Can tomatoes made using CRISPR help relieve stress? In this episode, we take you to Japan to learn more about the first CRISPR food available on the market. We also take you back to the 1990s to speak with scientist Dr. Belinda Martineau, who helped create the first GMO whole food, which was also a tomato.
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Credits
A CRISPR Bite is supported by the Jean Monnet Network, which is funded by the Erasmus+ Programme of the European Union through the GEAP-3 Network of scientists. More about our project here. This podcast does not reflect the views of our funders.
This podcast was co-written and hosted by Dr. Lauren Crossland-Marr. Our executive producer is Corinne Ruff. She co-wrote, edited and produced the show. Jake Harper edited this episode. The show was sound designed and engineered by Adriene Lilly. Aaron Crossland made our theme music. Rachael Marr designed our logo. Legal support from New Media Rights.
Thank you to the GEAP-3 team! Special thanks to Matthew Schnurr, Klara Fischer, and Glenn Stone for their support and advice on this podcast. Special thanks to Fumino Tamaki for her help with organizing the Japanese interview.
Leave a 5-star rating and review of this episode on Apple podcasts to help us spread the word. Have more to say? Email us at acrisprbitepodcast@gmail.com.
Lauren Crossland-Marr: I'm a huge biotech nerd, so I got pretty excited when I heard some news out of Japan about the first CRISPR edited food to land on any market. Listen to this TV shopping style ad I found on Sanatech Seeds’ Facebook page, posted in January 2022. Sanatech is the company that created the CRISPR edited tomatoes.
新時代の健康トマト -- The video is of course in Japanese. It's promoting the company's at home tomato harvesting kits. And these tomatoes are really special, because they were designed to have increased levels of GABA, an amino acid that's been shown to decrease stress. This was the first time ever that CRISPR was used to modify a whole food.
That's a term scientists use to mean fruit in its natural, unprocessed form. That on its own was really exciting. But it also reminded me that the tomato was the first whole food to be edited using earlier, older GMO technology. So what is it about the tomato that led scientists working with two different technologies decades apart to use this fruit? Well, to put it simply, They're easier to modify, and lots of people eat them.
This is A CRISPR Bite. I'm your host, Dr. Lauren Crosland Marr, and today on the show, tomatoes. I'll take you back a few decades to talk about the history of the flavor saver tomato and GMOs, and why a scientist who worked on that project is cautioning consumers to question what's going on with CRISPR in food today. Then we'll go to Japan to learn why one company is using CRISPR gene-editing technology to add more nutrients to tomatoes, and also find out what those tomatoes taste like.
Haruka Nakata: They just smell like normal tomatoes.
Lauren Crossland-Marr: The story of gene edited tomatoes starts in the late 1980s. That's when a handful of scientists working for a company called Calgene began to create the first GMO whole food. They called it the Flavr Savr Tomato. Dr. Belinda Martineau was one of the genetic engineers who set out to create it, with the intention of editing its genes so it would stay fresh for longer.
Belinda Martineau: In broad terms, it was the first genetically engineered whole food to be commercialized on the planet in history. And, uh, we had a certain trait that we thought would, uh, well, we, the business folks at Calgene thought would make a good fresh market tomato product. And, uh, so that's what we did.
Lauren Crossland-Marr: I caught up with her outside of Paso Robles, California, in April 2022. She's petite with long gray hair. She has a warm, approachable personality and a great laugh, but I can also feel the grit in her voice when she talks about her old research, which she did at a time when there were far fewer women in lab coats. I really wanted to talk to her because she was a critical part of creating the first GMO whole food, but now she's a skeptic on how gene editing is being used in whole foods.
CRISPR wasn't around nearly 40 years ago when she was working on gene edited tomatoes. Back then they used an older form of genetic modification to create genetically modified organisms, or GMOs. One way scientists did this was by introducing DNA from another organism. That's what scientists call transgenic, trans from the Latin root on the other side, and genic meaning genes.
For more on the difference between GMOs and CRISPR technologies, hit pause and go back to the first episode if you haven't already heard it.
[Rewind noise]
Okay, back to Belinda. Her team set out to make grocery store tomatoes last longer. You know, farm fresh, vine ripened, sturdy enough to make it to the marketplace, um, like your homegrown in your backyard tomato. You've probably noticed a huge difference in taste between your farmer's market tomatoes and the ones you buy in the supermarket, and that's not your imagination.
The tomatoes you buy at the supermarket are picked when they're green to make the trek to the store. Since consumers want their tomatoes red, companies put them in ethylene gas chambers to redden them. This is the same gas tomatoes use to ripen naturally. However, speeding up the process only changes the color and doesn't necessarily ripen the tomato.
Creating a longer lasting tomato wasn't quite as simple as scientists at Calgene thought, and there were a few mishaps along the way, including a messy trucking experiment. At one point, the scientists were working on field trials in Mexico of a few varieties of the flavor saver tomato, and they decided to have them shipped in a truck to Chicago, Illinois, to test whether the fruits would make the trip in one piece.
Belinda Martineau: The business guys are out there meeting this truck that just came up from Mexico and they knew the answer to the experiment before they even opened the door to the back end of the truck, because tomato juice and puree was flowing out the back side and they ended up shoveling the tomatoes out of the truck.
Lauren Crossland-Marr: I love that visual. There's nothing quite like seeing a trail of red goo flow out of a truck to know your experiment didn't work. And they had a lot of things to sort out before the company could bring the tomato to market. Like, do consumers even care about extending shelf life? And could they make enough money to cover the costs?
Belinda Martineau: But shelf life isn't something that the average consumer probably cares that much about either. So the business staff really started interpreting this non rotting trait as, all right, well that will allow us to let it ripen on the vine longer. Still be firm enough because it's not rotting to make it to the marketplace in a truck. And we'll save money. The consumer will get a better tasting tomato. It's all good. But it turned out that our anti-rotting really worked after the tomato was fully ripe. And our tomatoes, for the most part, softened just as much as any other tomato while it was ripening. The rumor around Calgene was, when we were selling them for $1.99 a pound when they first came out in 1994, it was probably costing us $10 a pound to get them to market. So, the point I'm trying to make is that some of these decisions are being made because of how big the fresh market tomato market is, and for money reasons. And we had to push a product because we had gone back and asked the venture capitalist for money multiple times and we were getting to the point where we had to get a product on the market or, or that was gonna be the end of the company.
Lauren Crossland-Marr: So the product, the business folks decided had the best chance of making money was a tomato that the scientists would figure out how to genetically slow down the aging process. And scientists did finally figure it out.
Belinda Martineau: And we did it in the lab. You take a wild type tomato and your transformed tomato and set them on your lab bench. Six weeks later, the wild type is a pile of goo and your tomato looks just like it did six weeks ago.
Lauren Crossland-Marr: The tomato that worked lasted five to six weeks after being picked ripe, which was a huge success. But how did it taste?
Belinda Martineau: It did not taste any better than your backyard tomato. And in fact, we were throwing the transgenic gene into a bunch of different tomato varieties, because as it turned out, the research on, uh, good tasting tomatoes was not very well developed back then either. So the best tasting tomatoes at the time in the 90s came from a breeder in Florida who had an assistant and their method for selecting good tasting tomato varieties was to walk through their fields and taste the tomatoes. One of them liked them sweeter, and one of them liked them with more acid. And so if only one of them liked it, it got thrown out of the program. They both had to like the tomato, and that's how they selected their varieties for taking forward in their breeding program. Back in the day, uh, we were just trying it in everything. And so some tasted better than others, but, um, it wasn't consistent. And, and that's what Alice Waters told me. ,
Lauren Crossland-Marr: That's Alice Waters, the world class chef at Chez Panisse located in San Francisco.
Belinda Martineau: And she was not gonna serve them at Chez Panisse because they weren't consistent. They weren't very good tomatoes.
Lauren Crossland-Marr: It's safe to say that famous chefs might be a little pickier than the average home cook. Supermarkets were still really interested in stocking the tomatoes for customers. So, success, right? Well, not quite. Calgene's tomatoes never took off. The company went bankrupt shortly after creating the tomato.
Belinda says Calgene was a biotech company. They didn't know how to be a grocer. These were scientists doing field trials. They weren't in the produce market. For Belinda, this market failure speaks to a larger issue, mixing science with business. Belinda says executives told her to adjust her data because it didn't support the outcomes they were looking for to market the product.
And that was a huge red flag to her. I mean, you can't just change science because it doesn't make your product look good. But you also have to remember that the main objective for the business guys was to make money and keep the company going. They didn't necessarily care about making the. best tomato. And that perspective clashed with scientists like Belinda, who were excited to play around with this new technology and see what it could do. That was the fun part.
Belinda Martineau: I'll never forget the time I was asked to remove those error bars from my graph because they were confusing to the business staff. But those error bars on that particular graph showed that there was really within the margin of error, no difference between the taste of our tomatoes and the taste of the grocery store tomatoes. But if you remove those error bars, ours looked a little better. And so the business staff liked that more. So it got frustrating as a scientist to work with the business staff.
Lauren Crossland-Marr: This is what makes her skeptical about gene editing and food. Business interests and financial incentives sometimes push ahead products before they're ready for prime time. This push and pull can also be a concern for regulators like the food and drug administration. Before Calgene could go to market with a tomato. It needed government approval, and as part of that process, the FDA wanted the company to prove that there weren't any unintended gene changes.
Belinda Martineau: How, uh, noisy are my results going to look? Sure enough, 20 to 30 percent of the time, the whole darn vector beyond the tDNA borders had gone in. And, uh, that shocked me, actually. I just, it was totally unexpected. And, you know, to this day, I don't believe that issue has been rectified for GMOs. You still have to basically look. Sometimes it goes in, sometimes it doesn't go in. So you just have to screen your plants and throw the ones away that have any extra DNA in them.
Lauren Crossland-Marr: Belinda could see the change that she intended. That part was fine, but her results were unexpected because there were also parts of the transfer DNA, also called tDNA, the natural bacterium that carries the genes of interest into the plant. She found that the tDNA was in the genome up to 30 percent of the time. The issue is that it shouldn't have left anything behind at all. What worries her the most is that, she says, scientists can't predict when the tDNA will stick around. They just have to look for it. And that's what the FDA wanted. Eventually, Calgene did get FDA approval for the gene edited tomato. But that didn't change Belinda's doubts about the speed of the process.
Belinda Martineau: That was one of my epiphanies. Are we really ready to take this tomato to market when we don't, we didn't know that. It's unexpected things like that can happen.
Lauren Crossland-Marr: She thinks that's why consumers should be cautious about these new products coming out. As she experienced with the Flavr Savr tomato in the early 90s, unexpected things happen in science.
Belinda Martineau: We were working with a very new technology, it hadn't been used for any food products that had been commercialized anyway at the time. And so, being new, we didn't know all the ins and outs about it. And so that would be my warning for using new technologies. That we found out things along the way after we started this conversation with the Food and Drug Administration.
Lauren Crossland-Marr: So where does that leave us today with CRISPR and tomatoes? We have to go to Japan, at least by Zoom.
In 2021, I heard that the tomato was again the first gene-edited whole food to go to market, this time using CRISPR. The company behind the tomato, Sanatech Seeds, successfully created the first gene edited direct to consumer tomato. It seemed to me that the Japanese startup had developed seeds that, at least in part, actually achieved what Calgene was set out to do decades earlier. But instead of creating a tomato that would stay fresher for longer, Sanatech developed one with better nutrition.
The tomato, a Sicilian Rouge varietal, has an increased amount of GABA. That stands for gamma aminobutyric acid, and it's an amino acid that has been shown to lower blood pressure and stress levels. Tomatoes naturally have some GABA. However, using CRISPR, scientists shut down the existing genes that make sure there isn't too much GABA in the tomato.
In the case of the tomato edits, scientists basically remove the part that regulates the amount of GABA so that more flows through the fruit. This means the edited tomatoes have way more GABA than usual. The thing I couldn't figure out, though, was why is this something consumers wanted? Right now, the product is actually only sold in Japan.
While researching this episode, I tried many times to interview scientists and business leaders at Sanatech Seeds, but they never got back to me. So I decided to start asking around through my own connections. My best friend's cousin lives in Tokyo and offered to get a hold of these tomatoes and taste them for me.
Her name is Haruka Nakata. She goes by Haru. We recently hopped on a zoom call to buy the tomatoes. It's pretty cool. You can buy this stuff completely online and Haru shares her screen and navigates to a website almost entirely in Japanese. The only words I can make out are GABA and a few numbers. There are pictures of small cherry like tomatoes.
Haruka Nakata: It does look like normal tomato and also it looks very fresh and bright red. So it looks very tasty and pricing of them the 300 gram two packages is 15 dollars. Two kilo is 37 dollars and three kilo is 52 dollars. So yeah it's compared to a normal tomato it's expensive but it's It's not crazy expensive.
Lauren Crossland-Marr: She goes to the checkout, and I see that with shipping, our total is about $50 for just over a cup of cherry tomatoes and 15 ketchup sized packets of tomato puree. Now we just have to sit around and wait for them to arrive. A few days later, Haru sends me a text full of tomato emojis. My friends, the tomatoes are here in my house, yay! We hop on a zoom again and she holds up a small round tomato, squishing it between her two fingers. Hello Haru!
Haruka Nakata: Hello, hello, hello.
Lauren Crossland-Marr: You got the tomatoes!
Haruka Nakata: Yeah, I have a bunch of tomatoes.
Lauren Crossland-Marr: Wow, that's a lot of tomatoes. What do they smell like?
Haruka Nakata: It does smell like normal tomatoes.
Lauren Crossland-Marr: Really? They're pretty small, huh? They look like, um, strawberries.
Haruka Nakata: I know, it's like a little different from normal Japanese tomatoes. Usually, It's very round.
Lauren Crossland-Marr: Can you taste one for me? I want to know! I wish I could try one.
Haruka Nakata: It tastes good.
Lauren Crossland-Marr: Really?
Haruka Nakata: Mm hmm.
Lauren Crossland-Marr: Like a normal tomato? Mm hmm. Do you feel relaxed?
Haruka Nakata: It tastes like normal tomato and with little of sour.
Lauren Crossland-Marr: Oh, they're sour. A little more sour?
Haruka Nakata: Mm hmm. But it's not like I can't eat because it's sour or something. It's just normal tomato, but a little bit sour. But I like it.
Lauren Crossland-Marr: For pretty normal tasting tomatoes, I keep thinking about how pricey they are. It reminded me about the cost of the Flavr Savr Tomato and how much the company was losing on them. Since no one at Senatech got back to me, I have no way of knowing if the business side is working out for them, or if consumers are willing to pay these high prices.
How do you feel? Are you, are you like nervous about eating a crisper tomato?
Haruka Nakata: Uh, no, not at all.
Lauren Crossland-Marr: Really? Why not?
Haruka Nakata: There was also this paper with, uh, came with the tomato and the recipe. And it says that this GABA tomato is the first product that was accepted by the government that were sold in Japan. So I was like, then that should be safe because government accepted it, so it should be good. Or like nothing bad, nothing negative.
Lauren Crossland-Marr: And I understand where Haru is coming from. If the government says it's safe, then why wouldn't it be? But as someone who studies this stuff, I know there's no hard evidence to prove that the genetic change hasn't altered other things in the fruit.
Scientists only have to prove that the specific edit they set out to change worked. That leaves a lot of questions about what happened to the rest of the fruit. We can't say whether it's good or bad, because there's just no data. Scientists don't have to do that work. This is the boring part of the work, as Belinda describes it.
But it is also really important because there could be other affected genes, and in her case there were. And that's where Belinda's concern comes from.
Belinda Martineau: We can't solve the problem until we know more about How the problem manifests itself. So I'm all for doing more science on that, but you know, it's not as exciting to be looking at minimizing the off target effects of your technology than putting a gene of interest in there and seeing what you can do to the plant. You know, nobody wants to do the dirty work of the regulatory experiments, but they're so important.
Lauren Crossland-Marr: In this episode, we've talked about two different gene edited tomatoes decades apart. Both of them are guinea pigs of new gene-editing technologies. When I think about both of them in this context, I think about what scientists can learn from some of the mistakes of the past, so they can build something that is better.
Isn't that what science is all about? Something that is better not just for companies’ bottom lines, though, but also for consumers. Speaking with Haru made me realize we are quite literally consuming this science, and it made me consider something I hadn't before. Should we just be consumers, or should we have more say in the development and application of CRISPR foods?
Haru had no idea what CRISPR was when we first spoke, and most people have never heard of CRISPR, and maybe that's the problem. Even if people don't know about CRISPR, surveys show that people want to know how their food is made. They want labeling. And they want safeguards on the use of gene-editing technologies.
Companies have been using the tomato as a foray into gene edited foods, because it's really common, and many people cook with tomatoes on a daily basis. Companies feel like tomatoes are a way into people's kitchens, and yet they aren't making a meaningful effort to find out what consumers want out of this technology.
Honestly, I wasn't 100 percent sure what CRISPR was before getting started on this project. It can be really technical and confusing, even for people like me who are used to reading complex research papers. And the world of CRISPR is so much bigger than I ever imagined. I want people to know about a technology that will greatly impact all of us, because it's personal.
It's the food we eat, and pretty soon it's going to be on our plates, and you may not even know it. And that's what this whole series is about. Giving you the facts, error bars and all, and letting you decide what to think of this new technology and how it's being used. So join me as we delve into the world of CRISPR innovations, from hornless cattle to protein enriched soy to ask: Who's benefiting and what are the risks?
Would you try a gene edited tomato to relax and unwind? Leave us a review and let us know. And don't forget to subscribe to A CRISPR Bite wherever you get your podcasts.
CREDITS
A CRISPR Bite is supported by the Jean Monnet Network, which is funded by the Erasmus Program of the European Union through the GP3 network of scientists.
This podcast does not reflect the view of our funders. This podcast was co written and hosted by me, Dr. Lauren Crossland Marr. Our executive producer is Corinne Ruff. She co-wrote, edited, and produced the show. Jake Harper edited this episode. The show was sound designed and engineered by Adriene Lilly.
Erin Crossland made our theme music. Rachel Marr designed our logo. Legal support from New Media Rights. And marketing help from our friends at Tink Media. Thank you to the Jeep3 team. Special thanks to Matthew Schnurr, Klara Fischer, and Glenn Stone for their support and advice on this podcast. Also, special thanks to Fumino Tamaki for her help in organizing the Japanese interview.
We'd also like to thank Dr. Belinda Martineau. She wrote an excellent book documenting her experience at Calgene, where she and her team created the first gene edited whole food. The book is called “First Fruit.” If you're interested in this topic, we can't recommend it enough.