Good Beer Hunting

Mother of Invention

Yeast of Eden — Why Genetically Modified Yeast Could Be the Next Step in Beer’s Evolution

The year is 2030. Lagering is a thing of the past because diacetyl has been eradicated. Lambic takes three months, not three years, to make. Most core beers are entirely unhopped, and kettle sours are now called conical sours. Breweries are releasing fresh New England IPAs every three days, and lines still go around the block. 

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Whether that vision is a utopia or a dystopia is up for debate, but all these predictions are certainly possible—and may even come to pass before the end of the new decade. That’s all thanks to advances in genetic modification, which allow scientists to create designer yeasts that can produce all kinds of desired flavors and compounds at minimal cost.

It’s often said that brewing was humanity’s first engineering project. We’ve spent millennia wrestling the process of fermentation into submission, and recent breakthroughs mean we now have an even greater ability to bend it to our will. But one question remains: will drinkers accept this latest innovation?

THE MARSHALL PLAN

Genetically modified organisms—or GMOs, as they’re often labeled—have been around longer than you’d think. The first was created in 1973 by Herbert Boyer and Stanley Cohen, who successfully took an antibiotic-resistant gene from one bacterium and transferred it to another. Within 20 years, the first-ever genetically modified commercial food product was approved: a tomato called the Flavr Savr, which had a longer shelf life thanks to the addition of a gene that slowed down how quickly it began to rot.

The Flavr Savr was divisive, variously hailed as a scientific breakthrough, pure blasphemy, and simply a last-segment novelty on the news. But the producer was eventually acquired by the controversial food and chemical giant Monsanto, and that move tarnished the reputation of GMO for decades.

While lobbyists called genetic modification heretical (and still campaign for it to be banned today), scientists claimed the process was safe and the pursuit worthy. And though the controversy persists, the technology won’t go away—like it or not, genetic modification will become a norm, and within beer it will probably happen sooner than you’d think.

In the case of genetically modified yeast, a big breakthrough was made a little under two years ago by Charles Denby, a researcher at the University of California, Berkeley. He had recently joined the lab run by Professor Jay Keasling, where scientists had been modifying yeasts to produce biofuels and pharmaceuticals for years. His work there gave him an idea—one that combined his knowledge of genetic engineering with a new hobby. 

“I was homebrewing with my buddies and I got pretty nerdy with it,” says Denby. “So I went out to find all the books on brewing science that I could, and I found these results from the 1980s that showed that certain terpenes impart the distinctive flavors associated with classic American hop cultivars.”

Terpenes are organic compounds known for their strong odors, which likely evolved both to attract and deter certain animals. They’re present in a wide array of plants, from cannabis to conifers. If you’ve ever wondered why Citra smells like mango, it’s because the hop and the tropical fruit share high concentrations of the same terpenes.

Using the technology available at Keasling’s lab, Denby realized he could engineer the DNA of brewing yeast to produce these terpenes during fermentation, mimicking the aroma and flavor that would otherwise have been gained through dry hopping. All he had to do was insert the enzymes that produce hop terpenes into the DNA of the yeast. After pitching, as the yeast would begin reproducing and fermenting, it would also produce these compounds alongside the usual alcohol, esters, and carbon dioxide. From a technical perspective, the modification was relatively straightforward, but there was a lot of tinkering to do before Denby’s experiment could become reality.

The tasters were asked, ‘What is your perceived hop flavor and aroma?,’ and the fact that they perceived a much more intense hop flavor and aroma from the beers that didn’t have any dry hop in them was a very significant result for us.
— Charles Denby, University of California, Berkeley

“As it turns out, the enzymes in hop plants are not as efficient as in certain other edible plants,” says Denby. “So we found if we took the same enzyme from a mint or basil plant we were able to get the yeast to produce these compounds much more efficiently.”

Together with other researchers, Denby produced several American ale yeast strains that yielded different levels of Linalool and Geraniol, two terpenes found in hops. He brewed a beer with each strain and planned a side-by-side comparison of them with a standard dry-hopped beer. To make sure the data was valid, he decided to take it to Lagunitas Brewing Company in Petaluma, where brewmaster Jeremy Marshall and his sensory team analyzed the different versions. The results took everyone by surprise.

“It showed that beer brewed with our strains created hop flavor,” says Denby. “The tasters were asked, ‘What is your perceived hop flavor and aroma?,’ and the fact that they perceived a much more intense hop flavor and aroma from the beers that didn’t have any dry hop in them was a very significant result for us.”

Denby’s experiment and results were later published in a paper in Nature Communications, but Marshall wanted to push the technology further. Denby has since continued research through his company, Berkeley Brewing Science, and Marshall is still working with them on customizing yeast strains that don’t just mimic hops, but other flavor compounds too.

“I challenged them to make a yeast that made so much flavor the drinker spits it out,” says Marshall. “They made one that has a very strong semi-wheat-beer profile, coupled with strong cantaloupe notes. We hit it with very strong hops to add coconut and banana flavors, and made it available in our Petaluma taproom. It’s been fun watching people’s reactions.”

Marshall says most people seemed to enjoy the beer, but few ordered a second. The data bears that out—The Marshall Monster, as it was named, has an unremarkable score of 3.71 on Untappd. Still, this groundbreaking beer demonstrated what was possible with this new technology, especially in the hands of brewers. 

BREWING OR SCIENCE?

Berkeley Brewing Science wasn’t the only company to understand the potential contained within edited yeast. Over in Lebanon, New Hampshire, another lab focused on customizing strains to produce biofuels had been experimenting with brewing yeasts. Mascoma LLC is owned by Lallemand Inc., one of the largest yeast producers in the world, so had watched the results of Denby’s research with interest. Robert Percival, regional sales manager for Europe at Lallemand, says there were some concerns at the company around how genetically modified ingredients would be accepted in an artisan industry. The excitement around Denby’s success went some way in allaying those fears, however.

“That was a guiding star for us in a sense,” says Percival. “It was put out there as a study and a concept, and the reception was almost unanimously positive. In the industry and on online forums the reception to the principle of GMO was accepted readily.” 

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With the greenlight from the top, Mascoma started working to find something unique, but still useful to brewers on a large scale. Senior research scientist Chaz Rice was tasked with running the project, and had no shortage of people volunteering ideas.

“Once you start working with beer, everyone gets interested pretty quickly,” says Rice. “People in the lab were constantly throwing out ideas, and one guy had this idea of having yeast produce lactic acid. It was an easy modification, so we made a strain and it produced quite a bit of lactic acid.”

What Rice created has major implications for any brewery producing kettle sours. These beers are mashed like a normal beer, before being inoculated with a souring bacteria called Lactobacillus and left until the pH hits the level the brewer is looking for. Typically, this process takes around 48 hours, clogging up the brewhouse and also leaving the beer open to other infections in the meantime. Rice cut out this step entirely by introducing an enzyme called lactate dehydrogenase (LDH) to a clean ale yeast’s DNA. The enzyme produced double the amount of lactic acid as is typical during the kettle-souring process, with the only trade-off being a drop of around 0.5% ABV in the final beer. 

The additional lactic acid gives the brewer more flexibility to achieve exactly the pH they want, or blend it across multiple batches. The main advantage, however, was something all his brewery test subjects had asked him for during the research phase.

“Nine out of 10 of them were looking for consistency,” says Rice. “Once they make a recipe they want to be able to make it over and over and over. A yeast that can help them do that is something they really want—the cost savings and efficiencies are huge.”

After several successful trials, the yeast was put on the U.S. market in October 2019 under the name of Sourvisiae, and now has over 100 regular buyers. One of those, Rhinegeist Brewery from Cincinnati, Ohio, now makes all its sour beers with the yeast.

“Depending on the level of tartness we are trying to achieve we will use it unblended, or blend in a portion of beer fermented with our house ale strain for something more nuanced,” says director of brewery operations Cole Hackbarth. “It means less time in the brewhouse reboiling wort, with consistent fermentation times and pH levels. There’s also no danger of butyric acid or excessive diacetyl formation.”

Humans have been modifying yeast, bacteria, plants, and animals with selective breeding throughout our history. So far, no one has seemed to care much as long as the beer tastes great.
— Cole Hackbarth, Rhinegeist Brewery

Rhinegeist says it is very open about its use of the genetically engineered yeast, and has received no backlash from customers. That might sound surprising, given the reputation GMOs have, as well as the optics of using lab-generated organisms within an industry that many drinkers believe is about natural ingredients and hands-on processes. But it may also be evidence of shifting consumer stances on genetic modification.

“It is important for people to know what they are consuming and it's our responsibility as a brewer to be transparent about all our raw materials,” says Hackbarth. “But humans have been modifying yeast, bacteria, plants, and animals with selective breeding throughout our history. So far, no one has seemed to care much as long as the beer tastes great.”

MODIFYING THE NARRATIVE

Speaking to the scientists and brewers involved, you will hear a lot of talk about how safe yeast is as a testing ground for genetic engineering. It has been used in the commercial fuel and pharmaceutical industries for years, though the distance between those processes and the consumer is much greater than in beer.

“There has been such a dramatic anti-GMO marketing campaign out there for the last two decades, but I think that has started to wane,” says Rice. “Yeast is a model organism that has been used for a century from a research point of view, and the genome has been sequenced for years.” 

You might think that views would be different when it comes to something you eat or drink, but brewer’s yeast has been designated as safe by the U.S. Food and Drugs Administration, which means releasing modified versions is relatively easy. That’s not true throughout the world, however, and such products are still heavily regulated within the European Union, which is why neither Berkeley’s nor Lallemand’s yeast is available outside of the U.S. yet.

“We got an influx of inquiries in Europe and were inundated with questions about where people could get Sourvisiae,” says Percival. “We had to say, ‘Sorry it’s only licensed for use in the U.S. and would be illegal to use elsewhere.’ That’s not to say they can’t be licensed, but it’s a long, laborious process.”

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Percival hopes that the work Lallemand has done in America will start conversations across the Atlantic and that, when it chooses to launch the product there, the systems and processes will have opened up. Hackbarth agrees that this is only the start of the conversation around genetically modified consumables, and that beer is the perfect medium for it.

“We need to start the discussions around the ethical use of gene editing, and a great place to start is in beer,” he says. “It is a low-risk segment of popular culture available to all classes and cultures. The potential opportunity for innovation through gene editing is too great for our industry to pass by.”

Whether the argument for genetic modification has been won or not, the researchers are pressing ahead. Both Lallemand and Berkeley see no limits as to what is possible. Giving yeast the ability to produce terpenes and lactic acid count among the simplest modifications, and there is a lot more research to come. Exactly what those innovations might be are still tightly under wraps, but both Rice and Denby floated the removal of the gene that produces diacetyl to reduce lagering times, the ability to ramp up or slow down ester production, and the possibility of speeding up alcohol production using the genes found in fast-fermenting Norwegian kveik yeast.

“There are the laws of thermodynamics—you can’t add yeast to a beer and it ferment in five seconds—but within that there is immense potential,” says Denby. “We spoke about hop replacement and that was our thing when we were scientists coming out of the lab, but having talked to hundreds of brewers the message is how can we brew better beer, how can we create value in different ways.”

As if genetic modification weren’t controversial enough, one of the ways in which the Berkeley lab hopes to create value is through engineering yeasts that produce cannabinoids. As cannabis slowly becomes legal at a state level throughout the U.S., Keasling is looking at how to capitalize on its production. He has already engineered a yeast that can convert simple sugar into the high-inducing THC and non-psychoactive CBD in a fraction of the time, emissions, and cost. That could have major implications for the pharmaceutical industry, where THC is used to reduce nausea after chemotherapy and CBD is used to treat seizures in children. But it might have its uses in brewing too, as breweries start to infuse their products with CBD and take advantage of the alleged relaxation benefits and hangover relief.

“I think it’s going to be really interesting to see where this space goes,” says Keasling. “We had someone in from a brewing company who licensed the strain, and we talked to them about how they see it going in the future, and it can go one of two ways: either they use the yeast to produce pure cannabinoids and add it to the drink, or to brew and produce the amount of cannabinoid you want in a single vessel.”

Keasling says they are still doing tests on how alcohol and THC would behave and interact when produced at the same time, but is excited by the prospect. As head of the lab where both the hop compound yeast and his own cannabinoid yeast were produced, he knows the opportunities for modified brewing yeast better than anyone, and is certain it will become the norm in the industry.

“To be frank, when we started this work I just considered it academic,” Keasling says. “I assumed no one would be interested in GMO yeasts, so I’ve been pleasantly surprised. We’ll be able to add pretty much any flavor you want, if we can’t do it already. I don’t see any limits—it’s more what will people accept and what people want.”

We’ll be able to add pretty much any flavor you want, if we can’t do it already. I don’t see any limits—it’s more what will people accept and what people want.
— Jay Keasling, University of California, Berkeley

It would be easy to see bioengineered yeast as a threat to ingredient suppliers and the traditional processes many breweries still adhere to. Certainly, the fact that some of the key flavor and aroma compounds in hops can now be produced quickly, efficiently, and more sustainably than by cultivating the plant could be a cause for concern among hop growers. None of the scientists or brewers interviewed see it that way, though. Instead they point to the fact that hops contain so many other compounds, and that the role that yeast plays in transforming hops’ chemical compounds—a process known as biotransformation—is vital to beer’s character. Removing one would be to the detriment of the other, and the beer itself. 

Rhinegeist’s Hackbarth says we are only starting out on the journey of bioengineering, and that genetic modification is more likely to improve the industry as a whole rather than take down elements of it.

“What makes craft beer so exciting is that it's still just as much art as science,” he says. “You can't just dose in flavor compounds at certain levels and get a beer with the complexity of flavor that brewers currently achieve. Some have tried and they call it hard seltzer. While that has a space in the beverage world, no one is talking about the segment being nuanced and artfully crafted.”

Genetically modified yeasts are a bold new frontier, but in many ways they are just another tool for brewers—an extra way to dial in that beer and make it as complex but drinkable as it can be. The process might take getting used to, but these are small changes to an organism humans have been selectively mutating since we first discovered fermentation. As long as responsible engineering leads to clean, consistent, and delicious beer, odds are lines for new beer releases will continue to go around the block.

Words, Jonny Garrett
Illustrations, Ben Chaplek
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