Her Discovery Changed the World. How Does She Think We Should Use It? – The New York Times

Talk

“It’s a little scary, quite honestly,” says Dr. Jennifer Doudna, who helped develop CRISPR gene-editing technology.

It’s entirely possible, maybe even likely, that during some slow day at the lab early in her career, Jennifer Doudna, in a moment of private ambition, daydreamed about making a breakthrough that could change the world. But communicating with the world about the ethical ramifications of such a breakthrough? “Definitely not!” says Doudna, who along with Emmanuelle Charpentier won the Nobel Prize in Chemistry in 2020 for their research on CRISPR gene-editing technology. “I’m still on the learning curve with that.” Since 2012, when Doudna and her colleagues shared the findings of work they did on editing bacterial genes, the 58-year-old has become a leading voice in the conversation about how we might use CRISPR — uses that could, and probably will, include tweaking crops to become more drought resistant, curing genetically inheritable medical disorders and, most controversial, editing human embryos. “It’s a little scary, quite honestly,” Doudna says about the possibilities of our CRISPR future. “But it’s also quite exciting.”
I don’t mean to put it pretentiously, but your work involves touching the fabric of life itself. Has doing that work given you any wisdom that you can pass along to younger scientists? And I don’t mean something like “If you try your hardest, your career will work out.” I mean deeper wisdom about the relationship between humanity and science. Well, at some level, we’re all scientists, because being a scientist is about being curious about our natural world. That’s true whether we’re studying black holes or slime molds or working on CRISPR. It’s about the process of discovery. I still feel that way about the work that I do. It’s funny — I was recently having this conversation with my teenage son, who is starting to think about, Do I want to work in a company or start my own company or become an academic? I think he has always been a little skeptical of my work. He’s like, Gosh, why do you put up with the university bureaucracy? I said to him: I have a unique privilege in my job where someone is paying me to work on problems that they’re not dictating to me. I can get some money to do it, and I can persuade a student to work with me, and I can just do it! There’s a joy to that.
But I’m asking from an ontological or theological perspective. What thoughts does having your hands in there editing DNA spark about our place in the universe? It does seem quite profound that just in the last few decades human beings have figured out “What is the genetic material? What does it look like? How is it replicated?” and then, increasingly, “How do we synthesize it, change it and, now, how do we edit it?” It’s not something that we could do today, but you can see all the technical pieces have come together that would allow us to, for example, make the DNA that would encode an entire organism. With CRISPR, you could imagine doing things with life that have never happened in nature but now are possible because we can alter the DNA at will. That is a profound thing. I’ve asked myself, and I think this is kind of unanswerable: Is this a natural progression of human curiosity about who we are, why we’re here, what is life? All those profound questions that scientists have been trying to answer by trying to uncover the actual chemistry of life. Now we have a lot of that knowledge. We’re still, in my opinion, very limited in our knowledge of what our genome actually does, but we have tools that allow us to start to uncover the remaining answers to those questions more quickly. So where are we headed with that? It’s a hard question to answer. If we were on a steady trajectory, it would still be hard to answer, but we’re on this accelerating trajectory. I’m thinking about computing, machine learning, all the hard tech that will change and accelerate the pace of discovery.
A lot of the discussion about the possibilities of gene editing are still to do with things that are way off in the future. In my lifetime — I’m 40 years old — how is my world most likely to be touched by CRISPR? Certainly in the food that we eat: I think CRISPR will have an impact in the near term — I’m talking about the next few years. There already is a CRISPR tomato that was approved in Japan. We’re going to see a lot more of that, and we’ll also see CRISPR being used to mitigate some of the effects of climate change. Those are two very real, tangible kinds of outcomes. I think that we’ll probably see CRISPR being used for things like diagnostics. There are F.D.A./E.U.A.-approved diagnostics for Covid-19, for example, that are based on CRISPR. Then in the slightly longer term, I suspect we’re going to see increasingly that there will be CRISPR-based therapies or even preventive treatments. This is still very much in the realm of research, but it’s interesting that there is already an ongoing clinical trial by a company called Verve that is looking at using CRISPR to reduce the genetic predisposition to atherosclerosis, meaning cardiovascular disease. That highlights what will be, I think, possible in the future. We’ll have knowledge about our own genetics and a way to intervene.
What about the ethics of all those gene-editing possibilities? That’s something you’ve been talking about for years now, but what would it look like to actually resolve those ethical issues? What is the green light we’d be waiting for that would make us say, “This form of gene editing was not OK yesterday, but it is OK today?” Maybe let’s start with, “Where are the ethical boundaries right now for CRISPR technology?” Two come to mind. One is using CRISPR in an agricultural setting where the CRISPR molecules could be spread through a population. For example, a population of insects. This is something called a gene drive that is demonstrated to work very effectively with CRISPR — could be very useful at controlling populations of, say, mosquitoes that spread disease. But at the same time it could clearly have environmental impacts that might be of concern. That’s one aspect. The other is using CRISPR in the human germ line. Meaning making changes in embryos that, if implanted to create a pregnancy, then would create human beings who have edits to their DNA that are not just affecting them but can also be passed on to future generations. Those are two distinct applications, but it’s fairly clear why both of those could have profound impacts that could be dangerous. Understanding that, and then thinking about how to proceed as the technology continues to advance, has been incredibly important. Let’s take the human-embryo example. Is there a particular event or decision or developments that would suddenly make us say, “Oh, we didn’t think it was OK yesterday, but now it seems fine?” No. But it’s a complex issue. There would be technical considerations. In other words, even before we ask, “Should we do this?” we have to ask, “Can it be done accurately and safely in a way that creates a change that is desired by the scientist who’s doing the work?” Right now that’s still not true in human embryos, I would say.
But it will be. The science will get there. So what questions do we need to be asking? That’s where that second bucket comes into play: If we can do it, should we be doing it? If we are going to do it, in what circumstances, and who decides? Because, as you said, the technology is going to get there. So what decisions would have to be made to use this in human embryos? You would need an appropriate reason to do it — and I don’t think the reason, at least not first up, should be something that doesn’t have a clear medical benefit. You would want to have a circumstance where you don’t really have other options. Then there has to be a process. If you were going to actually do this in some clinical study, how do you even set up something like that, for a thing this profound? If you asked 10 different people those questions, you’d probably get 10 different answers.
What would be an example of a borderline ethical medical use? An interesting example to contemplate is suppose that genome editing could be used to remove a gene that was implicated in developing cardiovascular disease. You could argue that as people age, that has a health benefit. You could also worry about the risks. The risk of getting cardiovascular disease is not 100 percent. Do we take the risk of genome editing versus the maybe low risk of cardiovascular disease? That would be the kind of decision that will have to get made in the future.
It’s also easy to imagine two different countries, let alone two different people, having competing ideas about what would constitute ethical gene editing. In an optimal world, would there be some sort of global body or institution to help govern and adjudicate these decisions? In an optimal world? This is clearly a fantasy.
OK, how about a suboptimal one? The short answer is: I don’t know. I could imagine that given the complexities of using genome editing in different settings, it’s possible that you might decide to use it differently in different parts of the world. Let’s say an area where a mosquito-borne disease is endemic, and it’s dangerous and high risk for the population. You might say the risk of using genome editing and the gene drive to control the mosquito population is worth it. Whereas doing it somewhere else where you don’t face the same public-health issue, you might say the risk isn’t worth it. So I don’t know. The other thing is, as you indicated with the way you asked the question, having any global regulation and enforcing it — hard to imagine how that would be achieved. It’s probably more realistic to have, as we currently do, scientific entities that are global that study these complex issues and make formal recommendations, work with government agencies in different countries to evaluate risks and benefits of technologies.
In Walter Isaacson’s book about you and your work, you mention this ominous dream you once had about Hitler. Then in your own book, you wrote about another portentous dream you had about an impending tsunami. Do you still have dreams like that? My dreams today are pretty pedantic, kind of boring. I don’t know if that’s a good thing or a bad thing!
It’s probably a good thing. Maybe. I have found that dreams often reflect my state of mind in ways that I can’t always predict. But the two that you mentioned — with the Hitler dream, the feeling of this extraordinary technology that I had been involved in at the very origin and realizing the potential power of it and grappling with that. What does that mean in terms of my own responsibility? It was about struggling with that kind of question. Then with the tsunami dream: I grew up in Hawaii, and for me, the ocean has always represented an incredible source of inspiration and beauty but also great risk. I think about science in the same way. There’s so much out there we don’t know, and so many interesting ideas to pursue, but there’s also risk. There’s the mundane risk of maybe my experiment won’t work, but also the more profound risk of will I actually do something interesting with my life? Is this going to be an interesting way for me to contribute to the world?
Isn’t it safe to say you’ve answered those questions positively? [Laughs] Well, let’s just say it’s an ongoing project.
This interview has been edited and condensed from two conversations.
Opening illustration: Source photograph by Christopher Michel
David Marchese is a staff writer for the magazine and the columnist for Talk. Recently he interviewed Neal Stephenson about portraying a utopian future, Laurie Santos about happiness and Christopher Walken about acting.
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