“You mean you haven’t heard?!” the reporter said. “You and Emmanuelle Charpentier!”
Doudna looked at her phone and saw a bunch of missed calls that indeed seemed to have come from Stockholm. After pausing for a moment to absorb the news, she said, “Let me call you back.”1
The awarding of the 2020 Nobel Prize in Chemistry to Doudna and Charpentier was not a complete surprise, but the recognition came with historic swiftness. Their CRISPR discovery was merely eight years old. The day before, Sir Roger Penrose had shared the Nobel in physics for a discovery about black holes he had made more than fifty years earlier. There was also a sense that this chemistry award was historic. More than just recognizing an achievement, it seemed to herald the advent of a new era. “This year’s prize is about rewriting the code of life,” the secretary general of the Royal Swedish Academy proclaimed in making the announcement. “These genetic scissors have taken the life sciences into a new epoch.”
Also noteworthy was that the prize went only to two people, rather than the usual three. Given the ongoing patent dispute over who first discovered CRISPR as a gene-editing tool, the third slot could have gone to Feng Zhang, although that would have left out George Church, who published similar findings at the same time. In addition, there were many other worthy candidates, including Francisco Mojica, Rodolphe Barrangou, Phillipe Horvath, Eric Sontheimer, Luciano Marraffini, and Virginijus Šikšnys.
There was also the historic significance of the prize going to two women. One could sense a tight smile on the face of Rosalind Franklin’s ghost. Although she made the images that helped James Watson and Francis Crick discover the structure of DNA, she became just a minor character in the early histories, and she died before they got their 1962 Nobel Prize. Even if she had lived, it is unlikely she would have displaced Maurice Wilkins as that year’s third honoree. Until 2020, only five women, beginning with Marie Curie in 1911, had won a Nobel for chemistry, out of 184 honorees.
When Doudna called the Stockholm number that had been left on her voicemail, she got an answering machine. But after a few minutes, she was able to connect and officially receive the news. After taking a few more calls, including from Martin Jinek and the persistent reporter from Nature, she threw her clothes into her bag and jumped in her car for the hourlong drive back to Berkeley. On the way she telephoned Jamie, who said that a communications team from the university was already setting up on their patio. When she arrived home at 4:30 a.m., she texted her neighbors to apologize for the commotion and camera lights.
For a few minutes, she got a chance to celebrate the news over coffee with Jamie and Andy. Then she made a few remarks to the camera team on her patio before heading to Berkeley for a hastily assembled virtual global press conference. On the ride over, she spoke to her colleague Jillian Banfield, who in 2006 had called her out of the blue and asked to meet at the Free Speech Movement Café on campus to discuss some clustered repeated sequences that she kept finding in the DNA of bacteria. “I am so grateful to have you as a collaborator and friend,” she told Banfield. “It’s been so much fun.”
Many of the questions at the press conference focused on how the awards represented a breakthrough for women. “I’m proud of my gender!” Doudna said with a big laugh. “It’s great, especially for younger women. For many women there’s a feeling that, whatever they do, their work may not be as recognized as it might be if they were a man. I would like to see that change, and this is a step in the right direction.” Later, she reflected on her days as a schoolgirl. “I was told more than a few times that girls don’t do chemistry or girls don’t do science. Fortunately, I ignored that.”
As she spoke, Charpentier was holding her own press conference in Berlin, where it was midafternoon. I had reached her a few hours earlier, right after she got the official phone call from Stockholm, and she was unusually emotive. “I had been told that this might someday come,” she told me, “but when I received the call I became very moved, very emotional.” It took her back, she said, to her early childhood and deciding, while walking past the Pasteur Institute in her native Paris, that she someday would be a scientist. But by the time of her press conference, her emotions were well hidden behind her Mona Lisa smile. Carrying a glass of white wine, she came into the lobby of her institute, posed next to a bust of its namesake, Max Planck, and then answered questions in a way that managed to be both lighthearted and earnest. As happened in Berkeley, most of the focus was on what the award meant for women. “The fact that Jennifer and I were awarded this prize today can provide a very strong message for young girls,” she said. “It can show them that women can also be awarded prizes.”
That afternoon, their rival Eric Lander sent out a tweet from his perch at the Broad Institute: “Huge congratulations to Drs. Charpentier and Doudna on the @NobelPrize for their contributions to the amazing science of CRISPR! It’s exciting to see the endless frontiers of science continue to expand, with big impacts for patients.” In public, Doudna reacted graciously. “I’m deeply grateful for the acknowledgment from Eric Lander, and it’s an honor to receive his words,” she said. Privately, she wondered whether his use of the word “contributions” was a lawyerly way to subtly minimize their Nobel-certified discoveries. More notable to me were his words about “big impacts for patients” in the future. It led me to hope that Zhang and Church and perhaps David Liu will someday win the Nobel Prize for medicine as a companion to the one that Doudna and Charpentier won for chemistry.
Doudna mentioned at her press conference that she was “waving across the ocean” at Charpentier. But she badly wanted to actually talk to her. She texted Charpentier repeatedly throughout the day and left messages on her cell three times. “Please, please call me,” Doudna texted at one point. “I won’t take much of your time. I just want to say congratulations on the phone to you.” Charpentier finally responded, “I’m really, really exhausted, but I promise I’ll call you tomorrow.” So it wouldn’t be until the next morning that they finally connected for a relaxed and rambling chat.
After her press conference, Doudna went to her lab building for a champagne celebration followed by a Zoom party where she was toasted by a hundred or so friends. Mark Zuckerberg and Priscilla Chan, whose foundation was funding some of her work, made a virtual appearance, as did Jillian Banfield and various Berkeley deans and officials. The nicest toast came from Jack Szostak, the Harvard professor who had turned her on to the wonders of RNA back when she was a graduate student. Szostak, who had won a Nobel in medicine in 2009 (jointly with two women), raised a glass of champagne while sitting in the backyard of his stately brick Boston townhouse. “The only thing better than winning a Nobel Prize,” he said, “is having one of your students win one.”
She and Jamie cooked Spanish omelets for dinner, then Doudna joined her two sisters on a FaceTime call. They talked about how their late parents would have reacted. “I really wish they could have been around,” Doudna said. “Mom would have been so emotional, and Dad would have pretended not to be. Instead, he would have made sure he understood the science, then asked me what I planned to do next.”
Transformations
By honoring CRISPR, a virus-fighting system found in nature, in the midst of a virus pandemic, the Nobel committee reminded us how curiosity-driven basic research can end up having very practical applications. CRISPR and COVID are speeding our entry into a life-science era. Molecules are becoming the new microchips.
At the height of the coronavirus crisis, Doudna was asked to write a piece for The Economist on the social transformations being wrought. “Like many other aspects of life these days, science and its practice seem to be undergoing rapid and perhaps permanent changes,” she wrote. “This will be for the better.”2 The public, she predicted, will have more understanding of biology and the scientific method. Elected officials will better appreciate the value of funding basic science. And there will be enduring changes in how scientists collaborate, compete, and communicate.
Before the pandemic, communication and collaboration between academic researchers had become constrained. Universities created large legal teams dedicated to staking a claim to each new discovery, no matter how small, and guarding against any sharing of information that might jeopardize a patent application. “They’ve turned every interaction scientists have with each other into an intellectual property transaction,” says Berkeley biologist Michael Eisen. “Everything I get from or send to a colleague at another academic institution involves a complex legal agreement whose purpose is not to promote science but to protect the university’s ability to profit from hypothetical inventions that might arise from scientists doing what we’re supposed to do—share our work with each other.”3
