Biochemist and UC Berkeley Professor Jennifer Doudna ’85 and her team discovered CRISPR-Cas9, a game-changing gene-editing technique with tremendous possibilities for curing diseases of all kinds, thanks to its precision. But with that finding, Doudna (who is also a Pomona trustee) discovered something else—that a great revelation sometimes brings with it a lot of wrestling. In A Crack in Creation, she tells a story that is about both success and struggle. PCM Book Editor Sneha Abraham talked to Doudna about the implications of what might be the most revolutionary scientific breakthrough of our time. This interview has been edited and condensed for space and clarity.

Jennifer Doudna ’85

PCM: You say in your book that, as a research scientist, you need adventurousness, curiosity, instinct, grit, practicality. Where do you get these traits from, and who’s your greatest influence?

Doudna: I think it comes from a combination of innate curiosity—I think we all have it, certainly as kids—and appropriate encouragement from family, friends and mentors along the way. That mix gave me an open-mindedness to ideas and a way of figuring out how to ask questions about the natural world.

PCM: Did your Pomona education prepare you for this in some way?

Doudna: I am grateful to Pomona every day, honestly, because it was a liberal arts education that exposed me to so many ideas that I would never have come into contact with, probably, without having attended Pomona. Many smart people, lots of really bright students, and not only those interested in chemistry, as I was, but also people thinking about history, French, physics, mathematics and geography. All sorts of topics. It’s a rich intellectual environment that opens one’s mind to the incredibly interesting diversity of the world in terms of cultures, ideas and perspectives.

PCM: Was there a class or professor that really impacted you while you were here?

Doudna: I think [Professor of Chemistry] Fred Grieman. I know he’s retiring soon, but Fred Grieman was a newish professor at the time when I attended Pomona. He was teaching physical chemistry, and he was spectacular. I think he’s a great combination of really deep understanding of the material so that you could teach it in a very clear and comprehensible way—and it’s not an easy topic, as you know—but also somebody who was very human, very funny, great sense of humor, really great at connecting with students. We used to play softball together in the summertime, and he always had students working in his lab over the summer and would have barbecues and things like that. He was very good at teaching us students that you could be a terrific scientist, very smart and intellectual, and still have a life outside of the lab.

PCM: In the book, you talk about that moment of discovery, that moment of pure joy in your kitchen. What was that like for you?

Doudna: Well, I’ve had a few, I would say, such moments in my career, and in this case, it was really one of those rare times in one’s life when the stars align. In our case, the ideas had come together, the data for experiments we were working on in the laboratory had given rise to a really sudden understanding of, not only how the CRISPR bacterial immune system works, but also how it could be used in a really exciting way. And that night, that moment I describe in the book, was really one of just unadulterated joy thinking about how amazing it is to explore science and make a discovery that you realize is going to be really impactful and change the world in certain ways.

PCM: That discovery presents so many amazing possibilities Was there an immediate thought that came to mind?

Doudna: For me, it was probably thinking about opportunities to cure genetic disease. When I was in graduate school in the 1980s, my lab was located at the Massachusetts General Hospital, where a professor named Jim Gusella was mapping the gene that causes Huntington’s disease. It is a terrible neurodegenerative disease that people get usually in their 20s, 30s, 40s, and then suffer from for many years with progressive loss of neurological function. So, being aware of that gene mapping experiment that was done in the ’80s, and then fast-forwarding a couple of decades and realizing that CRISPR technology, in principle, will allow the correction of that kind of mutation was a really profound thought.

PCM: You’re a research scientist, but with this discovery, you’ve become an ethicist as well, right? Were you expecting that as this was unfolding? How has that unfolding been for you?

Doudna: Not at all. I was absolutely not thinking, originally, about the kinds of ethical challenges that would come up. However, it became clear over the ensuing months that CRISPR was working better than anticipated, opening game-changing opportunities in how we might treat existing patients and how the technology might help future generations. What would be the ethical impact and what would go into making the right society and species-defining decisions needed to be explored and debated. I went from being a biochemist and structural biologist, working in my lab on this esoteric bacterial system, to realizing that I needed to get up to speed quickly on how other kinds of technologies that have been transformative had been managed and handled by the scientists that were involved in their genesis. Because the field of CRISPR was moving so quickly, the ethical discussions needed to catch up.

PCM: This is a big question. Is there an ethical dilemma that you’re most concerned about with genome editing?

Doudna: Well, there are a few that have gotten a lot of media attention. I think I would say that, at least in the near term, what I worry about the most is a rush to apply genome editing in ways that might inadvertently harm people. That might be because of over-excitement or the desire on the part of a scientist somewhere to do something first. I think that competitive want to move ahead with new ideas can be a very healthy drive in science but it can also lead to problems. In this case, I really hope that there is a concerted effort globally to restrain ourselves and do things in a measured and thoughtful fashion that doesn’t get ahead of the technology and the ethical debate.

PCM: It raises a lot of questions about us as a society, right? In the book you write about some of the implications socioeconomically and politically. How do you see this unfolding for the good? What are the dilemmas there?

Doudna: That’s another really big question. The good news is that there are now lots of discussions happening about the ethics and appropriate uses of gene editing technologies. I think that’s great progress but how we ultimately deploy CRISPR is going to come down to the pace at which helpful applications are actually developed and approved for use. For example, one of the most promising applications is called “gene drive.” It is the ability to drive a trait through a population very quickly using gene editing. Gene drive could be a real environmental impact concern due to its potential to wipe out a species of mosquitoes and perhaps cause unknown damage to associated species and ecosystems.

On the other hand, if deployed correctly, gene drive could have a hugely positive impact on human health by preventing the spread of mosquito-borne disease, perhaps by adding a trait that made mosquitoes incapable of transmitting a particular disease such as Zika virus. This is the type of cost-benefit calculation that has to be made in each case.

PCM: With CRISPR, when you’re looking ahead, or maybe it’s happening now, what kind of effects do you see on the biomedical industry or pharmaceutical companies, or the health care industry? Because this will change a lot of how we do medicine, right?

Doudna: I think it will in a few ways. One effect is using genome editing to discover genetic causes of disease. I think that’s still a very big data opportunity, to figure out, not only single genes that might cause disease, but also genetic interactions. Where there might be genes that interact with others to create a risk for certain people that bear that particular genetic makeup. I think that’s important, and it leads to opportunities to target those genes with drugs, and drug companies are increasingly using CRISPR technology to do exactly that. We are also trying to mine the human genome for new potential targets and then use genome editing to correct those mutations or create, if not a cure, at least some kind of a palliative approach to genetic disease. I think that will happen increasingly, especially as challenges like how to deliver these molecules into cells are addressed.

I also want to mention the incredible commercial opportunities. I’m seeing a lot of young entrepreneurs starting their own companies focused on making use of CRISPR technologies, investors excited to contribute money, and growing opportunities for companies to partner in different areas ranging from biomedicine to agriculture. It is very exciting and these opportunities are not just for scientists, but also for people that have a variety of backgrounds such as business. It’s really an interesting convergence of young people with a mix of expertise.

PCM: You write a bit about food politics, and the issue of GMOs, and that gap between the scientific community and the public. What do you think is driving the narrative that you say is false, that GMOs are a danger to our health? What’s behind that narrative that’s being pushed by other people?

Doudna: I think it’s a couple of things. Partly, it’s a lack of understanding about what we mean when we say “genetic modification,” and the fact that essentially all the food that we eat is genetically modified, because it’s edited by plant breeders that introduce genetic mutations. You just have to reference back to what tomatoes looked like before plant breeders got involved. They were very different from how they are today but why is that? Well, changes to the DNA, of course, but those changes were introduced, not by a precision genome editing technology like CRISPR. They were introduced by random mutation and then selection for desired traits. So, the unknown that can worry the public is what other genetic changes come along to the ride? We know they do but we just don’t happen to know what they are. I think when people understand that, they start to realize that the whole definition of GMOs is a bit contrived.

Also, I think the public can be suspicious about the intentions of corporations. That perception that corporations do not have our best health interests in mind, that they are out to make money, and that they do not care about potential risks, choosing instead to forge ahead with “Frankenfoods” or whatever you want to call it. We have seen this in the media, and it’s potentially at the expense of people’s health.

It really comes down to those two things then — not understanding what genetic modification really means and how our current food supply was created by plant breeders, and also being suspicious of the real motivations of corporations. We need to take a step back and really ask ourselves, “What makes sense here?” Then, we need to take a thoughtful path forward that allows technology to advance and help us solve important challenges in a way that is responsible. It’s not an easy balance, but I think we have to try to tackle that.

PCM: So who decides how this technology is used? You talk about that being a dilemma, as well, between scientists and the public. How is that dialogue going, currently, and how do you see that developing?

Doudna: Right now, the way that science progresses is largely decided by scientists, and then there are funders. So, if the scientists have an idea, something they want to do in the lab, they have to get money to do it. If they’re getting money from the public, namely from the taxpayers, that involves typically writing a grant, writing a proposal that says, “Here’s the science that I want to do, and here’s why,” and submitting it to a review committee of peers who review and comment on it. For example, they may say, “Well, good idea,” or, “Not a great idea,” and they then make a recommendation to the government about whether that type of science should be funded. That is how it currently works.

Now, if you’re a scientist who has other kinds of resources that are from private money—you have a wealthy donor or a foundation—you have to convince those folks rather than representatives of the government. Either way it usually comes down to an idea on the part of the scientist, and then convincing somebody or some entity to pay the bills. There’s a lot of science that involves things that could cause risk to humans. There are various kinds of regulatory controls that are placed on that work and various kinds of panels or review boards approve those kinds of projects. However, there’s not a broader oversight other than that, and a number of scientists have commented upon the fact that, for example, institutional review boards, or IRBs, have rules for how researchers can do things like work with human subjects or human tissues. The issue is that the rules are different at every institution.

Since the IRB rules at my institution, UC Berkeley, are different than other universities, I could have colleagues working elsewhere that would be under a different set of rules. That’s something that various groups are looking at—ways to try to streamline. As you can imagine, it’s very tough because you have a lot of different people with different opinions about these sorts of things. So, it’s just an ongoing challenge that we have.

PCM: This is half-joking, but I was chatting with a friend about CRISPR, and he asked, “At what point can we clone ourselves, get out of work, and still get paid?”

Doudna: Wow. That sounds very ambitious. It’ll take a lot of work to not have to work. That’s all I can say.

PCM: It’s not in the immediate future?

Doudna: No.

Photos By Antoine Doyen

It was 2007. He was pushing 70. He and his wife had separated, and he was about to retire. Pages in his life were turning. It was time, he decided, to flip ahead to the next chapter.

Now, 11 years later, Charlie Crummer ’59, a one-time physicist in Southern California, lives in an apartment on the Île Saint-Louis, a quiet, mostly residential plot of land in the River Seine as it flows through the heart of Paris. He’s an inch or two over six feet tall, his white hair mildly scattered, as Einstein taught us a physicist’s hair ought to be. On the street, he winds a scarf around his neck, which isn’t actually a municipal fashion ordinance in Paris but might as well be. Inside a quiet, simple neighborhood crêperie, he relaxes over lunch as he talks about how the seeds of his move from California to France had pretty much been sown long before he shipped out. About how, really, it all started with a car.

But not just any car.

“It was a 1966 Citroën DS,” he says, smiling at the recollection. “Do you know it? A French classic. I’d been driving an old Chrysler—a real tank. I brought it to the repair shop and the owner had this ’66 DS, a Pallas, which was the luxury model. He said ‘Take it for the weekend and try it out.’ Fifty miles later I was a raving convert. This was 1972. Riverside, California.”

For car guys back then, the front-wheel-drive Citroën DS was a dream vehicle, with self-leveling hydropneumatic suspension, power steering, disc brakes and other features that were, for the time, trophies of cutting-edge engineering and an oddly attractive space-age body design. A decade ago, a poll of 20 top automotive designers named the introductory version of the iconic vehicle—the 1955 model—“The Most Beautiful Car of All Time.”

“I kept that car for 13 glorious years,” Crummer continues, “until one day it ran out of water and the engine was damaged. We were going on vacation and drove it as far as Sacramento airport and it died. I left it in the airport parking lot for quite a while and then sold it to a Citroën aficionado. It was approaching 200,000 miles; all it needed was an engine overhaul. I dream that somewhere it’s still on the road. It was a work of engineering art.”

“Really,” he says, “it was because of the Citroën that I fell in love with France. I knew it in 1977, when we took a family trip to France—we were there just a week, less than a day in Paris. That was my first time in the country, but when we left… I can’t explain it, but I felt kind of homesick. It was like leaving my hometown.”

He especially connected with Paris—the soaring churches, the endless art, the streets and squares—but he didn’t go back for more than a quarter-century. When he did return at last, for a short stay in 2004, he found the city’s appeal was still there. He visited again the next year, and the next. It was after his separation in 2006 that he began to think seriously about moving there. Moving—you might say—to his spiritual hometown.

The following March 28, Crummer retired from his job as a physics lab manager at UC Santa Cruz. That same day, he was on a plane to Paris.

He brought along his two big lifelong passions: physics and jazz. (Ask him to name his major influences and he’ll start with Albert Einstein and Charlie Parker.) Both interests go back to his time at Pomona. A physics major (he later earned a Ph.D. in quantum gauge theory at UC Riverside), he was a versatile reed musician who played oboe in the orchestra as well as jazz on several members of the saxophone family. “I remember playing Dixieland on an exquisite gold-plated Selmer soprano sax owned by a professor in the music department,” he recalls. “That was ‘Doc’ Blanchard. To this day, I’m amazed he let me borrow such a valuable horn.”

It being the 21st century, among the first things Crummer did in his new Paris home was to establish a blog, so he could express an occasional thought about his new surroundings and a stray opinion about the world as he sees it. He headed his page:

Charlie

in

France

Some thoughts and some pictures

Impressions of Paris and other random thoughts

In his first blog post 11 summers ago, he celebrated the city’s parks and alleys and gardens. He responded emotionally to the sound of the great 19th-century organs in the churches of Saint-Sulpice and La Madeleine (“Tears of joy well in my eyes, taking me by surprise. My heart swells in my throat and explodes with the passion of the moment”). He reported briefly on visits to two jazz clubs. In one, a tiny bar (“about 4m by 8m, good beer, not so good sandwiches”), the audience barely outnumbered the performers: There were, in total, three listeners, including Crummer; the band was a tenor sax player and a pianist (“I listen to the sound of six hands clapping as they finish each tune”).

And then: “I took my clarinet down to the Seine the other evening. I found a place where I could sit alone. Carefully, I put the horn together and then paused. Who am I? An old guy sitting in rapture beside the ancient river ‘flowing under’ that has lived its life continuously since before the first man came there to receive its succor. I’m a little nervous even though there is no one else around. I can’t remember any tunes so I just play some changes. The river is kind. It flows on.”

Crummer brought his clarinet and his alto sax to Paris; he left two other horns—a tenor and a baritone sax—behind. “A bari is too big,” he explains. “You can only take so much on a plane.” In a life reboot, wherever you go to, you take some of you along, you leave some of you behind.

To keep up his musical chops, Crummer downloaded a copy of the famous Universal Method of Saxophone, the sax man’s bible (“I had it as a kid”) for exercises. He started playing in a saxophone quartet. “The leader of our group is a tenor man who’s an economist,” he says. “He travels a lot, so we can’t rehearse regularly. We have a guy who doubles on soprano and alto, and I’m on second alto. The other two are the leader on tenor and another guy on bari. We play mostly jazz and tango. We have a terrific jazz chart by Gerry Mulligan, better than anything else I’ve seen from him. We also have great charts from Astor Piazzolla, the ‘nuevo tango’ composer.”

Not that joining a group means the end of his solo playing. “I look forward to the good weather,” he adds, “when I can walk down by the old coal ramp by the Seine and play, alone, next to the swans and ducks. It’s so romantic.”

His occasional blog entries, usually brief, are written at home or, on occasion, sitting on a bench in a park with a laptop and free wi-fi. He mentions musical events ranging from a solo balalaika concert to a quartet playing gypsy jazz in a church. He marvels at Paris architecture. He offers quick opinions on capitalism versus socialism (the way economist Milton Friedman uses them, they’re cartoon-like loaded terms, he argues, and “Life isn’t a cartoon strip”), on oil drilling and oil spilling (“It’s time to just leave things alone down in the deep ocean”), on gun deaths and the NRA (he’s very opposed), and on his kids (he’s very proud).

Lately, Crummer has also been guest blogging for a small not-for-profit publisher in San Francisco, which has appointed him its “Paris Bureau Chief.” Since he finds managing the French language an ongoing battle, he schedules weekly one-on-one sessions with a French woman in which they converse for an hour in French and an hour in English. He’s a retiree apparently with no shortage of ways to keep occupied.

The physics part of his life came along to Paris mainly in the form of a paper that has been, typically for the scientific world, years in the making: “Aerodynamics at the Particle Level,” a continuation of work he began back in Santa Cruz. The paper—90-some pages long—explores the collision of fluids with solid surfaces from the particle perspective. It has been posted online for comments and suggestions from the scientific community; he’s revised it multiple times. “The way aeronautical engineers design a wing,” Crummer explains, “is to look at a bird and make a model and put it in a wind tunnel. We actually know a fair amount about just why things happen as they happen, although not enough. But engineers don’t care; they just want to make something that works. I want to know what’s behind the phenomenon.”

Considering all the elements of his Paris life, could he return to the States? That may depend on someone who entered his life soon after he arrived in Paris: Christine.

During his first month in the city, at the coffee hour after a regular service at the interdenominational American Church in Paris, he noticed a woman across the room. “She looked like a damsel in distress,” he recalls. “I thought ‘Uh-oh, that’s trouble’ but I went over and introduced myself. This is a church for Americans mostly, but she was French. She had an apartment to rent on the Île Saint-Louis, and she was there to post a notice on the church bulletin board.”

The woman was Christine, and as it turned out, she wasn’t trouble at all.

At the time, Crummer had a six-month rental arrangement across town, so he didn’t need the apartment Christine was looking to rent out, but when the six months ran out they moved together to her childhood home in a close suburb, where she was able to care for her aging mother. “If I hadn’t been religious when I came,” Crummer says, “I would have been converted just because of the magical things that have happened to me since I moved here.”

Eventually, they took over the apartment she had been looking to rent that day, the apartment on the Île Saint-Louis. The island is just a few hundred yards from the tourist hordes around Notre-Dame Cathedral yet light-years away on the serenity scale. “I’ve been all over the city by now,” Crummer says. “The Île Saint-Louis is the absolute best location I can imagine.

“Christine would love to live in San Francisco—she’s thought about that for a long time. I might go back there with her. After all, she has a dream; she helped me realize mine, so what could be fairer? We might do six months and six months. There’s a lot to be worked out.”

He pauses a few seconds to reflect, then continues: “I’m thinking of the old saying: ‘Go with the flow.’ It’s all an adventure. We’ll see what happens.”