You've probably heard about the gene-editing technology CRISPR. The massive biotech breakthrough, which has emerged in the last decade, has mainly been touted for the ways it will let scientists edit the human genome — hopefully to cure genetic diseases or perhaps, more worryingly, to create "designer babies." But CRISPR is also being used in another area, the world of food.
Cultural anthropologist Dr. Lauren Crossland-Marr hosts the five-episode podcast A CRISPR Bite. She takes listeners into labs as researchers tinker with the genes in what we eat and drink. What, exactly, are they trying to achieve? And what's at stake?
Evan Kleiman: This is just so fascinating that you've chosen this as a way to do an incredible deep dive. I'm wondering if it's inspiring or horrifying?
Lauren Crossland-Marr: Well, I hope by the end of the conversation, it's both.
What exactly is CRISPR? I've sometimes heard it called DNA scissors. I'm sure a lot of us have heard about it but don't exactly know what it is or what it does. Can you give us a very basic layperson's explanation?
You've probably heard of GMOs, and your listeners probably have, as well. CRISPR is another more advanced gene technology tool that allows scientists to precisely edit DNA in living organisms. As you mentioned, it acts like molecular scissors. It cuts the DNA at these targeted locations. Obviously, there are a lot of uses for this technology. Many people may have heard of the potential for treating genetic disorders like sickle cell disease or the controversial "CRISPR babies." But it's really important to know that most of us will actually encounter CRISPR through the food on our plates, not at the doctor's office.
How long have researchers been experimenting with CRISPR and food? Pretty much right from the beginning?
That's a really interesting question because CRISPR was first discovered in yogurt bacteria in the early 2000s, so its origins are really tied to the food system. With this, many scientists have started applying it to many different types of living organisms. We've really seen a genetic revolution in the past 10 years, using CRISPR to make changes to lots of different foods.
In 2012, Jennifer Doudna and Emanuelle Charpentier invented its use to genetically alter other living organisms. It hasn't been that long but we've seen quite an uptick in its use across the board, not just in the medical sciences but, again, in our food. Scientists are using CRISPR in many different ways — to add nutrients to plants, like more protein to soy, also to decrease pests to protect things like the wine industry. Scientists are now learning a lot more about off-target changes and how to catch them when using this technology. So it's really been a boon in the past 10 years.
Cultural anthropologist Dr. Lauren Crossland-Marr takes listeners into labs to understand gene technology. Photo courtesy of A CRISPR Bite.
We have to go back to the yogurt thing. Did scientists discover that genes were being cut naturally and were able to wrestle that and control it? Or was yogurt the first product that they experimented on with this technique?
They actually discovered CRISPR in yogurt. Basically, CRISPR acted like an immune system for the bacteria in yogurt. It changed coat when it needed to fight off viruses. You can think of this as a naturally occurring CRISPR. In 2012, we see the advent of its applications to all living organisms. That really big leap, from the early 2000s to 2012, is the marker for when we start seeing it used in pretty much everything.
When I think about scissors or I think about cutting up DNA. Because of that word "cut," I'm also thinking "paste." Are most of the applications deleting something or inserting something?
It can be both. Essentially, it consists of this kind of guide, RNA. Thinking back to your biology class, it's just a way that you can design an experiment to match a specific DNA sequence using a protein, the Cas9 protein. So those scissors go in and cut, and they can add and delete at a targeted location.
Let's go into a specific example. The first episode of the podcast you host, A CRISPR Bite, gives us an overview of the tech. Then, each episode focuses on a different food item, starting with tomatoes. You talk about how a company in Japan used CRISPR to develop tomatoes with increased levels of GABA, which is an amino acid that's been shown to decrease stress. Can you talk about this particular example and why it's significant? And maybe also a bit about how tomato genetics have been edited way before CRISPR?
The tomato is so interesting in the history of genetic engineering because it was the first plant really modified and put on the market using both GMO technology and CRISPR technology. For the GMO technology, this was done in the '90s in the US. You mentioned the GABA tomato, which was put on the market in 2021 in Japan. It turns out that tomatoes are relatively easy to modify, which is always a good thing, and they have a huge market. So it makes sense that companies would want to focus on that plant. What's interesting, though, in the use of this technology, gene editing technology with tomatoes in the past, and more recent applications with CRISPR, is that the ways they modified this plant were completely different.
In the '90s, Calgene, the company that created the first GMO tomato, created this tomato that would last longer. They called it a Flavr Savr tomato. You could pick the tomatoes when they were ripe and ship them to markets across the US. This is very different than the new tomato that we've seen from Sanatech Seed, which has added GABA [to tomatoes] to reduce stress. This is an example of adding nutrients to a plant. It could have a huge impact for solving big issues, like malnutrition, across the globe. But at this point, it's sort of like, I would say a proof of concept. No one is going blind from not having enough GABA, like you would with a deficiency in vitamin A. So I still think we're a long way from it having a substantial societal impact. But it's interesting nonetheless.
How did these CRISPR-edited tomatoes, the ones that had higher levels of GABA, affect the Japanese people who ate them?
My best friend's cousin, who lives in Tokyo, did a taste test for us. It was very exciting for somebody like me but also a little disappointing. In the end, she said that they tasted like a normal tomato, they were just a little more sour. And she said that they didn't really make her feel less stressed. I haven't seen any research on their impact on stress levels among consumers, so we're not sure.
I think of CRISPR as a subset of GMO. Is that correct? Would they count as a GMO?
This is really a great question and, surprisingly, this is up for debate. I should say that, to me, it's pretty clear that both CRISPR and GMOs are forms of gene editing. You're modifying the genes to make changes that likely wouldn't happen so quickly, or at all, through breeding. However, proponents say CRISPR is a more natural process, since you're staying within the same genome, unlike with many of the GMOs, which are taking genes from other organisms. The USDA actually agrees and doesn't regulate CRISPR as closely as GMOs, calling it, in some cases, equivalent to conventional breeding.
What about labeling? Have we gotten there yet? I know labeling is still an issue with GMOs.
Yes, this is a big issue with CRISPR, as well. Right now, we don't have labels. It's not necessary. Those people who are concerned about CRISPR and its use in food, really, really want labeling. And that makes sense. In fact, in our first episode, we talk about how there's been a public opinion survey that shows that the majority of Americans would love to have labeling as well, so it seems like a no-brainer. We see it also in the grocery stores with GMOs. Those are often labeled as "GMO-free" and things like that. It would be great if we could get different CRISPR plants also regulated that way but, at the moment, it's not a necessity.
Are there concerns that when scientists altered the genetics of the tomatoes to increase the GABA levels they were potentially altering other things that might somehow harm humans?
This is a major concern for those cautious about using the technology in the food system. After learning as much as I have, I think harm to humans is a possibility, more likely in plants than in animals. With animals, we see that they would be visibly sick, in most cases, whereas plants can be harmful to humans without looking sick. I'm thinking about the many pristine mushrooms that can kill us.
But the main issue is that under the current regulation, as I mentioned, it's not required to check changes across the whole genome. Scientists can show that the changes they set out to make worked without comparing it to the full genome of a normal vegetable to see if there were any off-target changes. In addition to labeling, this is a huge issue and very alarming to those who are concerned about CRISPR in our food system.
"A CRISPR Bite," a five-episode podcast, focuses on how gene editing technology is being used to manipulate tomatoes, wine, and cattle. Logo design by Rachael Marr.
The wine industry, particularly here in California, has been fighting so many fights with climate change, with fire seasons getting longer and much more explosive. You explore how CRISPR isn't being used to alter grapes themselves but to alter the glassy-winged sharpshooter, an insect that's a major pest. Could you tell us about that?
It's a really interesting case because we see that it's being used on the pest and not to create disease resistance in the plant. I think there's a number of factors for that. One that I'll highlight here is that I think people in the wine industry are pretty adverse to GMOs. They're much more likely to be interested in organic wines. With that understanding, these researchers at UC Riverside have really done an interesting job of trying to address this issue of the glassy-winged sharpshooter. An estimate from 2014 found that these pests are costing California vineyards more than $100 million a year. It's originally a pest from the eastern United States. It spreads something called Pierce's Disease. It's a bacteria that usually destroys the entire vine. These little insects aren't ravaging directly but they're leaving this bacteria in the soil, and it can ruin vines for many seasons.
Finally, there's cattle. How are CRISPR researchers trying to modify cattle?
I should note that the hornless cattle project actually used TALEN, which is a technology very similar to CRISPR. In the episode, we highlight this experiment to create hornless cattle. You and many others may be asking, "Why modify cattle this way?" When I started on this project, I thought the same thing. Most cattle have to be manually dehorned so they don't hurt other cattle or their handlers. This is not a fun process for the animals or the people involved. There was a push from UC Davis, from this one researcher, to do this experiment. The cattle from these experiments actually became mini-celebrities. One was actually on the cover of Wired magazine. They really showcased for the first time, publicly, the potential of these newer technologies like CRISPR and TALEN.
When we start using CRISPR to edit the genes of animals, like cows, what ethical issues come into play?
This is such an important discussion point when we think about this new technology. In terms of ethics, I think there are a few guiding questions that map on to what we were hoping to do in the podcast, writ large. I think the first question is: Is the technology as precise as promised? We learned in the episode that the animals that we met were dispatched shortly after finding an accidental change. I think this brings into light animal welfare issues, creating animals in labs, etc.
Second, we need to ask: What are the business interests at play? Are hornless cattle going to address big issues that we have, like climate change? I'm really suspicious that engineering cows to be hornless is a good use of the technology if those changes support unsustainable factory farm systems.
I think the third thing that we can really think about, and it's something that we've talked about already: What might responsible regulation look like, especially for animals? I think we can take a page from the book of medical sciences, who, on the whole, have done a really excellent job of being cautious when applying CRISPR to humans. I think we could take a similar, though perhaps not as extreme, approach. Because in a sense, like with humans, we are modifying generations of animals so these traits get passed down. So we have to think in these long-term ways.