Strange Fruit

Long before its intriguing properties were understood, the "miracle berry" got its name. All anyone knew was that if you nibbled a berry prior to eating sour foods, and it had abundant contact with your tongue, tartness would be transformed into sweetness. In West Africa, where the berry is indigenous, and the traditional diet features tart cornbread, wine, and other naturally sour foods, it has served, unsurprisingly, as a popular appetizer.

In the late 1960s, miracle berries began piquing the interest of American scientists. Although the fruit itself isn't sweet, its taste-altering talent offered the promise of reforming the eating habits of a population whose century-long sugar binge was fueling obesity and diabetes. When scientists scrutinized the composition of the fruit, what they found was a protein with taste-altering properties remarkable enough to revolutionize our understanding of taste perception itself. They dubbed it miraculin.

Now, the mechanism that underlies miraculin's effect is getting its due. The molecule, says psychologist Danielle Reed, associate director of the Monell Chemical Senses Center in Philadelphia, spotlights the importance of the biophysical interaction that occurs between the tongue's taste receptors and the food molecules that stimulate the sensation of taste.

Unlike most taste-stimulating molecules, miraculin wears two hats. It is a sweet-receptor antagonist; it binds to receptors (found inside the taste buds) for sweetness without activating them and renders itself relatively tasteless. It is also a sweet-receptor agonist, activating the receptors and sending instructions to the brain, via a neural signal, to perceive the current flavor as sweet.

Under normal conditions, miraculin acts as an antagonist. But as soon as there is a drop in pH—the presence of an acid in the mouth—it switches hats: It undergoes a structural change that turns it into an agonist. Suddenly, vinegar tastes like syrup, sour maize bread tastes cake-like.

Intriguingly, the protein remains bound to sweet receptors for up to an hour, allowing the sensation of sweetness to be restimulated any time acidic food or drink is consumed in that period.

Its unique action—the switching between agonist and antagonist depending on the acidity of its environment—opens a novel window into the nature and nuances of human sensory perception. Perhaps most illuminating is researchers' discovery of a perceptual butterfly effect: Just two of the 191 amino acids that make up miraculin—both of them histidines—prompt a change in configuration of the whole molecule, which then turns on the sweet-taste receptor, totally altering the taste of food.

"When it comes to receptor binding," says Reed, "shape is key. Even a minuscule tweak in the shape of a protein can beget a dynamic difference in its binding kinetics, which translates into huge perceptual effects."

Although they constitute a mere one percent of the amino acids in the miraculin protein, the two histidines exemplify a common scientific fact: The function of a large protein may hinge on a tiny constituent within its long polypeptide chain.

It takes little imagination to envision the potential miraculin might have as an artificial sweetener. And indeed, in the 1970s it was on track to be deemed "generally recognized as safe" by the FDA, which would have opened the door to commercialization. But in 1974 the FDA revoked its support, and the cost of testing subsequently needed to prove miraculin safe and effective deterred manufacturers.

Still, the berry has found a niche market. Turning sour to sweet is just the tip of miraculin's perception-altering iceberg. It appears to be able to jump-start taste perception de novo. For Stanley Prager, miraculin's effects have meant the difference between tasting something or nothing at all.

Food, Prager says, "was one of my great pleasures in life." But in 2015, he was diagnosed with carcinoma at the base of his tongue and began radiation and chemotherapy. His ability to taste food disappeared, and every meal became a struggle to get down. Prager read about the Miracle Fruit Farm in Miami, Florida, established in 2012 specifically to grow the tropical fruit. So he sent for some berries and then paired them with a glass of wine.

"To my absolute astonishment, I could taste the grapes," Prager found. His taste receptors, which had grown insensitive to ordinary foods, were activated by miraculin.

Miraculin is still not widely available—just a few farms now grow the berry in the U.S.—but it is gaining a robust reputation in the cancer world, helping chemotherapy patients maintain appetite and quality of life. The anecdotal reports of patients like Prager found their way to oncologists, and in 2012 a pilot study tested the effect of miracle fruit on the eating experience of eight cancer patients.

The eight unanimously found that miraculin made their food highly palatable, a result that holds promise for patients afflicted with altered taste perception due to chemotherapy. Losing the ability to enjoy a meal is no trivial side effect of cancer treatment; it can easily lead to malnutrition and threaten survival.

Exactly how miraculin turns on taste in cancer patients is not yet fully understood, but hypotheses focus again on the protein's structure. Research suggests that miraculin's configuration gives it a particularly high affinity for sweet-taste receptors. As it passes over the tongue, the protein has a greater tendency to bind to sweet-taste receptors than do many other sweet molecules, which could explain its power to trigger the receptors when other molecules cannot.

"At first, chemotherapy patients were trying it just to experience its effect," reports Kris Tietig, co-owner of the Miracle Fruit Farm. "But more and more folks are making it part of their lifestyle."

Since 2012, the farm, which ships nationwide, has doubled its output. While the berry has by far the strongest taste-altering effect, Tietig is developing other formulations—juice, tablets, powder—that maintain potency while getting around the short shelf life of the fruit itself.

A Sweet Solution?

Could miraculin accomplish what artificial sweeteners haven't—avert the most devastating consequences of America's sweet tooth, obesity and diabetes? Synthetic sugar substitutes have been able to mimic the taste of sugar without a large helping of calories, yet health statistics remain on a troubling course. Danielle Reed of Monell Chemical Senses Center is skeptical: "We have many high-potency sweeteners that have few calories, and they don't seem to have made a dent in obesity or diabetes rates."

Food manufacturers continue to do everything they can to make their products appealing and hide sugar in improbable places—sauces, bread, soups. Often it masquerades as maltose or high fructose corn syrup, or any of 60 other aliases.

But in the effort to lure consumers away from sugar-saturated groceries, scientists have begun trying to genetically engineer miraculin into common produce, giving consumers a shot at having something healthy at hand to satisfy their next sugar craving. Until consumers are willing to trade in their sugar-studded snacks for more savory alternatives, miraculin could allow them to have their cake without eating it too.