Through the winding hallways of the centuries-old University of Leuven in Flanders, Belgium, past the sterile black counters in biological laboratories, buried in the depths of freezers, and suspended in cryogenic slumber, there sleeps a creature feared by the masses.
It's small — microscopic, in fact — but it packs a punch. The creature is barred from entering certain laboratories in the United States to safeguard against contamination. It's feared by the general public as an abomination of nature, an organism whose critics say it was created by the hands of man playing god. The creature is the target of lobbyists and NGOs that would like nothing more than for it to be destroyed. But, is this creature — actually a manmade strain of yeast, a single-celled organism humans have been cultivating for at least 7,000 years — just misunderstood?
Dr. Kevin Verstrepen is a professor of genetics at the University of Leuven, itself located a country steeped in beer history since the first Crusades. But Verstrepen didn't come to the university with an interest in beer. He wanted to figure out the nuts and bolts of how life works, and like many other biologists, he chose the fast-growing yeast Saccharomyces cerevisiae as a model organism for his research. As Verstrepen toiled in the lab, sequencing the DNA of the yeast organisms' genomes to figure out how they evolve, the tastier, boozier potential of Saccharomyces cerevisiae was never out of mind. Outside the lab, this model organism goes by a different name: brewer's yeast. It's the same organism that's used to make bread, chocolate, wine, and beer.
Verstrepen and his team were curious if they could apply their expertise in genetics to the brewer's yeast. Because "every yeast is different in the aromas they make, in the way the beer will taste," Verstrepen hypothesized that the code buried in the Saccharomyces cerevisiae DNA could help explain the myriad magical transformations that happen in beer casks.
Verstrepen's team sequenced hundreds of Belgian beer yeast genomes and used them to reconstruct a family tree of their country's beer. "We can show that the origins of our beer yeasts are some 500 years [old], when the Medieval brewers were for the first time starting to select yeast," Verstrepen says. For safety reasons, drinking in a lab is typically strictly forbidden, but for a project like this, Verstrepen and his team made an exception, thinking they had to take these yeasts for a test drive. "We didn't only make the family tree, we also characterized each of [them]," Verstrepen says, which is a scientifically proper way of saying they brewed and tasted a whole lot of beer. They used the same base of wort, the sweet soup of grains that serve as the precursor to beer, and fermented a batch with the hundreds of yeasts whose genomes they sequenced. The differences were staggering.
Verstrepen thinks he might be able to swap the genes, creating a more efficient yeast with the same expected taste.
Verstrepen cited the example of isoamyl acetate, the banana-like flavor compound produced by some yeast. It's responsible for imparting the fruity aroma in Heineken and Budweiser. Between one yeast and another he found 30-fold differences in the amount of isoamyl acetate produced. The same differences are also present in other yeast characteristics like levels of alcohol production and temperature tolerance.
Armed with his findings about the inner workings of beer yeast, Verstrepen wondered if he could push the envelope a bit further. For example, Trappist brewers trying to make the traditional, malty toffee taste of a dubbel beer are saddled with the yeast they've been using for centuries: Because yeast helps impart flavors that beer drinkers expect, brewers have no choice but to keep using the same strains. They can't swap in a faster, more efficiently fermenting yeast without sacrificing characteristic, beloved flavors. Verstrepen thinks he might be able to swap the genes instead, and achieve the desired compromise. Enter Frankenbrew.
The Dr. Frankenstein of Beer?
Using novel yeast strains created in the lab, Verstrepen believes he can make brewing cheaper and more environmentally friendly. The idea of handcrafting a designer yeast from scratch isn't just a crazy idea dreamed up after one too many rounds at the pub. A new molecular technique called CRISPR — which works like a cut-and-paste tool for DNA — has made this quick and easy. With Vestrepen's insight into hundreds of brewer's yeast genomes, he could pick and choose which genes to add to achieve a new organism with the desired traits.
To prove this concept, Verstrepen tinkered around with the genes responsible for producing isoamyl acetate, the banana-flavored compound. Instead of the normal range from 0- to 30-fold production, Verstrepen tweaked the genome and made a yeast that produced 100 times the normal amount. The resulting brew tasted like "a bit of an artificial banana milkshake mixed with beer," so he's less than convinced he's created the next hit brew in his lab. "It doesn't sound very appealing, and to be honest it wasn't," he admits. "But it was cool to drink as a scientist."
Future applications of this technology could be much more practical, and presumably tastier, too. "Hopefully it will enable us to expand the aroma landscape of beers, or make more efficient yeast," Verstrepen says. "I think the most promising side of these GM [genetically modified] technologies is that you can take an existing yeast that makes the exact beer you want — the perfect Budweiser or Miller or whatever — and you can make the yeast better." With a few snips of the DNA, a deleted gene here, an addition or two over there, you can make a yeast that ferments faster, or is tolerant to higher alcohol, all without altering the taste.
That's good for the brewers, but it's also good for the environment. If brewers could use designer yeasts to make fermentation more efficient, they would waste less energy heating, cooling, and cleaning enormous fermentation vessels. Many companies use "high gravity brewing" to make strong brews that are diluted prior to bottling. If other yeasts could be engineered to tolerate high gravity brewing, traditional beers could be made quicker. The bottom line: "You can make beers cheaper without losing quality," Verstrepen says.
The challenge that Verstrepen faces, however, is that for much of the public and the vast majority of the brewing industry, Verstrepen didn't just create a cloying, milkshake-y beer — he created a monster.
The future of Frankenbrew
For the time being, Verstrepen's creation remains locked away in his lab in Belgium, partially because "consumers in general are quite afraid of it," he says. Beer professionals agree. "GM [yeast] will be very interesting for the scientific community, but I don't think anyone is going to be rushing to use the GMO strains," says Rory Lawton, a Berlin-based beer consultant. "The brewers are keeping themselves honest. They don't want to damage the reputation of this natural product."
Dr. Karen Fortmann, a scientist at the White Labs, a San Diego, California hub of brewer's yeast research, education, and supply, notes that GM yeasts are barred from going anywhere near the White Labs, for fear they'd accidentally infiltrate the carefully curated strains grown there. "We're a long way off from having brewers accept any genetically modified organisms," Fortmann says. "It's not generally something that's wanted in this industry."
"We’re a long way off from having brewers accept any genetically modified organisms."
Despite the trepidation, thinking of "designer yeast's" creative potential is tempting. For example, brewers could use GM yeasts to sidestep outdated laws that limit what they can and cannot brew. The famed 500-year-old German purity law, the Reinheitsgebot, precludes any beer in the country from being made with ingredients other than barley, hops, and water. Ironically, this law was enacted 300 years before microorganisms like yeast were even discovered.
But "there's no mention in the modern regulations about where the yeast come from or what's in the DNA," says Lawton, noting a potential loophole. German brewers could never add popular beer flavor additions like oats or coffee during the fermentation process, but it wouldn't technically break the Reinheitsgebot to use a yeast engineered to churn out those flavors. Furthermore, technically speaking, the finished product wouldn't be GM if the yeast cells were filtered out before bottling, and if the flavor compounds were produced by naturally occurring genes anyway.
But "if there's any such loophole," Lawton says, "the Germans would be the first to shut it down." Indeed, the biggest hurdles to adopting these technologies are the beloved traditions prized by beer drinkers, not to mention the widespread public fear of these technologies.
Despite these fears, this research has piqued the interest of AB InBev, the Belgian brewing powerhouse behind big label brands like Stella Artois and Budweiser, though they're more interested in Verstrepen's work to characterize and catalogue the diversity of wild yeast. For big beer, the GM label is still too taboo. There is, however, some interest among adventurous American craft brewers. The craft operation Mystic Brewery in Chelsea, MA, is co-owned by a fermentation engineer at the biotech company Ginkgo, and they're reportedly experimenting with souped-up yeast.
When asked if beer from GM yeast would hit the taps anytime soon, the answer was a definitive "No." They're still charting untraditional beer territory, but in a natural way: brewing with spontaneous fermentation, where the only yeasts used are those naturally occurring in the local environment. "We're working with flavors that haven't appeared in a beer before," says Louie Berceli, marketing manager at Mystic. By using these wild strains, they're brewing beer with unique New England terroir. "We don't have any plans to work with genetically modified yeast. It takes a bit of the magic out," Berceli says. "There's a whole world of yeast that's yet to be discovered... a certain subtlety and unpredictability in wild yeast. That's the excitement of brewing right now."
For the near future at least, social stigma and legal loopholes will keep Verstrepen's creation from commercial casks. While some craft breweries have asked him to share the GM yeast (many of their names are protected under nondisclosure agreements), Verstrepen has yet to give out his strain. "We're afraid that they might not follow the procedure needed to get clearance to use these," he admits, but goes on quickly to add, "We're quite convinced they're safe, but we do want people to follow the procedures."
Alas, his creation remains behind lock and key, cryogenically frozen in his laboratory, a misfit among the hundreds of tubes of historic Belgian yeasts. For now, it'll have to wait until the beer drinking public is more accepting. "As a scientist," he says, "You have a responsibility not to be a Dr. Frankenstein."
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