by James Angstman
images courtesy of Calyxt

Dr. Dan Voytas, PhD. Courtesy of Calyxt.

“I just got a text from my 14-year-old niece the other day, and she said, ‘Thought of a good idea for your next genetically modified treat,’” he told me. “So, you see, there’s a difference in the language, right? It’s a GMT. ‘Broccoli and asparagus in one vegetable. It should look like broccoli, but taste like asparagus.’”

That’s my former advisor, Professor Dan Voytas of the University of Minnesota, and he’s a genome engineer. A once-obscure field, genome engineering has quickly hit the mainstream in terms of both its popularity among scientists as well as its press coverage. In large part, that’s due to the development of a class of enzymes called genome-editing nucleases1 that allow scientists to mutate any gene or DNA sequence in virtually any cell type they want. These enzymes work by finding a specific stretch of DNA within the cell – which, among the billions of possible sequences in the genome, is no easy task – and then cutting it, leading to the formation of small mutations at the target sequence. And because even small mutations can often render a gene completely defective, genome-editing nucleases can make a big difference for an organism. Following a recent groundswell of technological development in the area, genome-editing has quickly become a nearly ubiquitous technique across biological research and has garnered quite a bit of press for its potential to cure genetic diseases.

Indeed, most genome engineers – the people who actually work on developing genome-editing reagents – focus their work on problems directly related to clinical applications, and they often find themselves associated with gene-therapy companies. But that’s not Dan’s style. “I was always interested in plant science, and I did my PhD in plant science,” he told me in a recent phone conversation. “And I actually started working in genome engineering to engineer plant genomes. So it’s always kind of been my passion.”

Where others might see the next clinical revolution, Dan sees genome-editing as a better way to engineer crops – commonly referred to as genetically modified organisms or just GMOs – than what has been available in the past. The first wave of GMOs – the kind that can currently be found in nearly every supermarket in America – were produced in a much clumsier fashion than those made through genome-editing. “The traditional GMO, if you want to call it that, is made by integrating some gene – typically not native to the plant’s genome – into the [crop’s] genome,” according to Dan. “This is a random process, and the [DNA] construct can go pretty much anywhere.” If the old way of making GMOs was a hammer, this new method using targeted genome-editing is a tweezers. And that has a lot of implications for how we should think about this new class of GMO products.

The biggest difference is that crops engineered by genome-editing never contain DNA that originated from an external source. “We’re not adding any DNA into the genome. We typically inactivate a [native] gene,” Dan explained. This might seem like a small detail, but it actually makes a big difference in terms of how the plants can be modified. Traditional GMOs, like the famous Roundup Ready crops (see this article), often include genes that have been lifted and transplanted into the crop’s genome from a completely unrelated source (a bacterium, in the case of Roundup Ready plants [1]). Instead, Dan’s work uses genome-editing nucleases to genetically inactivate native plant genes to achieve desired traits. So if a natural crop gene caused the plant to have an undesirable characteristic (like susceptibility to a certain pest), a genome-editing nuclease could be used to remove that trait by disrupting the gene directly, instead of introducing a completely foreign gene to accomplish the same task.

Potato protoplasts expressing green florescence to demonstrate high transformation efficiency. Courtesy of Calyxt.

Because of that difference, genome-edited crops are regulated differently from other GMOs. “The USDA said it falls outside their regulatory purview,” Dan said of plants modified by genome editing, “which means that we’ve created mutations similar to mutations that have been made by [natural processes].” Beyond the USDA, though, GMOs are also regulated by something far more powerful: public opinion. When public distrust of GMO products is so rampant that even mainstream restaurants like Chipotle are eschewing them, people like Dan must concern themselves with PR. And because genome-edited crops fall somewhere in-between natural plants and traditional GMOs on the spectrum of modifications, it raises some interesting questions. Will people still perceive an engineered crop that lacks foreign DNA as a GMO? Yes, they are technically genetically modified, but when those modifications mimic natural genetic variation, does that still make them comparable to Roundup Ready plants?

I asked Dan whether or not he supported labeling GMOs foods – something that 93% of Americans support according to an ABC poll [2] – and he bluntly declared that “people should be informed and be able to make a choice on what they consume.” But once we started discussing whether or not the plants he makes should be labeled, he had to take a moment to think about it. “What do you call a plant with a targeted mutation?” he said finally. “We’ve altered the genome, but we also alter genomes when we [make traditional GMOs]. I’m not against [labels], I just think it’s not an easy question. For the public, it’s too complicated.”

Perhaps it is understandable for him to harbor some apprehension about the topic of labeling, and he does have a point – it doesn’t seem fair for foods that have been tweaked by genome-editing to be labeled the same way as traditional GMOs that contain extra genes. To be clear, Dan does believe both to be safe (“The experiment has been done,” he told me), but he is still cognizant of the need to gain the public’s trust regardless of whether his plants are ultimately viewed as GMOs or something more natural. And on that bigger issue, he has a very clear and perhaps unique approach: the focus must be on the consumer.

“Most of the initial GMO crops were made for traits that really are more or less focused on the farmer,” he told me. “[They were made for] herbicide tolerance… or insect or pest resistance, which is pretty far removed from the consumer. So when we’re using this new technology to create new crop varieties, we’re focused on the consumer.” One of the first products that his company, Calyxt (formerly Cellectis Plant Sciences) has announced is a potato that produces only a fraction of the amount of the neurotoxin acrylamide when fried2. “I can’t explain to my mother exactly what I do and how I make my potato, but if I tell her I can make a potato that has less acrylamide, she might want to eat it over one that has more neurotoxins.” According to the Calyxt website, they are also working on oils with healthier mixtures of fats that could lead to less trans-fat in our diets, and gluten-reduced wheat products, aimed at those with gluten sensitivity. [4]

The Calyxt team in St. Paul, MN. Courtesy of Calyxt.

For now, the products that Calyxt makes are still in trials (these plants need to undergo field tests to make sure they’re fit for agriculture). Whether or not they are recognized by the public as simply another GMO remains to be seen, but genome-edited foods are one day going to be a part of our food supply. Broccoli and asparagus hybrids they are not – not yet at least. But healthier alternatives to what we have now sounds like a promising enough start to me.

1) Namely, these include zinc-finger nucleases (ZFNs), transcription-activator-like-effector nucleases (TALENs), and CRISPR-associated protein 9 (Cas9).
2) Acrylamide is a known neurotoxin and potential carcinogen that has been found in fried foods, including fried potatoes [3]

James Angstman is a fourth year in the Molecular and Cellular Biology Department at Harvard University.

This article is part of the August 2015 Special Edition, Genetically Modified Organisms and Our Food.

References

1. Funke, Todd et al. PNAS. http://www.pnas.org/content/103/35/13010.full

2. Langer, Gary. ABC News. http://abcnews.go.com/Technology/story?id=97567

3. Godoy, Maria. NPR. http://www.npr.org/sections/thesalt/2013/11/19/246188051/remember-death-by-french-fries-here-s-the-story

4. Calyxt. http://www.calyxt.com/

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