Resilient Plants: Drought & Pest Resistance through Gene Editing with Dr. Voytas

Richard Jacobs: Hello, this is Richard Jacobs with the future tech and future tech health podcast. I have Daniel Voytas. He is a McKnight Presidential Endowed professor, director at the Center for Precision Plant Genomics. So Dan, thanks for coming. How are you doing?

Daniel Voytas:  Doing very well. Thanks.

Richard Jacobs: What do you do at the center? What are your goals there or some of the work that you’re doing?

Daniel Voytas: Right. So I’ve been working in my academic career in the gene-editing space, so we developed a number of technologies to alter the genetic code and we focused the use of the technology on plants. And so we’re trying to make ways in which to edit plant genes more effectively, more robustly, and then ultimately we want to use the technology to create plants with new traits, plants that better withstand drought or insect attack or produce healthier food.

Richard Jacobs: So are you focused on, I call them the common food crops, corn and rice and things like that, that affects millions and billions of people or which kind of plants are most amenable to edit?

Daniel Voytas: Yeah. So at the university, we mostly focus on a handful of model plants. Wild species of tobacco, Arabidopsis and we do that because those plants are easy to handle in the laboratory, we can execute experiments really quickly and test new ideas and new technological approaches. But almost 10 years ago, I started a company Calyxt which uses the technology in particular to create new crop varieties, soybean, and wheat. So it’s really an application of the tools that we developed at the university to create new food products, healthier food products. And that’s really the mission of the company to create healthier food.

Richard Jacobs: So why would you change the plant to make food healthier? Like what’s the criteria for that?

Daniel Voytas: Well yeah, I’ll give you an example. The first product we’ve created, and it’s actually the first gene-edited food product ever to enter the food supply. It’s an improved soybean oil. So conventional soybean oil is typically high in polyunsaturated fats. And in the past it was chemically treated, hydrogenated to make more monounsaturated fats so that it behaved better for food applications. But one unfortunate consequence of that chemical processing was that trans fatty acids were produced and in the past few years, they’ve been banned by the FDA from the US food supply. And so we use gene editing to solve this problem. So rather than chemically treating the soybean oil, we just edited the soybean genome so that it now made a much healthier oil. An oil that in which you can fry foods three times longer than conventional oil. And so just through a simple gene edit, we could convert soybean oil to an oil that has properties more like olive oil for example.

Richard Jacobs: Well, okay, so if you could fry it longer, what does that do? I mean, what happens to it if you fry in it? Does it degrade to produce unhealthy portions of it if it’s fried for a certain amount of time? Like what happens?

Daniel Voytas: So if it’s high in polyunsaturated fats and if you fry for a long period of time at high temperatures, it tend to polymerize the fatty acids tend to polymerize and make split a plastic-like substance. So the shelf or the fry life of the oil is reduced and hence the quality of the oil is less valuable. And so this way we can fry three times as long before that oil needs to be changed out. So, cooks and people who are in the fry food industry they love the product because they can use it much longer without having to discard it.

Richard Jacobs: Oh, I see what you mean. Can you say what’s being changed about the oil, to allow it to be used longer?

Daniel Voytas: Yeah, so we simply inactivated a gene in the soybean genome and this gene converts monounsaturated fats to polyunsaturated fats. And so with that gene inactive, the soybean seed accumulates monounsaturated fats and those are the heart-healthy oils and the oils that allow you to fry longer. So we just simply changed the way soybean seeds make fatty acids and hence the oil that’s produced from those seeds has a very different profile and in this case, a much better profile.

Richard Jacobs: How does that affect the planet itself? Does it affect its growth? I would think that it would have other consequences on the plant.

Daniel Voytas:  Yeah, it’s a really good question. And it’s something every time you carry out gene editing in a plant, it’s something you have to think about. Are there unintended consequences? So the gene we inactivated, there are several duplicate genes that makes these polyunsaturated fats and we inactivated two of them that are only expressed in the seed.

So the remaining genes are expressed elsewhere in the plant. And so in this case, we didn’t have any negative consequences for the plant. The plants grow and produce and yield the same as the unedited plants. And we just affect those genes that are expressed in the seed. So we just affected the oil that’s produced in the seed.

Richard Jacobs: I’m sure there are many, many, many ways soybeans are used, so not just for frying oil, but what other ways would it be affected positively for consumers?

Daniel Voytas: Well I mean, the way I sort of view, I sort of used soybean, if you will, as a chassis for creating a wide variety of oils that could have many different purposes. So we know the genes that make the fatty acids that comprise the oil. And so we can do editing. We can change the genetic code, change those genes in certain ways to give us different oil profiles. So you could imagine the first gene-edited product, is this healthier oil for frying? But maybe you could make soybean produce a substitute for Palm oil. Palm has desirable properties as a food ingredient, but of course, you have to produce it in tropical regions of the world and deforestation occurs in order to plant more Palm. So why not just make soybean a Palm oil substitute or a cocoa butter substitute or a wide variety of oils that we use as food ingredients on a daily basis. Gene editing is, I believe, is a powerful enough approach to enable that to happen.

Richard Jacobs: I mean, what oils are made from like a soybean base typically right now?

Daniel Voytas: So typically right now soybean grain is crushed to produce oil and certainly that oil is millions of metric tons of that oil are made annually and it’s used in a wide variety of food ingredients. We just for certain applications like frying, we just created a soybean variety that would make a better oil for those purposes. So as I mentioned earlier on in the past, soybean oil was chemically treated to achieve these improved properties. And with the FDA requiring that foods that have trans fatty acids be labeled and then ultimately banning foods with trans fatty acids, food manufacturers turned to canola oil or sunflower or other types of oils that would give them to properties that once upon a time the chemically treated soybean oil provided. So we just gave soybean genetic attributes that would allow it to produce now that better oil if that makes sense.

Richard Jacobs: Okay. Yeah, I understand. All right. What other modifications are you looking at doing? So you have soybeans and like you said, they’re very versatile. They’re like a chassis. What else?

Daniel Voytas:  Yeah, so the next crop that we’re working on is wheat. And so there, I view wheat as a chassis for carbohydrate production. So our first product in wheat will have higher dietary fiber. And so the idea is that if you eat a sandwich made from flour from our wheat variety, you have a much better chance of meeting your daily fiber requirements than if you ate a sort of conventional wheat flour. So there again, we’re using the editing technology to create a healthier food ingredient.

Richard Jacobs: Oh, well specifically with wheat. What are you working on doing?

Daniel Voytas: So there were just changing the starch composition. We’re making starch so that it’s less readily digested by our body and therefore when it’s digested, it’s broken down into simple sugars. And those simple sugars are then used as a source of energy.

But if you change the starch and the structure of the starch so that it’s broken down less readily than it serves as a source of dietary fiber. So that’s an example in wheat. So our business is a little unconventional. So in Minnesota where the company’s located, we create these crops varieties, but then we contract with farmers in South Dakota and Minnesota, North Dakota, Iowa, to grow our varieties for us. And then we buy back the grain they produce and then process it into the healthier food ingredient. So we’re a company that uses gene editing to make the food ingredients and actually produce and sell the food ingredient in the end. And so I talk about soybean and wheat because our South Dakota partner farmers, they grow soybeans and wheat. And so we are focusing on the crops that are producers, mainly the farmers grow in those geographical regions. But we’re working with other companies and other entities to make other types of crop varieties that produce different food ingredients or enhance the sustainability of agriculture.

Richard Jacobs: Well, okay. So in the changes that you’re making, have you seen that you’re able to isolate genes and make changes that don’t affect the rest of the plant or the rest of the foodstuff? Has it been tricky? Have there been dependencies?

Daniel Voytas: Yeah, it depends on, you know, it’s sort of a trait by trait, gene by gene. It depends. I mean we’re focusing on pathways, metabolic pathways that are pretty well understood. Fatty acid biosynthesis, starch biosynthesis, for example, carbohydrate biosynthesis. But biology, there’s still a lot to be learned and sometimes you inactivate a gene and you’ll find it has some other unintended consequences, maybe reduces yield or maybe reduces yield at certain temperatures when it’s grown. And so we have a rich pipeline of traits that we’re developing and because there are some uncertainties in our understanding of biology.

Sometimes some of the product concepts fall to the wayside because we make that it and it had unintended consequences. And so it was not an ideal product candidate after all.

Richard Jacobs: Looking at yields or is that a whole other area that is a whole other can of worms?

Daniel Voytas: Well, it is a whole other can of worms, but I think gene-editing technology can be applied far beyond making healthier foods. So pest and pathogen resistance, drought tolerance all of those I believe can be improved through the use of gene editing. As I said, fatty acid biosynthesis and carbohydrate biosynthesis we really understand the genes that are involved in those processes, but when you talk about yield or pest tolerance or drought tolerance, there are many different genes that work together to confer those traits. So we still need to learn a fair bit more about the underlying biology of how those genes contribute to those traits and promote yield. But then ultimately I think we will be able to use the gene-editing technology to confer those types of traits.

Richard Jacobs: In speaking to other plant people over the years, I guess the average at least the photosynthetic efficiency is like 1% from any plants and the superstars of the plant world are 2 or 3%. I don’t know how that translates exactly the yield. How you would express the yield, I guess currently, let’s say for rice or wheat or soybeans or corn?

Daniel Voytas: It’s usually the amount of grain produced per unit of land acre, hectare, for example. So that’s typically how yield is calculated. But you alluded to photosynthesis. There’s a lot of amazing, incredible work being done right now on making photosynthesis more efficient. And the consequences that yields increase, the amount of grain you can harvest per acre can increase, the biomass amount of vegetative material produced on an acre of land can increase if photosynthetic efficiency is increased. And those technologies require in many cases or benefit from gene editing, so you can go in and make the tweaks that will allow you to be more productive and allow the plant to be more productive.

Richard Jacobs: What about doing this to hybridization? Are there any other strains, let’s say, of corn or soybeans out there or other plans that you can hybridize these with and maybe accomplish the gene editing in a different way? Or is that much sloppier and this is more precise?

Daniel Voytas: I’m glad you brought that up because that’s the conventional way we’ve created new crop varieties. We cross different varieties that have different traits but in a breeding program what you’re doing is you’re combining genes from two varieties in different ways. And you’re hoping that some combination will improve the plant for whatever traits you’re interested in. But that’s an inherently kind of random process and not well controlled. Sometimes it’s just serendipitous if you land upon the right combination of genes that give you the traits are after let’s say improved yield. Gene editing is sort of different in the sense that we start off with the hypothesis at least that we know if we tweak certain genes in a certain way, they’re going to give us a desired outcome. And again, you alluded throughout this conversation that sometimes we’re wrong, but as we increasingly understand about how plant genes work and function we get better and better at predicting which genes and which genetic alterations are going to give you an improved plant. So I think it’s a nice comparison to the sort of the random stochastic process that takes place during breeding as opposed to the more precise focused and directed approach of gene editing.

Richard Jacobs: What about pest resistance and resiliency of let’s say that given the field, have you looked at possibly doing gene editing so that you produce extremely similar but different types of let’s say corn plants so that you can plan a field and have maybe 10 different types of corn even though they’re almost all exactly the same, but they’re different enough so that pests wouldn’t destroy the whole field. They’d only destroy certain ones or certain ones would be resistant somehow or have different phenotype that would be resistant to an issue that would normally wipe out the whole field.

Daniel Voytas:  Yeah. It’s a really interesting point because typically what’s done now is you have thousands of acres planted with a single variety, right. And that does present an inherent risk if that variety is susceptible to a particular disease or new pester pathogen enters the geography where that particular variety is being grown. So we can certainly use gene editing to create a whole array of plants that are resistant to different pests and pathogens. The flip side of the coin though is that then you need farming practices that would incorporate that genetic diversity that we create. And so it’s certainly doable and an approach that can well be undertaken.

Richard Jacobs: Yeah. I guess if you get good at tuning it, good enough, and you’re precise enough, then to the eye everything would look maybe the same, but to the appetite of a certain pest, let’s say, will look different.

Daniel Voytas: Very different. Yeah.

Richard Jacobs: Any moonshots or things that are tough problems so far, that you’re working on?

Daniel Voytas: Well, I focus a lot and this is circling back to my work at the university. We focus a lot on improving the technology and making it more efficient and easy to edit plant genes. And so right now we’re kind of in the era of editing one or a few genes at a time, but kind of getting back to the, you know, you were talking about comparing and contrasting to breeding. When you cross two plants you’re mixing the genotype of the two parents. So the progeny has a wide variety of genetic variation, a lot of different gene combinations that are put together. And so we’re working hard now on moving gene editing from altering one or a few genes at a time to maybe altering the hundreds or even thousands of genes simultaneously. And so then you can really think about not just changing the fatty acid composition of that soybean, our first gene-edited product, but the fatty acid composition of that soybean, making it resistant to nematodes, pests and pathogens. Making it possible to grow in new geographies or under on marginal lands or places where the season is particularly short as he moves North with swiping to Canada for example. So over a few year span, we can create a new soybean variety that has a few altered genes, but it’d be great in a few years span, make a soybean variety that has many genes and many new and improved attributes.

Richard Jacobs: Well also too, I would assume this happens in plants, but epigenetic effects based on season, based on the plan doing what it does that you somehow cataloging mills. You make a change to a gene, you add remove ever just changing an expression. But then the epigenetic effects kick in the adaptation, it goes through the hot season, the cold season, whatever it is. How do you know what’s going to happen to the changes you make and how they’ll come out in the wash? I guess mixed metaphors.

Daniel Voytas: Well, I mean at this stage of the game, I mean myself and many of the people working in gene editing are mostly focused on altering the genetic code. Now as you suggest, some of those alterations can have consequences for the epigenome. And some of my colleagues are actually working on making directed modifications to the epigenome, changing DNA methylation patterns, for example, which can change gene expression. So that’s kind of a, I would call it a new frontier is a sort of editing the epigenome. But most of what we do now change the genome and then when we see a phenotype of consequence for changing the genome, we’ll look at how that change came about. Did we alter expression of the gene, did we inactivate a gene or did we change the epigenetic landscape around that gene by changing the DNA sequence? So all of those are kind of possibilities.

Richard Jacobs: Okay. So what do you see as the future for your work? Over the next few years. What would you love to see happen?

Daniel Voytas: Well, I feel very fortunate and because I have two jobs really, so at the university we develop new technologies, we improve the technologies. I work hand in hand with colleagues all around the world who have the same ambition and you’re continually learning. Science is moving at a really rapid pace. So there’s an underlying biology that we’re learning all the time and trying to understand how to harness that new information and apply it to improve gene editing and then I go to the company that I helped found and there I can see, take the state of the art technology and see it being realized into creating healthier food ingredients. So I feel very fortunate to keep abreast and to participate in the advancement of the science, but then also to go to the company and see it developed and applied and to create. In the case of Calyxt and its mission, healthier food ingredients.

Richard Jacobs: Are there any dream foods that people have been talking about altering for a long time that has been out of reach for some reason?

Daniel Voytas: Well, I think an interesting area that we’ve gotten increasingly involved in is, we call them orphan crops. Like soybean and corn and wheat. They’ve been the subjects of intense breeding efforts over the years and dramatic improvements have been seen in yields and productivity. But I have a graduate student who was born in Ethiopia and her grandfather farmed this grain called Teff which is a staple of Ethiopia and the countries of Eastern Africa. And the varieties of Teff that they grow are really wild landraces. And so she’s come to my lab because she wants to use gene editing to introduce a few traits that could really have remarkable improvements in the production of this crop. So it’s tall and lanky and it falls over and a lot of the seed is lost. So she’s interested in making semi-dwarf varieties of tests that would hopefully produce more and be easier to harvest as one example. So, I think there’s a lot of opportunities. That’s just one example. There’s a lot of crops, from vegetables to grains to fruits that have not really been subjected to intensive breeding efforts and gene editing. Now that we understand a lot about how plant genes work and function, gene editing can be used to improve those sorts of orphan crops very quickly, very dramatically and increase food security and the food supply, I believe.

Richard Jacobs: Well, very good. Well, Daniel, what’s the best way for people to find out more about what you’re working on and possibly get in touch?

Daniel Voytas: Well, I think the easiest way is just to send me an email at my university address voytas@umn.edu and also I have a website of course at the university that provides some contact information.

Richard Jacobs: Okay. Well, excellent. Well Daniel, thanks for coming on the podcast. I appreciate it.

Daniel Voytas: Yup. Appreciate it. Thanks for the invitation.