The first time someone synthesized saccharin, the artificial sweetener in Sweet’N Low, it was an accident. A scientist studying coal tar in 1879 didn’t wash his hands before eating dinner and was surprised to taste a sweet residue from the lab on his fingertips. Same goes for the invention of the sweetener sodium cyclamate in 1937: the unwitting pioneer, who was working on a fever medication, put his cigarette down on the lab bench, and when he picked it back up, he detected something sweet. Both products went on be included in sweetener packets and diet soda the world over. The takeaway: The search for a viable sugar alternative is no modern undertaking (and also, some chemists should probably brush up on their laboratory safety skills).
Non-sugar sweeteners can give food and drink a sweet taste without the added calories, spiked blood sugar, and potential for tooth decay of good old sucrose. Finding an ideal one, then, would be a windfall. But to date none have been quite perfect: they sometimes come with negative health effects of their own, and they don’t taste quite right. But now, with a better understanding of the molecules that deliver a sweet kick, scientists might be getting closer.
Researchers from Washington University examined the molecular structure of a protein made by the stevia plant, Stevia rebaudiana. People have been chewing the sweet leaves of this Central and South American herb for the better part of a millennium, and researchers are now trying to harness its flavor. The researchers’ goal was to understand how the plant synthesizes the molecules that give the eponymous sugar substitute Stevia its sugary taste.
Stevia’s big advantage is that it’s far more potent than sugar, meaning it delivers fewer calories for the same level of sweetness. “It takes two hundred sucrose molecules to equal the same sweetness of one Stevia molecule,” explains Joseph Jez of Washington University, the lead author of the study, published in the Proceedings of the National Academy of Sciences. “At a chemical level, Stevia has more juice.”
The leaves of the stevia plant. (Credit: Aneta_Gu/Shutterstock)
But there’s a not-so-sweet downside to the plant. Multiple chemicals contribute to the stevia plant’s sweet flavor, and the one that’s easiest for scientists to isolate has an unfortunately metallic aftertaste. Now, the team has figured out the 3D structure of the protein that’s responsible for making it. They hope that understanding how the protein works will help scientists create newer versions of Stevia that don’t have an unfortunate aftertaste.
“I [did] some reverse engineering to understand the structure that nature already built,” says Soon Goo Lee, the PNAS study’s first author. “Once we understand how the protein works, we can modify it,” says Lee, who began work on the study as a postdoctoral researcher at Washington University and completed it at the University of North Carolina Wilmington, where he’s now a professor of chemistry.
The team used a technique called X-ray crystallography to find the protein’s structure.
“Proteins are very small, and we want to visualize and see how they work,” says Lee. “We purify it and make a really high concentration, and it forms crystals.”
“You isolate your protein of interest and basically make rock candy out of it,” explains Jez. “When you hit that crystal with X-rays, the X-rays bounce off and create defraction patterns.” From these patterns, scientists can infer the protein’s chemical configuration.
Jez says that he’s tried a newer version of Stevia, which will be easier to make thanks to research like his. “It’s incredible,” he says. “I was floored, I was bracing myself for the flavor, and it was all sweet, no aftertaste.”
The New Sugar
Jez and his team aren’t the only ones synthesizing sweet compounds that originate in plants—for instance, other labs are focused creating sweeteners from extracts of monk fruit, an East Asian member of the gourd family. Monk fruit has been used in Chinese medicine for centuries to treat sore throats, but food scientists are interested in compounds it contains, called mogrosides, that are 250 times sweeter than sugar.
Monk fruit, also known as luo han guo, another option for a non-sugar sweetener. (Credit: Eskymaks/Shutterstock)
“The entire business is moving towards natural compounds,” says Oliver Yu, a co-author of the Stevia paper in PNAS, and co-founder of the bio-manufacturing company Conagen, Inc., which produces Stevia products.
“Plants have evolved the ability to make many, many different compounds during at least 500 million years of evolution (probably close to a million, if not more),” University of Michigan biochemist Eran Pichersky writes in an email.
“Therefore, the repertoire of potential [compounds] is extensive,” says Pichersky, a scientific advisory board member of Conagen who was not involved with the Stevia paper. But, while some, like Stevia, have proven adept at mimicking sucrose, artificial compounds have so far fallen short. “Synthetic sweeteners have failed to give the same sensation as natural sugars, and sometimes have persistent aftertaste.”
While the scientists working on Stevia extoll its virtues, medical doctors take a more nuanced view of its health benefits compared with real sugar and artificial sweeteners like aspartame.
Christopher Gardner, a nutrition scientist and professor of medicine at Stanford University, worked on the nutrition committee of the American Heart Association to study the health effects of artificial sweeteners. “Our stunning conclusion was that we needed more data,” quips Gardner, who was not involved with the Stevia study.
When asked if he’d advise a patient to switch out sugar in their daily cup of coffee for Stevia or something like aspartame, Gardner said that if the patient was already leading a healthy lifestyle, a little sugar would be okay — “I think you should just enjoy that cup of coffee.”