The CRISPR Revolution: Chancellor Woodson Talks Science and Innovation with Professor Rodolphe Barrangou

CRISPR has the power to correct genetic diseases like sickle cell, or change the fiber content in trees to make them more amenable to processing. Rodolphe Barrangou, a pioneer in the discovery of CRISPR, joins Chancellor Woodson at the Plant Sciences Building to discuss this revolutionary technology in this episode of Red Chair Chats. Barrangou, the Todd R. Klaenhammer Distinguished Professor in the Department of Food, Bioprocessing and Nutrition Sciences at NC State University, was inducted into the National Inventors Hall of Fame in 2023.

You can hear an audio version of this conversation on the Red Chair Chats podcast, available on Spotify and Apple Podcasts.

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Transcript

Chancellor Woodson: Hello, Wolfpack family, and welcome to another episode of Red Chair Chats. You know the drill. This is where we get together with famous faculty, alumni and friends of the university. And today you’re in for a treat because embodied in one person, we have all three of those categories: faculty, friend and alum of this great university. So today you’re going to hear from and meet, maybe for the first time, Rodolphe Barrangou, a professor here at NC State University, proud to be at NC State, one of the co-discoverers of the CRISPR-Cas system. And I’m going to have Rodolphe tell you all about CRISPR, but this is an amazing scientist. And I know when I think of CRISPR, I think about the drawer in my refrigerator where I keep lettuce and other things that I want to be crisp, but today we’re going to learn more about all the technology and the biology around CRISPR. So welcome, Rodolphe.

Rodolphe Barrangou: Randy. Good to see you. Glad to be an alum, a friend and a distinguished professor, allegedly. CRISPR is amazing. It’s one of those things that changes the world. It’s an amazing technology that allows us to rewrite the genome and do genome editing. And we stand at a time now when we can use CRISPR technology to rewrite the genome of virtually any species on planet Earth to do anything we want, anywhere we want, for anything we can think of.

Chancellor Woodson: It’s a lot of power in your hands. But let’s talk. Let’s go back in time. As I said in my short introduction, Rodolphe is a distinguished professor at NC State. He occupies the Todd Klaenhammer chair in probiotics research. Many of us know about probiotics. Those are the good organisms that inhabit our gut and help us with digestion and nutrient absorption. But let’s talk about CRISPR. Let’s talk about how you and your colleagues came to discover the utility of what is really an adaptive bacterial immune system. So tell us, what is CRISPR?

Rodolphe Barrangou: So CRISPR is an acronym that stands for a mouthful: clustered regularly interspaced short palindromic repeats. Nobody really cares, to be honest. What’s really interesting is that in nature, CRISPR is present in about half of all bacteria on planet Earth. And we discovered in your good bacteria that this system allows those organisms that make, turn liquid milk into yogurt or cheese, it allows them to be resistant to viruses that infect them, called bacteriophages or bacteriophages, since I used to be French.

Chancellor Woodson: He’s not from America, but he’s been here for a while, so I’ll interpret for you. On you go.

Rodolphe Barrangou: Thankfully. And those bacteria get hammered all the time by viruses. And they’ve evolved over time, a complex molecular system that allows them to specifically cut DNA of invasive genetic elements. And the team that I worked out at DuPont, which makes, by the way, yogurt starter cultures for half of the world, we were able to show that this idiosyncratic, peculiar DNA system allows them to cut phage DNA. And subsequently this ability, this natural ability to act as a molecular scissor, was used to cut DNA in other species like humans to address genetic disease, like crops and plants to address climate change, and drought, and heat, and pests, also in cattle to make them more resistant and more resilient to viruses in the environment, and even in trees here on campus to provide more sustainable forestry. So we now have a molecular tool that allows us to rewrite DNA and species of interest to us to make things more sustainable, more healthy and more efficient, but it all started with food. And you never know where things are going to take you. You have to start somewhere and let science and technology unfold as they may. And we have a great legacy at NC State in doing that, from the great late Todd Klaenhammer, to the great expertise that we have in food science and nutrition. And of course the College of Ag and Life Sciences, which historically has been a pioneer in breeding plants, breeding livestock, and we can now use those technologies for all kinds of applications.

Chancellor Woodson: Well, let’s go back even further in time. As a young man from France over 20 years ago, you came to the U.S. to NC State to study under Todd Klaenhammer. And so talk about what drove you to want to come to NC State and how as a two-time alum of this university, this education and this environment is translated into what you’re doing now.

Rodolphe Barrangou: I mean, born and raised in Paris, big city, millions of people, busting life and business and the like.

Chancellor Woodson: Similar to Raleigh. I mean…

Rodolphe Barrangou: I always wanted something enjoyable, quality of life, something that was more adventurous, more original, more innovative, more disruptive. And I remember the first time I came to Raleigh coming out of Terminal 3 in RDU when it still existed and smelling the pines, smelling the trees, feeling at home when I had never been here before. And little did I know 26 years ago, I would spend the bulk of my life here, meet my wife here. She’s an alumna as well at NC State, twice over, master’s and Ph.D., and it was life-changing. What I learned here, the Think-and-Do attitude, the great faculty, the great ingredients that we’ve collected to transform the lives of our students, and our staff, and our colleagues, and our stakeholders, and our partners is just unbelievable. 

And the preparation that we get in the classroom with real life skills, not just think, not just abstract, not just fundamental, but also applied real, legitimate, innovative, disruptive, and translational is what, when I graduated, got me to move to Wisconsin for nine long winters. And after nine long winters in Wisconsin, I knew I wanted to come back home for climatic, cultural, business, professional, and a sense of belonging, purpose.

And much like I wasn’t born here, my kids weren’t born here, this is home. We have so many things to offer to the world and so many grand challenges that we’re trying to address institutionally inside NC State and outside of NC State with our partners in RTP, local and international, that we have the ingredients that we need for a masterpiece.

Chancellor Woodson: Well, getting back to CRISPR, one of the things that I know about you, in fact, the first time we met, I recall walking across campus and being introduced to you as a new professor at NC State, a returning alumnus of the university, and you said CRISPR is going to change everything. And boy, were you right. So talk about innovation. I mean, last year I had the honor of being your guest in Washington when you were inducted into the Inventors Hall of Fame.

And for those of you that don’t know what that is, that’s the U.S. Patent Office that has a hall of fame dating back to Edison and so many other inventors. And Rodolphe is one of five or six faculty members from NC State that have been inducted into the National Inventors Hall of Fame. And so talk about, I know behind us on the wall, there’s CRISPR Journal. You’re the editor of a journal devoted to this science. Your license plate, even today in North Carolina and back in the day in Wisconsin, has “CRISPR” on the license plate, so you’ve been all in for a while, but talk about how, I mean, you founded, gosh, how many companies now? Five companies, multiple, over two dozen patents. So talk about how CRISPR is translating into economic vitality and prosperity. Not just scientific prosperity, but economic prosperity for our globe.

Rodolphe Barrangou: So often you don’t realize you’re in the middle of revolution until after the revolution is over. And I had the privilege to have a front seat to the CRISPR revolution. I played my role in the development of the technology, for sure, and what I essentially consider myself as a translational researcher, and the hard part is to translate fundamental science into useful technology that can be applied to develop products. It’s very hard to do that. We have a lot of great scientists. Sometimes we have a great commercialization team, a manufacturing team, but it’s very hard to be able to play a role in the true translation of science from early discovery to real products.

Chancellor Woodson: They don’t talk the same language.

Rodolphe Barrangou: They don’t. They don’t oftentimes have the same skills either, or the same drive, or the same motivation, or the same skill set. And very early on I realized that CRISPR, though it was scientifically interesting, it was technologically very practically useful. And I run the CRISPR lab at NC State, we train students and talent and bestow upon them skills in the classroom and in the lab, undergraduate and graduate school, to prepare them for careers and life sciences and beyond.

But we also spend a lot of our time taking that technology to our partners and stakeholders, work with industry. And the industry has an impetus to commercialize great technology to develop great products. And CRISPR is one of those technologies that is very practically relevant. And we’ve worked with startups in the therapeutic industry, including Intellia, ringing the bell at the Nasdaq with the team, where we can use the technology to correct genetic disease in patients that are afflicted with genetic mutation. We also work with-

Chancellor Woodson: Make that real. What’s an example of a genetic mutation that results in a disease?

Rodolphe Barrangou: So someone has sickle cell. They have a genetic disease, they have one mutation in one gene that impedes their ability to consume oxygen correctly. And it’s painful and it’s life-altering and life-shortening. We have the ability with CRISPR molecular scissors to go into their DNA, target the gene that is faulty, specifically cut the gene at that location and correct the genetic disease, and restore the wild-type phenotype where they have a normal life. One single dose, and they’re corrected for the rest of their lives.

What sounded like science fiction just 10 years ago is now a medical therapeutic reality and it took the team maybe collectively about eight years to dose the first patient, another year to dose 10, another year to dose a hundred. And this year we’re going to dose a thousand people. And you can see how quickly and how readily those technologies can allow us to correct genetic disease.

Now you can take that same technology outside of human therapeutics, let’s say agriculture, huge industry in North Carolina, and we can use that same technology to enhance the genetic content of crops to make them more resilient, to make them more resistant to pest or drought or heat or chemicals, and allow us to breed more sustainable crops and use the same technology and implement it in livestock to breed more sustainable livestock.

Chancellor Woodson: So Rodolphe, not to get too technical, but I know many of our listeners really understand genetic modification. When you think about, you go to the supermarket today, you see a product that says GMO-free genetic modification of the organism, but CRISPR is very different. CRISPR is not inserting new genetic information. It’s modifying existing genetic information. And so it’s regulated differently. Talk a little bit about the unique opportunity that affords a field like agriculture.

Rodolphe Barrangou: Correct. So most of the users of CRISPR are not transgenic. We’re not taking DNA from one species and transgenically putting into the other. What we do is we can accelerate, and speed up, and ease up, and lower the activation energy and the cost of being able to take the best traits within one species. Corn, soy, tomatoes, whatever food vegetable you like the most.

Chancellor Woodson: I had some raspberries this morning. That would be more difficult, but…

Rodolphe Barrangou: We actually work on berries too, so very, very fitting. We have colleagues just down the street door that do do that, and we do have berries upstairs actually in our greenhouse. And we can take that CRISPR technology in combination with our understanding of genetics and what we know lies into the genetic pool of the species to breed it in. And we are replicating what would happen or occur naturally. We just make it easier, faster, and more efficiently. And rather than take years to accidentally breed one great genetic trait into one great, commercially relevant early germplasm, we can take that sequence of interest in the species and use CRISPR to breed it into the germplasm of interest.

Chancellor Woodson: Well, so you’ve taken on now with your colleague here at NC State, Jack Wang, really one of the most challenging species known to man in terms of being able to modify the genetics of a species. You’re working on trees; long-lasting, long periods of reproduction. So talk about tree genetics and how CRISPR is now being used to modify something as important to our world as trees.

Rodolphe Barrangou: So with great expectations and great possibilities come great responsibilities. And we have a duty in many ways collectively to use the best science and technology in the world to address the greatest challenges. And trees unequivocally comprise and constitute about 75% of all carbon and planet Earth as a living entity.

Chancellor Woodson: 75%.

Rodolphe Barrangou: 75%. So if we want to make a difference there starts and it ends with a tree.

Chancellor Woodson: Plant a tree.

Rodolphe Barrangou: Or two, or 10. So we have the aspirational responsibility, so to speak, to use CRISPR in the context of free genetics to breed a healthier planet. And it’s challenging because it’s difficult, it’s slow, it’s not very popular, it’s not very easy to fund, but it’s transformationally set to have a huge global impact on carbon capture. And if we can use CRISPR to breed a better and more sustainable forest, we have a responsibility to do so.

So thankfully at NC State, we have faculty, we have knowledge, we have expertise, we have know-how, we have students, we have partners and stakeholders, very aware and expert in the forestry business. And we’ve been able to collect all those ingredients to bring CRISPR to forestry. And as a matter of fact, remarkably, in just five years, we’ve been able to not just do it, but also take it far enough to actually plant the first trees in a field trial. And this is the beginning. We’re literally ushering in a new era of sustainable forestry by using CRISPR to breed better, more efficient trees.

Chancellor Woodson: And what would be a trait, an early target in trees for CRISPR modification? I think I know, but…

Rodolphe Barrangou: Trees are very important for many, many products that we use. Paper, toilet paper, tissues, feminine hygiene products and the like.

Chancellor Woodson: You see, you didn’t think we were going to talk about toilet paper today, but this is Red Chair Chats. We cover all subjects. On you go.

Rodolphe Barrangou: It’s a very big deal. It’s very useful, it’s very useful. We can’t do without it.

Chancellor Woodson: Got to have it.

Rodolphe Barrangou: You just got to have it here. So unfortunately, it’s very inefficient to turn hard wood into soft toilet paper. It takes about two tons of wood to make one ton of toilet paper. We can use CRISPR to change the fiber content and the fiber composition in trees to make them more amenable to processing. It’s going to take us less time, less energy, less money, less resources, less chemicals and less industrial output and input to generate the same amount of toilet paper or tissue.

And this is just the beginning. Right now we’re changing the structural fixtures, the malignant content in trees to lower this to some extent, and then improve the chemistry in order to make it more efficient to break it down. But that technology can also be used to do other trades. So making sure that wood is sustainable, making sure that wood is resilient, making sure that we can culture and all grow forests in parts of the world where the environment is changing. Make sure that they’re more resistant to pests and insects, not just weather, and then change some of their properties so we can use wood in other applications. So think more sustainable and efficient furniture, more sustainable and efficient paper, more sustainable and efficient biofuel and all the products derived from forestry.

Chancellor Woodson: Wow. So when you were back in the lab in Wisconsin, those cold winter nights, working on yogurt and working on the bacteria that are so critical to convert milk into yogurt, did you imagine everything that would come out of some of those early discoveries in CRISPR-Cas system?

Rodolphe Barrangou: Hell no. Right? Not even close, right? I mean…

Chancellor Woodson: Well, I find that hard to believe because you’re always thinking about the future, but…

Rodolphe Barrangou: Well, you have to think, right?

Chancellor Woodson: And do.

Rodolphe Barrangou: You have to think and you have to do, evidently. I think you have to be innovative and disruptive and kind of forecast, anticipate or create a future out there. But until you do it, you’re not sure it’s feasible, you’re not sure it’s achievable. And if you’ve done it once or twice, then you build an appetite to do even more with even less. Go farther. Go faster. And to be honest with you, I always had the assumption that we were going to do something that was going to be impactful, transformative, disruptive, innovative and translational, but I had no real idea of how far and how fast we will take this technology.

And when I came back to NC State after nine long, painful winters in Wisconsin, I’m never going to shovel again in my life, for sure. Mark my words. We can now say we’ve used and developed technology that has dosed patients down the street. We’ve developed technology that we’ve planted in a field, we’ve developed technology that was used to breed a tree that is now growing somewhere in the forest. And I didn’t know how far we were going to take that. I didn’t know maybe how hard it was going to be. But thankfully we have the environment, we have the people, we have the colleagues, we have the students, we have the partners, we have the stakeholders, we have the leadership that allows us to achieve all those things.

Chancellor Woodson: Well, and we’re in the Plant Sciences Building, one of our newest buildings on Centennial Campus, and Centennial Campus has afforded you and the companies that you’ve built an opportunity to grow those companies, an opportunity to interact with colleagues. There are over 70 companies that call Centennial Campus home. So the innovative environment that you and so many others before you have built on Centennial Campus is another feature of, I hope, one of the things that brought you back to NC State.

Rodolphe Barrangou: So one of the things that brought me back to NC State, one of the things that makes me happy at NC State, one of the things that make me stay at NC State, and commit to NC State long term as an alum, a friend and a faculty member, is our commitment to entrepreneurship. The award right in the back right here is an entrepreneurship award by NC State that you…

Chancellor Woodson: I just handed it to you not long ago.

Rodolphe Barrangou: Absolutely, right, and it means a lot to me. I mean, notwithstanding my scientific accolades, being an entrepreneur and being able, within the university, to foster research and innovation that can have a translational impact matters substantially. And having buildings of the Plant Sciences Building, having the office of research commercialization that we have, which aggressively not just builds the IP and develops the IP and patents, the IP, but licenses it and brings it to the world and shares our sense of urgency for translational research and commercialization is a huge difference maker.

And one of the most enjoyable adventures I’ve embarked on, notwithstanding the science and the education and teaching and research, is actually building companies as a founder, an innovator. And we have so many companies, including some here that I’m on the board of, a founder of, even an investor in and a partner of that are changing the world because places like Centennial Campus, universities like NC State, entrepreneurs, founders, students, colleagues that can all kind of meld together in a business masterpiece that can execute on an ambitious vision, that can bring in the capital that we need to do it and take it to reality, however hard that may be, it’s even more enjoyable.

And having done it multiple times, you build an appetite for more and you know how to do it, what mistakes you can make, afford to make, what things you’ve got to change, what things you got to do better or faster. And we have unquestionably all the things that we need right here, right now at NC State, on Centennial Campus in the Plant Sciences Building to unleash the innovation power that you have and the potential that we have in agriculture and more.

Chancellor Woodson: Rodolphe, today, I’m sure we have some young people, maybe high school students, even middle school students, and certainly undergraduates at NC State that might be watching today’s program. What advice would you give them about what they should be doing, thinking about, to be prepared for this new world of science?

Rodolphe Barrangou: A couple of things. So first, you have to be curious and you have to allow yourself enough room to be curious. What do you want to learn? What are you interested by? What are you curious about? What questions do you ask? How does this work? What does this do? How can you use this to do that? I think you have to give yourself some room to kind of explore and be mindful and be curious and be adventurous and innovative. Give yourself room to grow and develop.

Another thing that’s very important for young people is you have to learn to learn. The world is changing so fast. Science, technologies, machine learning, AI, big data, statistics, you’re going to have over the whole course of your life to learn to use new tools, learn to use new toys, learn to iterate things and use machines or technologies that don’t even exist today, just to make it and move forward. So you have to learn to learn, you have to learn to adapt, you have to learn to be flexible.

And then last but not least, if you do something interesting, it’s going to be hard. And you have to learn to fail and accept that. You have to build an appetite for hardship and be resilient because regardless of the job you’re going to have, if you do things that are interesting and valuable and impactful, it can’t be too easy. And you have to kind of welcome the challenge, rise to the challenge, and build appetite for competition. Whether you compete with yourself, you compete with others, you compete with your siblings, you compete with your parents, you compete with your colleagues, you have to learn to take you to the next level, pick yourself up, move on, and do it again.

Chancellor Woodson: Yeah, great advice. Great advice. Great example of Think and Do.