33. Purple Reign, A Purple Tomato with a Genetic Twist, Nathan Pumplin of Norfolk Healthy Produce

[00:00] Speaker: When you talk to people who say, "I don't like GMOs, I'm really against that, I think it's bad," and you ask them why, and then you start to talk to them about, "Well, you know, we made this purple tomato. It uses transgenic technology, but it's putting a gene from an edible flower into this tomato to turn on a natural pathway. It has these nutrients that are in blueberries and acai berries and blackberries." People say, "Oh, that's really cool, but I didn't think GMOs did that." I love having this conversation because I can say, "No, our product isn't any of those things." And almost universally people say, "Okay, well, yours is a GMO I can get behind. This is something I really want. I can't wait to have it [00:37] Speaker 2: Hey, Carl. How you doing? [00:38] Speaker 3: Hey, Rem. I'm doing great. How about you? You've had a very eventful week, and we were gone for a week, so I think there's a lot to catch up on [00:45] Speaker 2: Yeah, I know. It's been a bit chaotic for me and my travels. I mean, the actual traveling to Ontario, Canada, for my husband's cousin's wedding, big Indian wedding, so lots of parties four or five days in a row. It's exhausting. So I was really looking forward to coming back. I was coming back Sunday, but then our flights were canceled and they were canceled for, like, inclement weather, which was storms, and I know those storms resulted in floods, so we ended up getting tickets back that Tuesday. And what happened was, I mean, this is a public service announcement here, is that if you're flying anywhere, make sure to check in 24 hours beforehand because if flights do get canceled, then you can rebook, like, the next day instantly. We didn't check in until, like, a few hours beforehand, and then we found out, and then we couldn't get any flights. They were all booked up until Tuesday. So we had two extra days in Canada, but we made lemonade out of that lemon, and we had a little bit of vacation, but trying to work the challenges that I had my toddler with me. So, like, I was day caring it, trying to talk to you, Carl, about things. And needless to say, I'm happy to be back. I'm happy we have daycare. Thank you to the daycare teachers for taking care of him. You're so appreciated to me because now I can have this call with you, Carl, without a baby screaming in the background. [01:53] Speaker 3: Well, and I never mind the baby screaming in the background'cause he's never really screaming in the background, and I've lived through that, so I know it very well. So we had Canadian fires in May, June, where that turned the sky orange. We've had the hottest day in history just a couple days ago. It's been, like, 100 degrees above the Arctic Circle, so the weather's crazy. I read a long piece by Mil- Bill McKibben in The New Yorker about how we still continue to invest in fossil fuel infrastructure even though the world's on fire. Vermont, where he lives, has been declared a natural disaster because of the flooding there. I was lucky to make it back from the Adirondacks on Amtrak, I think, last Saturday or so. But it was still, like, a bit of a pathetic experience because Saratoga Springs to New York City is typically a three-hour train ride. It took about four and a half hours'cause there was a bridge up, and then the subway in New York was delayed, so it took me another hour to get home. So it was not that pleasant. I know that it takes eight hours on Amtrak to go from New York to Vermont. That should be a 90-minute trip. New York to Boston is a four-and-a-half-hour trip on Amtrak. It should take less than 90 minutes. The infrastructure is pathetic, and I'm hoping that given the climate emergency, some of that stuff gets taken care of. But I'm glad you're back. I know you're also leaving again to, what, a girls' weekend? [03:11] Speaker 2: Yeah. What's up? Shout out to my Delta Phi Epsilon sorority sisters who I've been friends with since college. I am taking the Amtrak to Lancaster on Thursday. One of my friends lives around there, and then we're gonna drive up to the Poconos. One of my friends has a lake house there. But hopefully, I get there in one piece. A lot of my friends are teachers or they work in another aspect of business, whether it's recruiting or real estate, and I was the only one of our friends that was really deep into the sciences. I was the only one that was a chemistry major, a forensic chemistry major in my group of friends. Actually, not just my college friends- But even up to this day, I, I haven't met another forensic chemist that I'm really close with. Aside from that, they always ask me like, "What are you up to?" Because I have had a very different career trajectory, where I was in the lab for several years, and then I was an entrepreneur, whether it was working at a startup or starting a company. So I've been doing many different things. So they always ask me, "What are you up to?" So I wanted to tell them about Messaging Lab, our podcast, biotech, and what I really want to ask them about is GMOs. What's the first thing they think of? I am in my 40s. We grew up in the'80s and'90s, and GMOs were something that came up, so they might have a different idea of it because of what was being said in the media about genetically modified organisms, whether it was corn or tomato. I know we'll be getting into that topic more. [04:32] Speaker 3: Yeah, I mean, I think career trajectories are very interesting. I think they've changed a lot. I've been an entrepreneur for, I don't know, a long time. It feels like a long time. And now that Alejandro, my oldest son, is out there looking for a job, I think a lot about how I got the jobs that I had, how I started Messaging Lab, how different people I know have gotten jobs, and how different it is, and how to help him and help people like him who are looking to get employed. So I think it's fascinating to think about when you're around people who are not entrepreneurs, which is already like a very different kind of space because, number one, it's very lonely, and number two, when you're in that space, it feels like... I mean, for us, we're around startup people all the time. We're around investors. We're around people who are really pushing technology forward, and we've done it both on the digital health side and in the biotech industry. So we see a lot of entrepreneurs. We see... We live and breathe entrepreneurialism. But if you're not in it, you just have no idea what that is, and I think it can seem very strange to other people. It's lonely, it's scary, but it's also the most exciting, invigorating thing in the world to be involved in. So I think the GMO question I think is really important, and I think it'll be interesting to hear what they say. What I'm gonna do is before I leave here today, I'm gonna make sure that when I see you this afternoon, I give you one of Polybion's wallets so that you can have that with you to show off to your girlfriends and ask them if that changes their perception of GMOs. Since we're talking about GMOs, or genetically modified organisms, let's use that as the segue into the introduction with this interview. Unfortunately, you weren't a part of this interview, Iram. I think that our listeners should get used to th [06:22] Speaker 2: Yeah. I first met Nate at SynBio Beta, and he presented his purple tomato. And I actually was introduced to the purple tomato at Ferment. They had purple tomato there. But at SynBio Beta, Nate rolled up with purple tomato salsa, and it was delicious. It was a deep royal purple color. Like, there's some heirloom purple tomatoes, but they're like the light purple. This was like a dark purple, and I was like, "Wow." It's so eye-catching, and it was delicious. And we had friends from all over that were trying it that are in our biotech community, people from Mexico that were like, "This is really good salsa." So hats off to Nate and his team for whipping that batch up. So I'm just really excited to learn more. I'm sad that I didn't get to talk to him. He has a really great personality. That's the type of person that you wanna be friends with, and you guys will understand what I'm talking about when you hear this interview. [07:08] Speaker 3: Our friend from iGEM, Daniel Dominguez Gomez, lives in Mexico City. Daniel said that it was the best salsa he had ever tasted, period. So coming from- Wow a taco expert from Mexico City, I think that is an amazing sign of greatness. So let's get into the interview. Hey, Nate. Welcome to Grow Everything. How are you today? [07:31] Speaker: I'm doing great, Carl. How are you? [07:33] Speaker 3: I'm pretty good. I think you guys have some exciting news, so why don't we kick off the podcast by talking about the relationship between Norfolk Healthy Produce and the FDA. What's going on there? [07:43] Speaker: Happily, Carl. Well, we just made an announcement yesterday. Of course, we've had this scheduled for a while, so the timing is fantastic, that our high antioxidant purple tomato product has completed their review with the Food and Drug Administration, and this is coming on the heels of our regulatory decision back in September from the USDA, and it gives us full green light to commercialize our product. [08:05] Speaker 3: So what does that mean? I mean, it's interesting because, like, the USDA, two weeks ago, approved these new cultivated chicken products, which I'm very excited about, and we've had some people on the podcast talk about that. But I haven't heard of any products like yours being approved in the recent past. Why don't you describe what the path to regulatory was and what does it really mean for you guys? [08:26] Speaker: Yeah, absolutely. So one of the main differences is we are working with a biotech crop product, and so this is different from a food ingredient or something that's purified. The regulatory process in the US is what's called the coordinated framework, and this dates back to 1987 when we knew much less about biotechnology and there were a lot of open questions. The coordinated framework works between the Food and Drug Administration, the United States Department of Agriculture, and the EPA, Environmental Protection Agency, and they regulate different facets of engineered crops or biotech crops. The USDA is looking at what's the plant pest risk. Is this something that could take over crops and become an invasive weed? For instance, could this have an impact on pollinators, et cetera? The Food and Drug Administration is looking at the safety for humans eating it and also for animals eating it, and then the EPA is looking especially at cidal activities, what's called plant incorporated protectants, and these are things that could have a big impact on the environment. [09:25] Speaker 2: Nate said cidal activities, and cidal activity refers to bactericidal or the killing of bacteria, often measured for antibiotic efficiency. Considering that our earth is covered in various microbiomes, the EPA wants to understand impact of how organisms interact, especially when it comes down to bacteria proliferating or dying out. Every organism has a role to play in our complex ecosystem. [09:56] Speaker: And Norfolk Plant Sciences, let me take a step back and give you the history of the company. [10:01] Speaker 3: That'd be great. [10:01] Speaker: We were founded back in 2007 by Professor Kathy Martin at the John Innes Centre in the UK, and Professor Jonathan Jones at the Sainsbury Lab right next door, also in the UK, both in Norwich. They had been doing groundbreaking seminal research in the field of plant biology, making discoveries in two critical areas. One in nutritional fortification of food. You know, what's the quality, what's the nutrition that we get from our food? And the other side in disease resistance. How much food in a farmer's field is lost due to pests, due to pathogens that come in and destroy them? This has a huge impact in our ability to feed ourselves. It also has a huge impact in the sustainability of our farming because if we lose a lot to diseases or we have to spray a lot of pesticides to save those crops, that has a big impact. So Kathy and Jonathan had made these seminal breakthroughs, and they had technologies and knowledge that could make huge improvements to the way that we're producing our food. But in order to use these discoveries, you really needed to use biotechnology. You needed to use transgenic approaches where you're taking typically a gene from one plant and putting those genes into another plant, where these can't be crossed through sexual compatibility. But there's this beautiful nature-based solution that allows organisms and also researchers to move bits of genetic material between organisms. And they had a lot of specific examples of great qualities that you could bring to crops using biotechnology. So they started Norfolk Plant Sciences in 2007 to try to take their knowledge, their discoveries outside of universities, outside of the ivory tower, and bring it into the real world and allow it to impact people's lives for the better. And so what's amazing, we started off this conversation on the regulatory path. 2007, they got started with the company [11:47] Speaker 3: That's amazing. That's a long path. So you guys are gonna be marketing a purple tomato, and I seem to remember that one of the first genetically modified products was a tomato, the Flavr Savr tomato. But what I seem to remember about Flavr Savr was that, and this was developed, what, in the'80s sometime? It was developed for flavor and also for making it easier to ship the tomatoes, and I don't think that product ever took off. I feel like in a way it held the industry back because of its lack of success. Is that true, or is my memory serving me incorrectly? [12:17] Speaker: So Carl, everything you say is true, and I'm gonna jump to one of the questions you had proposed, which is a biotechnology company that I admire. And Calgene, who developed the Flavr Save to- Savr tomato, they're at the top. They created so much of the knowledge and technology that we use today now for bioengineering, not just in plants, but in all organisms. They really pioneered how do you do it, how do you do it well, how do you find targets, how do you find genes that you want to modify? How do you find traits that you wanna add? How do you introduce those into crops? How do you select them? They created so much of that, and they were really pioneers. So in the business world, we often talk about, well, what is their first mover advantage, or actually is it a dis- advantage to go first, and you're better off to go second, third, learn from the mistakes, and learn from the challenges that other companies face. And that's what I see about the Flavr Savr tomato. We've learned a lot. We've studied a lot, that product and that process and also that era, and we have a new product in a new time that is meeting different unmet needs, but it's really following on the tradition that Calgene and the Flavr Savr tomato got started. [13:19] Speaker 3: Yeah, I mean, I think for listeners who don't know that, Calgene and Flavr Savr, that all took place, again, I think in the late'80s. My timing might be wrong. [13:27] Speaker: Started in the late'80s and the early'90s. Yep. [13:29] Speaker 3: It was basically a generation ago, and genetic modification of plants was still very much something that was very scary. I think people are much more open to it now. I'm talking to you July of 2023. We've had some of the hottest days on record. It's clear that we've got a climate crisis happening, but why do you think we need genetically enhanced produce, and how it might be better than produce that you find in the grocery store? [13:51] Speaker: Yeah, that's a great question. So I do believe that we need to continuously improve the plants that we're growing, the way that we're feeding ourselves. And I think the climate crisis that we're experiencing today, which is top of mind for so many people and is so absolutely urgent, this is something that's different from the'90s when the Flavr Savr tomato was coming out. And let me give a quote, which I heard first from Howard Shapiro, who's a heavyweight in the ag world. We should really make sure that we're solving the problems of today, not solving the problems of yesterday, of 10 years ago, of 100 years ago. And I think what we look at today is climate, nutrition, food security. These are such absolutely huge challenges for our society. In the'90s, these were not such a big concern that people were looking at. People were concerned about pesticides. People were really concerned of where their food came from, and you're talking about the concerns about genetic modifications that a lot of consumers have. Let me cut to the end and say consumers see things very differently today. Consumers are very open to products like ours. They're very open to technologies as long as they understand a little bit how they're made, why they're made, what problems they solve. The problem is that those of us, even in the biotechnology industry, still think that consumers haven't changed their minds in 20 years. [15:02] Speaker 3: That's true. [15:02] Speaker: And the reason is we haven't been asking the right questions. If we ask the right questions, then we see consumers are very open to this. That's what we've started doing as part of Norfolk, and it's extremely refreshing. Let me just throw this piece in. So I've been working in the area of plant biotechnology for over 20 years, and this notion that, "Oh, consumers don't want GMOs," this really is tied to the'90s and early 2000s. And not only was there a crisis about pesticides then. There was a crisis of mad cow. There was a crisis of confidence, I would say, in regulatory bodies, especially over in Europe. There were these stories of the government saying, "Don't worry about mad cow. Everything is fine. You know, it's not a concern." And then all of a sudden, oh, it was a concern. And so I think there was a lot of consumers who had real reasonable reasons to have skepticism about the food that they're eating and the safety messages that they were given. And one of the key pieces as I think about what we're introducing, biotechnology got into our food- system through plants, through animal feed. It really happened without the average consumer knowing it, without the average consumer having an opportunity to opt in or opt out. It was simply introduced in the food system, and they found out about it years afterwards. And I think those of us who are at the innovation front, we think about early adopters, we think about laggards, and it's really important to walk up that technology curve with people's knowledge. The first out of biotechnology skipped some of those steps, and now we have the opportunity to really bring everyone along on our journey, and that's been very productive. [16:26] Speaker 3: I think that you bring up a lot of interesting points, but one I'll point out is the way people start companies now is very different than they would've started even in the'90s, which is 30 years ago. And the way that company formation is taught now is solve a problem, go out and get your first customers, understand what your customers want. So I'd love to hear from your point of view, what kind of things did you guys do to get those early adopters on board? Especially since, you know, I mentioned at the beginning the USDA just proved this cultivated chicken, and for me it was really revealing to go on a place like LinkedIn and just see all the trolls or all the negative comments just saying, "Lab grown is terrible. I'll never eat this," and completely missing the point of the innovation. And I know that the cultivated meat space is very different, and it's kind of at that crossing the chasm point right now. It's like the progress has been made, funding dried up for a while. Funding was very difficult, yet people continued to make progress, and now we're starting to see the beginning of precision fermentation in the meat space. So there has been a lot of work getting the consumers ready for that. What kind of work did you guys do to get the consumers ready for this purple tomato? [17:32] Speaker: That's a great question and a great framing, Carl. What's interesting is we've been around longer than cultivated meat. And you mentioned the Flavr Savr tomato from the'90s, and there's other examples, whether it's golden rice, whether it's rainbow papaya, whether it is the Arctic apple. Consumers have known that there's GMO foods around, and even though most people don't necessarily seek it out and they have some concerns, there's at least a high level of awareness. And maybe in some sense, any publicity is good publicity at the end of the day. Because I think what we found was consumers know the term GMO, they understand biotechnology, they're interested in it, and it has a bit of a taboo quality. So our path for early adopters really started in 2008 when Cathie Martin published the first paper on the purple tomato. There immediately there were articles in The Guardian. There was a lot of interest because it was, "Okay, there's this new GMO crop that may come out. This is very controversial." And if it bleeds, it leads. So what we found starting two years ago when we began our regulatory process with the USDA is there was even more and more interest. So many of your listeners may know our product was featured on the front page of the New York Times Sunday magazine just exactly two years ago, and the title was Learning to Love GMOs. When consumers look at the pros and cons, the benefits of biotechnology, what it can do to solve the problems that we have top of mind that we touched on. And one of the things we did was we were very loud and we were very proud about our approach. We don't- apologize for using biotechnology. What we try to do, and for your listeners, I have a PhD in plant molecular biology. I've done a lot of research, but I've also tried to do a lot of communication to people outside of science. What I have found is when you talk to peo [20:45] Speaker 3: So we don't usually post the videos, but I do have a huge smile on my face. I've been lucky enough to try the tomato twice. I tried it at Ginkgo's Ferment, was impressed by it. But I think the place where it really hit me was at Synbio Beta because you guys had created vats of salsa that were top-notch. In fact, some of my colleagues from Mexico, one colleague in particular, Danielle, was so impressed, not only by the tomato but by the quality of the salsa. So whoever your salsa chef was did a tremendous job. And Danielle actually runs taco tours in Mexico City, so he's a hardcore taco foodie, and I think that compliment to your purple tomato-containing salsa is about as good as it gets. I love hearing that the reception, people wanna see it. Of course, we do. They wanna try it. It's tasty as hell. I can't recommend it highly enough. And you're right, genetically modified products are all around us. When I indulge in a bag of Fritos or Doritos, it says it right on the label, "Made with genetically modified products," and people are consuming those. As an aside, like, we're working on another product, cosmetic product where we're working, educate the public on the label because the label has to contain the name of the peptide, and the peptide includes what organism it's manufactured in. So it could be manufactured eating E. coli or yeast, but the cosmetic industry wants you to label things in a way so that consumers understand, hey, this was made in yeast. Hey, it's a fusion protein. Hey, maybe it contains a fragment from a protein that comes from a cricket or something, just so that you have that understanding. And the concern is always gonna be that there's gonna be a backlash against it. So it's super interesting to hear how this came together, and I was wondering, could you maybe explain? You said there are pathways it turned on. There's part of [22:23] Speaker: So let me pick up two strands there. So I'll get to your technical question next, but I want to touch on your point about the labeling rule, and also weave in your point earlier about the comments that you see in discussion threads,'cause I think that's really critical. The labeling rule went into effect, and it's something that a lot of the industry was really fighting against. They said, "You know, if there's a label, people are gonna see it as a warning sign, but there's no reason to have a warning sign, right? We shouldn't have a label." What we're seeing now that the labeling rule has went into effect, and it just went into effect last year, is people really don't care. They like to know that it's there. It's nice to see. For those people who really wanna avoid genetically modified ingredients, you can get organic, you can get non-GMO project verified. And for everyone else, they see it and they think, "Okay, fine." And I've talked to a lot of people in the produce industry who have dealt with those questions. And so I think one of the biggest things in this industry when we talk about food is what's the backlash gonna be? The backlash is really concerning, so you have biotech companies who are making these products, but they need to break into the market, and they need to convince the channels that this is a product worth supporting, worth carrying. And of course, there's heavy, heavy competition for shelf space for all products, non-biotech, biotech, whatever that is. To get in front of the consumer is a huge challenge in and of itself. And it makes a lot of sense that a lot of folks, especially in the retail industry, they're conservative. They don't wanna take a risk. They've got lots of products to choose from, so why do something that may have backlash? And especially if they look at the comment threads on Twitter or any kind of article, yo [26:18] Speaker 3: Hey, Grow Everything listeners. Let me explain what Nate was talking about. Cells have lots of processes going on simultaneously all the time. Cells digest food. Cells eliminate waste. They are reacting to the environment. They're turning DNA into RNA, which makes proteins. All of these things happen through different pathways, and those pathways are turned on and off based on what's happening in the cell and what's happening in the environment around the cell. The purple color in the purple tomato comes from one of those pathways. Usually, it is turned off. Nate and his team turned it on using transcription factors. Transcription factors are proteins that control how fast DNA makes RNA. They do this by binding to specific DNA sequences. So basically, Nate and his team engineered a pathway that makes the tomato purple. It's a pretty neat trick. It's pretty elegant, and let me know if you have any questions about this. [27:26] Speaker: So conventionally bred purple tomatoes, this is done through wild introgressions. It means that you have a tomato that has a lot of weird DNA that hasn't been domesticated, so it doesn't bring in good qualities for eating, it doesn't bring in good qualities for farming, but it does bring in the purple. That purple needs to be activated by light, and this is a challenge for a lot of growing environments, and a lot of your listeners will have seen when you get a purple skin tomato at the store, the top is purple, but the bottom is red. And then when you cut it in half, what you see on the inside is, it's red. Kathy's big discovery was transcription factors that activate this pathway, not in response to UV light, but in response to development. So she took a process that was environmentally regulated and turned it into developmentally regulated during fruit ripening. So in our purple tomato plants, when the fruit first starts to form on the vine, it comes out, it's green, and when you grow tomatoes, typically they're green, and then they start to turn orange. That's called breaker stage, and then they turn red. Our tomatoes are programmed genetically through development to turn purple instead. And so the transcription factors that come from snapdragon that activate the pathway, those transcription factors are turned on by a tomato promoter, which is active during fruit ripening. So it's really a beautiful, elegant system of bioengineering. It's fairly simple by synthetic biology standard, but it's a beautiful example, and it works extremely well. [28:41] Speaker 3: So then how do you know when they're ripe? If it goes from green to purple, how do you know that it's ready to pick? [28:46] Speaker: That's a great question. We had to dial this in. This was a big part of our process as we go from, okay, this is a, this is a science experiment, and there's been a lot of testing done on the biochemistry, on the health effects in a rodent model. But if you're making a commercial product that needs to go through the supply chain, then we need to really dial that in. So the answer is, it's a little bit later in ripening than you would think for a red tomato. So the purple color comes on slightly earlier than red, and the ripening is also slowed ever so slightly. So what we have learned, and we had to do a lot of trialing in our own hands to dial this in, is you look at the truss. So for those of you who have seen how tomatoes form and, you know, you go to the grocery store, you get tomato on the vine. Sometimes you get cherry tomatoes on the vine, where there's about a dozen tomatoes on a stem. Typically, the oldest tomatoes will ripen first, and the younger tomatoes will still be green. So we can look at a truss, and it's almost a snapshot in time, where you see the young tomatoes at the front and the old tomatoes at the back. So you'll see green tomatoes. These aren't ripe. You'll see the first purple tomatoes. When you feel them, they're quite firm. Those are not ripe yet. And then you build that intuition really quickly of how many to count. Okay, here's the ripe purple tomato. They're soft. We do this mostly by tasting. You can taste how the brix accumulates. You can taste how the fruit gets soft. It loses that vegetable, that vegetal flavor, and gets just that beautiful umami mix of subtle sweetness with a little bit of acid, but just that full-on summery tomato flavor. [30:04] Speaker 3: Yeah, I mean, honestly, I don't think there's anything like a fresh tomato, and if I go to a farmers market and someone is selling heirloom tomatoes, I will always buy them just because the flavors are tremendous, and they do have, like you say, that great umami taste. But I think that there's this earthiness that you get. So I grew up in California. I live in New York now. My dad always has tomatoes in the backyard, but there is this earthiness to the fresh tomato that you don't normally get when you get a store-bought one. And I think it's, uh, super interesting to hear that tomatoes also naturally produce purple, and that you guys just turned on, changed some pathways slightly to make these tomatoes purple. I think it's fascinating. There are... Th- It almost is like there is a rainbow of tomatoes that we usually don't have access to. There's so many species. And by the way, I've done deep dives on tomatoes. It is my favorite vegetable. [30:49] Speaker: Well, it's certainly my favorite vegetable, too, and one of the things that I think is really important to mention in what you just said, we love heirloom tomatoes. Different people have different definitions of what is an heirloom tomato and what's not an heirloom tomato. Right. I think we'd all agree they've got to taste amazing, and you ought to be able to save the seed and replant it and get back the same tomato that its parent was. But taking a step back, if you think as a biologist, biodiversity is absolutely critical to give us whatever it is, you know, whether it's an heirloom tomato that you really love growing and eating, or whether it's a new drug that's produced in a strain of yeast. As biologists, as people working in synthetic biology, we're constantly l- looking for that right mix of biodiversity to get us a certain trait, to get us a certain attribute. And when you look at the biodiversity that's out in nature, it's extremely grand. Yeah. It's huge. It's the product of millions and millions of years of evolution shaped by certain forces, but it is not the end-all be-all. There's constantly new biodiversity being created in the world around us, and of course, there's biodiversity being lost in the world around us. The loss of biodiversity is a huge concern, but I think I often get the question, not from you, but I often get the question from people, "Well, GMOs, aren't those a threat to biodiversity? Aren't we gonna lose biodiversity because of biotechnology?" And I understand where those concerns come from, and I do think it's important that we understand the nuances of different crops and the impacts that we're having on the environment. But I think at the end of the day, it really is increasing biodiversity, and I love your view of you have a rainbow of tomatoes. We often say eat the rainbow, and of course, we have a rainbow of produ [32:48] Speaker 3: Yeah, I love it, too. I mean, I'll just mention, I don't think I've ever been to a farmers market where people have a lot of different kinds of tomatoes. The thing that really blew me away many years ago was I went to Avocado Fest in Carpinteria, California, and I grew up around avocados. I grew up in Ventura. Half of Ventura is lemons, the other half is avocados, and there is a lot of tomatoes grown there. But turns out that UC Irvine has the largest library of avocados in the world, and so at Avocado Fest, people from UC Irvine had brought this huge diversity. There was probably 80 or 90 different kinds of avocados, most you never see, and market forces basically have dictated that the two most popular tomatoes that we get... or two most popular avocados that we get are Haas, and then like another one that I don't know, I never remember the name of because I don't really like them as much. But- Yeah there's tomatoes that are the size of a walnut, there are tomatoes that are the size of almost like a small watermelon. They're all completely different. They have different flavors. I walked away with a couple of really big ones to bring back to my kids. But on tomatoes, it's even... the biodiversity is even greater than it is with avocados. But then this begs the question, are tomatoes vegetables or are they fruit? [33:53] Speaker: Oh, I love that. Well, let me answer the last one first, and then I'll dive down your rabbit hole,'cause that's what I love. Legally, according to taxation and nutrition, in the US, they're a vegetable. Botanically, they're a fruit. [34:04] Speaker 3: Interesting. [34:05] Speaker: Easy. I think what you bring up, though, is so key, your point about market forces. We talk about biodiversity, we talk about the, the flavor of heirloom tomatoes. You talk about 80 to 90 diverse varieties of avocados and how great they taste. You talk about bananas. Almost all of our bananas, a single variety, the Cavendish, it's susceptible to this devastating disease, and yet you can travel to parts of the world, like in India, where there's tons of different types of bananas, and they taste so good, right? And you think, "How could it be that we only have this one variety here?" And I think there's two answers to this, which you've said already. There's the question of biodiversity and what are some better varieties, and that's really where Norfolk Plant Sciences got started, right? Let's make a new variety of tomato that's better and different in certain ways. But the market forces are so absolutely critical, because those are setting the criteria of what crops can get out to market and what can't. And it's been interesting to see, especially in the fresh produce industry, how that's evolved over the last few decades. I'm in the camp of it is a miracle. It's the product of thousands of people working very hard, doing excellent work at their job, solving a problem, which is the vast majority of people, speaking for the US, for North America, they want to go to the grocery store any day of the week, and they want to be able to buy most of the fresh fruits and vegetables that they regularly eat, and they may not want to think about what month of the year it is or what's in season- Right or where things came from. I'm not necessarily that way. I really like seasonal, I like local. Most people do. But I think the market forces that have shaped what's available to us now are meeting the needs of the average consumer and what's needed. I constantly thin [37:43] Speaker 3: Well, it is my favorite to eat when it comes locally, but it's not my favorite when I buy it at the grocery store. How's that for the answer? Yeah. But I think just talking about supply chain and supply chain resilience, I think most, most of us, like you said, just take for granted produce that we have in the grocery stores. You never think about it, and unless you look at the label, you don't realize, hey, the bananas are coming from Panama and Costa Rica, these grapes are coming from Chile, these avocados are coming from Mexico and the Dominican Republic. It is a very robust global supply chain, and I think that it's also very fragile. And so given what we're gonna see over the coming decades with climate, I could see the supply chains being disrupted in a way that doesn't necessarily have to be negative. It could be a very positive thing. And, and it doesn't mean that you won't be able to get your purple tomatoes, and I want to talk about how you guys grow them, and well, it doesn't mean that you won't get them in the dead of winter in Vermont, it just means that they won't be shipping, you know, from Chile. They might just be being grown in Virginia or in a greenhouse in southern Vermont. [38:38] Speaker: 100% agree. So, so two pieces that I want to touch on with this. Let's start with the first piece, which is when climate change, as it gets worse, as we have more shifts in, okay, we've always grown tomatoes in these areas, now the weather is not conducive to that anymore, so these areas need to grow something different and then we've got to grow tomatoes in another region. Farmers and growers are constantly adapting their mixes of what they produce, and this is just going to accelerate. One of the things we know is that if you move producing crops from one region to another, you almost always have to adapt new varieties. The day length is different, the temperature, the humidity, precipitation, all the factors are different, and you really need to have varieties that are adapted to those regions. One of the things that we think about is do you adapt based on evolutionary timeframe? That can be very slow. How can you accelerate that? So you can add mutations, you can do speed breeding, um, but- By adding in biotechnology traits, and this is an area where CRISPR and gene editing can come to play in a big way, but also adding transgenic traits. This can help in a huge way to adapt crops to new areas, to adapt to climate change. And I think the speed of adaptation is going to become more and more important in decades to come as climate change accelerates. The other thing that most of us don't think about, but I think once we talk about it, it's obvious, is plant diseases are extremely important. So think at one point we had no COVID-19, then we had COVID-19 all of a sudden. This is, this is the most important thing. This happens in plants all of the time. So in tomatoes, in greenhouse production, it's a new virus called brown rugose virus. This has upended the industry because In most areas that are growing a lot of tomatoes, if you have susceptible plan [44:35] Speaker 3: Yeah, I'm fascinated by this... What did you say? CEA, is that what it's called? [44:39] Speaker: CEA, controlled environment agriculture. [44:42] Speaker 3: Yeah, because I've seen that, and I'm under the impression that this is the case, at least on the East Coast, much of the lettuce, especially, like, the organic lettuce, organic spinach that comes in these plastic containers that you can see, and we buy it all the time, I think most of that comes from these controlled environments,'cause I saw a guy who is a founder of one of these companies, and I think they're based in Kentucky, though there are some local ones here in New York City. But this thing about doing more localized production of food, making it more sustainable so you cut the miles out, this is something I'm super interested in, and we've been doing a little bit of a deep dive on the cultured meat side because we're curious, okay, what size bioreactor do you need to feed a city of 100,000 people, a million people? What does that look like? Those kinds of questions are on my mind. How do you make a city more resilient? How do you localize more of the food production? And the freight company that you mentioned is fascinating to me because that basically means you can set these things up so that if we want a certain number of purple tomatoes in Vermont, we just get a couple of these containers in there while we build our facility or something like that. [45:36] Speaker: Well, and, and you're absolutely right on, Carl, and that's been done already by many companies. And Freight Farms has a lot of farms at institutions with grower packer shippers even who are building out greenhouse facilities, and they want something immediately. I think we're in a really interesting place, and the same goes for precision fermentation. What is it gonna take to service a metro area and- Can we have a distributed hub-and-spoke model that is really favorable? Right. You know, you do the life cycle analysis, you're looking at all your emissions, scope one through three, and you can say, "Look, we've looked at the metrics, we've looked at the data. This is better for the climate. This is more sustainable." I think that's where we all wanna get, and I think our industry, let's say synthetic biology and everything it touches, is in the messy middle. Right. We are in the challenge of scaling. We are in the challenge of unit economics. We are in the challenge of consumer adoption. And in many places, so the controlled environment agriculture industry is in the middle of this right now. I think a lot of syn bio is, where we've been making promises for a long time. There's been some early successes, but a lot of us are still waiting to see the big breakthrough companies. So if you think Genentech with insulin- Yeah I think you can look at Impossible Burger maybe as the next one, that they, they really did it well. They did a, a huge splash, and they sort of set the tone, okay, this is a real new category of products. These are gonna be strong, these are gonna be growing. And now we're looking at, okay, controlled environment ag, how are the costs gonna come down? How is the business model really gonna work? What are the products that are gonna come out? How is the consumer gonna realize that these are different? So you recognize, okay, it seems [47:53] Speaker 3: Totally. Now, you mentioned that you guys are developing other products. Could you give us a hint as to what those are? [47:58] Speaker: Absolutely. So the product that we have regulatory approval for is the purple tomato. You've had the purple cherry tomato, the snacker, and you had the salsa. These are the first two products that we're gonna be testing on the market, so in a few small areas, these are already available. We're moving towards test markets in 2024, and then building out that product category with a bunch of different varieties of purple tomatoes. So we want the heirloom slicer. We want to make a purple tomato juice. There's a lot of other products that we can do based on this technology where we already have the regulatory path. [48:28] Speaker 3: Awesome. [48:29] Speaker: Cathy Martin and Jonathan Jones, our founders, I mentioned earlier, they have a lot of innovations that they've developed through their basic research, and this touches on disease resistance, and this touches on other nutritional fortification, whether that's resveratrol, the healthy component that's in red wine, or vitamin D, which can be brought in with a gene edit trait, not even a transgenic trait. There's many other distinctive added nutrition traits that we can bring into tomatoes, and- So that's very much in our future. And then we're already looking at other crops. So of course, we don't wanna stop with tomato. There's a lot of other crops that have room for improvement, and so we're looking at the other crops that are grown together with tomato. That's cucumber, that's bell pepper. We're looking at some fruits, so we're looking at strawberry. There's a few other areas that we're just starting to get into. And one of the critical pieces for us, we've gotta have a biological path where we can make something better. We need to have a product that's gonna fit into the supply chain, as we discussed. But what's most important for us is the consumer. Their experience, is it something that they really want, something that they really need, something that fits into their life and makes it better? We really want to focus on those innovations that are gonna make a splash with people, and have people say, "Oh, what is that? You know, I had dinner at Carl's house last night, and he had this crazy dish with a purple tomato. I think he got it at Shooks down the road. That's where we're gonna go shop. We're gonna pick this up." And we're really excited to do this, not just based on what can we do as biologists, but how can we mix the biological possibilities, the supply chain constraints, to meet that consumer unmet need? [49:57] Speaker 3: Yeah, I'm so excited. We had Eben Bayer of Ecovative on a couple episodes ago, and Eben talked about MyForest Foods. I live in Brooklyn, and we've got two supermarkets, like a block away, and I was at one of the supermarkets and I saw that they had, on the shelf it said MyForest Food, and I was like, "Where is it?" And the guy's like, "Oh, it's not here yet." And I was like, "Why are you guys advertising it?" And then it was there a couple days later, so I bought some. But then I went to a coffee shop near my office, which is a few neighborhoods away from where I live, and the coffee shop was also advertising MyForest Foods. So I took a picture, put it on social. I'm very excited to see that, and that is a non-genetically modified, you know, mycelium product. But I'm super excited to see your product show up on the shelves, and to share it and to use it in the way that you exactly said. Now, I'm curious, do you think... Okay, so we've got several organizations that are out there that cert- or that are independent organic certifiers. Do you think we need an independent pro GMO certifier? [50:50] Speaker: So Carl, I'm so happy you asked that question. I think we don't need an independent pro-GMO certifier because in the US, the USDA is doing it for us, as they have done with organic as well. Let me dive into that rabbit hole, but give a quick disclaimer at the front. And as you mentioned, Edmund Bayer, who I'm a huge fan of, and I think My Forest Food, and I don't care that it's not GMO. Right. I'm not one to say everything should be GMO. It is certainly not the case. It's not a silver bullet. What I think is, we should be trying to make the world around us better all the time, and we should use the tools that we have available that are safe, that get the job done that we need. And there's so many tools in our toolbox if we think as being biologists, as we are people who are making food, who are solving problems. And, you know, biotechnology, and especially transgenic technology, is just one of those. We can do a lot without that. We can do a lot with it. Now, your point about do we need an agency or a, a certification for pro-GM, Carl, I'm on the industry advisory group for the USDA's Agriculture Marketing Service. So we had a meeting all together with this group, and it's really a fascinating, diverse group. You have a couple people who are in a little bit the, the biotechnology space. You have a lot of people who are in the traditional fruit and veg supply chain. You have people who are running food hubs, local distribution centers to connect local growers with local consumers. It's really a huge diversity of perspectives of areas of the industry. And we had a lot of presentations on the USDA's organic program, and they have a really big focus on enforcement. How can we make sure that something that carries the organic label is really organic? 100% of the ingredients went through there. That's their big focus. We then had presentations from the peop [52:27] Speaker 3: Yes, I [52:27] Speaker: have. It's... Yeah. So it looks very similar to the USDA organic. USDA put this out. They said, "Here's how we're doing to make sure that anything that is bioengineered has this label. So we're gonna make sure if it's bioengineered, it has to carry the label." The organic is the opposite. We're gonna make sure if it has the label, it really is organic. So I raised my hand and asked the question, "So if something has a bioengineered label- But I think maybe it's not bioengineered. What do I do about that? How do we make sure that it really is bioengineered to carry the label? And the people laughed, and they said, "Why would anyone wanna do that?" There was, there was a belief even from the USDA that bioengineering is a warning label. Organic is not a warning label. Organic is a premium label. Bioengineering is seen as a warning label. So my belief, and this is, this is one of my big, hairy, audacious goals, is five years from now, and I don't think it's even gonna take that long, the bioengineering label is gonna be a premium signal akin to the organic label, and we're gonna see this plastered on products, and people are gonna be picking it out, and they're gonna say, "Hey, I love this product. It's better through bioengineering." It's not because it was bioengineered, but the thing that I love about this product, it has extra antioxidants- Right it looks beautiful, it tastes great, was enabled by bioengineering. [53:32] Speaker 3: Yeah, I'm with you. I want that to be the big goal. And it's super interesting to me because it's like doing work in the beauty space, but one of the areas of growth is green beauty. And then you see people talking about natural beauty, and then you get into this whole thing about, well, natural, and we've done this in bio space, where natural doesn't mean what people think it is. People think natural means, "Oh, it comes from a plant." But then they don't realize you can have something that's natural but that is produced in E. coli or yeast, and it's the same ingredient. But then people will say, "Oh, but that's synthetic." Well, no, it's actually the same. So you start to get into these arguments about what is natural, and so I find this idea of putting that bioengineered label on something as the premium, I think people are gonna start to realize that there's so many benefits to things being bioengineered, like all these things you're talking about, nutrition, about sustainability, about durability, about shipability- Yeah local, local production. All those things are embodied in that bioengineered label. [54:23] Speaker: I love that point, and people might think, "Oh, bioengineered is not natural. It's the opposite of natural." And this word natural is quite a weasel word. It is. Um, I wanna give a shout-out to Jonathan Jones, one of our founders, who I think I might have first heard him mentioning this on a recording of the Ali G Show about 20 years ago- where he talks about, you know, this natural thing is such a weasel word, and if you get sick with an infection, the natural thing is not to take antibiotics. The natural thing is to die. There's a lot of things that are unnatural in our society and our lives that we take for granted, and I, for one, am pretty grateful for. [54:54] Speaker 3: Yeah, natural can also mean deadly. Plants produce many poisons to protect themselves. [54:58] Speaker: Yeah, and it's important for us to have that context. Again, I think a lot of consumers are very astute now. If you think in the'90s, when this natural phrase came into fashion, it was counter-positioning against this deep industrial, synthetic, artificial, maybe picture the cheapest TV dinner or something. And that counter-positioning really worked, but now it's sort of run its course. This is my perspective. Now there's an opportunity to say all those things that you like about natural, we can do that, but we can add bioengineering on top. There's a professor at UC Davis, Pam Ronald, who's in plant biotechnology. She wrote a book called Tomorrow's Table, which outlines a case of taking organic farming methods, combining them with biotechnology methods, and coming up with a food system that takes the best of all of these worlds. And that, frankly, is my vision for the future. I think dogma is not very helpful for us. I think science, I think data, I think critical- Thinking and creativity is really what's gonna bring us forward. Whether it's new ways of producing our food through agriculture, whether it's precision fermentation for food, for beauty products, I really think it's important that we look carefully at the dogma that we're adopting, we look carefully at what are the resources, what are new ways that we can reframe the problem, what are new ways that haven't been tried, and how can we pull these together and weave them together in a way that does it better. And I, for one, am encouraged if we can get beyond these notions of natural, of organic. The term of art now is regenerative, which is still being defined, and I think what we agree is the objective is sustainability, the objective is health and nutrition, the objective is equity, it's accessibility, it's fairness, and are we really doing the best that we can to get to those objectives? [57:21] Speaker 3: Yeah, I agree. I wanna be very mindful of time, Nate. Is there anything that I didn't ask that you think we should've covered? This has been such a fantastic conversation, I have to say. [57:30] Speaker: Nothing pops to mind, Carl. I know, uh, we'll, we'll have to do this another time'cause there's- Yes so many rabbit holes we could've gone down that we didn't. But I'm really encouraged by the response that I've seen from so many communities, from the synthetic biology community, from the ag community, and I think that's more and more important for us to be telling our story, but also showing what it connects to and representing the larger context. So I really appreciate your invitation to speak to you today, and I look forward to more. [57:55] Speaker 3: Yeah, I'm looking forward to it. We'll have you on as a regular. I wanna hear more about your progress. Everybody should be looking for the Norfolk healthy produce purple tomatoes in their grocery stores as they become available. I highly recommend them. Nate, thank you so much. We'll talk again soon. [58:08] Speaker: Thank you so much, Carl. Appreciate it. Have a great one. [58:10] Speaker 3: You too. All right, so Ira, what do you think of that interview? [58:18] Speaker 2: I'm so blown away about this. I mean, there's so many topics that were covered. I really wish that I was there to talk to him, but you covered it perfectly. Like, you and I have a hive mind. When Nate was talking, I was like, "I want to ask him this question." You came right in, asked the exact question that was in my mind, so that's perfect. [58:33] Speaker 3: Thank [58:33] Speaker 2: you. It was perfect. Yeah, thank you. I mean, like, this is what happens when you work together, I suppose. [58:37] Speaker 3: Yeah. [58:37] Speaker 2: So there are a few things. Like, first of all, let's just get to some of the things that were related to what we do on the daily, right? So I really appreciated the fact that when he was just talking about the tomato and his work, he's a CEO. He's trained on how to speak about his product, and it is a very delicate situation because there is some genetic modification happening. But the way that he said it was there was a mixing of genetic material. I don't think he mentioned breeding, but breeding and introducing this genetic material to this product I thought was a really great way to talk about this type of process. I don't even want to say technology anymore, to be honest with you, Carl, because technology is often seen as something that is cold and computers and, like, not biology. But I really appreciated the fact that at parts of this interview, Nate was positioning the tomato as a flavorful biological product. It was just great because you and I and our team here at Messaging Lab are always thinking of ways to talk about biology and biotechnology in a way that is friendly and welcoming. And even if you look in the Oxford Dictionary, it's a horrifying definition for biotechnology. It's like the manipulation and exploitation of biology, and I'm like [59:50] Speaker 3: Wow. [59:50] Speaker 2: All right, relax, Oxford Dictionary, relax, right? Like, let's just reframe this. Mixed genetic material sounds better. It is also accurate. There's a nature-based approach here. We're not thinking about silicon and changing the DNA structure into something that's silicon based versus carbon based. Like, let's relax. So I did appreciate that about Nate's commentary.

Speaker 3 [01:00:11] Yeah. I'm super excited for more products like this, and I think that towards the end of the conversation where Nate was talking about how the bioengineered label has been looked at as a warning, whereas the organic label has been looked at as a premium, and he believes the same for organic over the next few years, I think that's totally gonna be true. There is no doubt. And one of the things that I want to do is go back and read The New York Times article about them, which is a couple years old. I will make sure that we link that in the show notes. We started the conversation talking about Flavr Savr, one of the very early genetically modified products. That was in the'80s. It's 40 years ago. Things have progressed so much faster. And, you know, at the beginning of our commentary, we talked about the heat and the climate, and I always joke around, and I always say it, and I'm totally serious, we need every solution everywhere all at once, and I see the stuff that Nathan and his team are doing is just a part of that solution. There's a lot of other solutions that we need. I think it's also just worth reminding the audience that there is a difference between transgenic and gene edited. The difference is that transgenic means that the organism, could be a plant, could be an animal, has some new genetic material inserted into it from an unrelated organism. So that's something that when people used to think about GMOs, that's really what they were talking about, was a creator of transgenic organisms. I don't think that the fear of that is as overblown as it was 30 or 40 years ago.

Speaker 2 [01:01:34] I remember back in the'80s or'90s that there was propaganda where there was a fish on a tomato to de- To like comment on the Flavr Savr, and that was like a fish being mutated or like being implanted into the tomato, right? This is how bizarre people were thinking about it.

Speaker 3 [01:01:51] I don't remember exactly. We'd have to look it up, but I think that there was a gene that prevents them from freezing, which was inserted into the tomato. But again, I'm, I might be totally wrong. So the other thing that Nate talks about is gene editing. So we talked about transgenic, and gene edited means what you're doing is you're taking the existing pathways that are in the, the organism, and you maybe you're turning things on or off. Biology's pretty complicated. There's a lot of, depending on the developmental stage of an organism, genes are turned on and off naturally. But using new gene editing technologies, you can manipulate when certain genes are turned on and off. And that's really important because, like, for example, for these guys, as Nate mentioned, there are purple tomatoes or partly purple tomatoes. So if they turn off or turn on a pathway, they can make the tomato completely purple. We'll have to look into a little bit more detail and we'll include that in the notes. As we sign out or get ready to say goodbye to this episode of the pod, I think there's a couple things we should just mention. We wanna give a shout-out to our friend Michael Kopke at Lands Attack. He is changing his role, and so congratulations, Michael. We're super psyched for you. We can't wait to see you again soon.

Speaker 2 [01:02:56] Yeah. And then we have a, a lot of friends that are entrepreneurs, they're founders of companies in our space of biotech, and they recently closed rounds of funding. We should check in with our friends to make sure that we can announce it, but once we check in with them, we'll let you know who they are. Great feat. It's one of the most challenging things about being an entrepreneur is raising venture capital. So you know who you are. Congratulations to you. We will see you soon, and we'll talk about announcing your successful closing of a round.

Speaker 3 [01:03:22] Okay. And then you put this note in our notes, Erum, where you say, "We need a hotline so people can call and text us." I don't know what you're talking about.

Speaker 2 [01:03:29] Yeah. Well, I think we do. So for example, let's say one of our friends, Alex Rose, for example, like he's listening and wants to chime in on something. Why can't someone just like text us? And I know right now can check your Spotify, if you're listening on Spotify, there's a question there where you can answer that, but that's a little bit more one way. But if someone had something on their mind while listening, let them like text us. I know that our friends at The Pivot podcast, they're not our actual friends, but we love Paris Buscher and Scott Galloway. They have a, a phone number. So that's all that I was thinking about is maybe we could be like, "Hey, any thoughts or ideas? Text us at 444-444."

Speaker 3 [01:04:02] Right. Right. I also wanted to say thank you. I don't have the name of the last person who reached out and told us how great our podcast is, but there have been a few people who've been reaching out via LinkedIn or emailing me directly. So I just wanna say thank you. Next time we record, I'll make sure I just give you guys a shout-out because we do appreciate, uh, all the compliments, all the comments, all the suggestions. We've got a bunch of great episodes in front of us. Unless there's anything else, Erum, I think that's the pod.

Speaker 2 [01:04:31] Yes, that is. We will see you next week.

Speaker 3 [01:04:33] Awesome.