TARGETING TASTE

The Baltimore Sun

Like most natives of Japan, Hiroaki Matsunami has a taste for umeboshi, the super-tart pickled plums Japanese children carry in their school lunchboxes.

Nestled on a bed of white rice, the red orb evokes the sun on the Japanese flag. Nestled on the tongue, it elicits a puckered face.

"I like it, even though I haven't eaten it in a while," said Matsunami, now at Duke University in Durham, N.C., where the potent plums are hard to find. Instead of eating the plums, Matsunami spends his time at Duke trying to figure out how his tongue knows they're sour.

Last month, Matsunami's research team and a separate group of California scientists reported that they've found, at long last, the tongue's tart sensors - molecular docking stations that recognize acidic food particles and send the brain a "sour" message.

The discovery comes eight years into a wave of research into our sense of taste that has answered some long-standing questions and helped dispel at least one myth about the tongue's geography.

Such knowledge may lead to new additives that could make bland foods and unsavory medicines more palatable. It may also explain how tongues, like fingerprints, are unique, making some people sensitive and others numb to certain tastes.

Scientists have long known the surface of the tongue is covered with taste buds - onion-shaped bundles of cells that stand sentry for the digestive system.

Long before the Food and Drug Administration and our modern world of supermarkets and restaurants, taste buds served as a crucial daily survival tool for our ancestors.

The bitter flavor of a wild almond told an ancient human foraging in African forests that the nut was poisonous. A sweet fruit, though, was safe to eat and full of energy. The presence of lions and other man-eaters also added urgency to meal choices.

"If the thing didn't taste good, you might decide it's not worth it to be out in the open and at risk," said Steve Munger, a taste researcher at the University of Maryland School of Medicine.

Much of what we "taste" in everyday life is actually the work of our sense of smell. The tongue can distinguish only five basic flavor sensations - sweet, sour, bitter, salt and umami.

"Bitter is supposed to be a warning that there is something poisonous you should spit out - beer and coffee not withstanding," Munger said.

Umami, the "savory" taste of meat and cheese (also found in the food additive MSG), points to protein. Sweet tells us something is full of carbohydrates. Salt signals, well, that it's salty, and we need a certain amount of salt to survive.

Sour taste comes from acidic compounds, and, like bitter taste, it can be a signal to pass on rotting meat or vegetables. Unpleasant tartness in unripe fruits comes from too much citric acid. It is the plant's way of keeping hungry diners at bay until its seeds mature enough to travel - via the diner's digestive system - to a new home.

Unlike animals, humans have acquired a taste for tartness. In the case of umeboshi, the plums are harvested when still green and sour, before the tree turns them into a tantalizing snack for animals by pumping them full of sugar. (The plums' red hue comes from an herb added during the pickling process.)

Sour cream, yogurt, lemonade, gorgonzola cheese and other tart treats are eaten everyday by millions. Sauerbraten and sauerkraut serve as counterpoints to bitter Oktoberfest beer.

Lots of children love Super Mega Warheads, Sour Bolt Blast Jolly Ranchers and other sour candies, but, as UM's Munger points out, "some people like to go really fast on motorcycles, too."

A decade ago popular myth held that separate areas of the tongue were responsible for each taste. Referred to as the "mouth map," the concept probably originated with a German text mistranslated into English at the beginning of the 20th century. As recently as 1996, mouth map diagrams still appeared in college neuroscience textbooks.

By the late 1990s, however, scientists had learned enough about molecular biology to turn their sights on taste in a big way. They knew that thousands of taste buds cover the tongue, each containing 50 to 100 taste cells. Each cell has two poles: one end covered with taste receptors projecting from the tongue's surface and one end inside the tongue that connects to the brain via nerves.

When a person bites into an umeboshi, or a lemon, or a kraut-covered hotdog, acidic molecules from the food bump into acid-sensitive taste receptors, activating a taste cell, which sends a sour signal to the brain.

The details of this exchange were long a matter of debate. In line with the "mouth map" concept, some scientists believed the taste buds in different areas of the tongue were filled with cells of only one type: the tip with sweet-sensing cells, the back with bitter-sensing cells, and so on.

Others suggested the location of cells wasn't an issue because each cell could sense all five tastes.

However, no one had identified any of the taste receptors, so which cells responded to which tastes was unknown.

Zuker and others set out to solve this problem with a variety of biological techniques, including engineering mutant mice that lacked certain receptors and could not sense certain tastes. They eventually isolated the first taste receptors - those for bitter and sweet.

Each taste cell, they found, is covered with receptors for only one taste. A sweet cell, for example, is only turned on by sweet molecules because it only has sweet receptors. This dispelled the notion that all cells could sense all tastes.

To confuse matters, however, they found that sweet-sensing cells appear to have only one kind of receptor, while there are 25 to 30 different receptors on bitter-sensing cells.

"There are a lot of them," Munger said, "because there are many bitter things you want to avoid out there in the environment."

The scientists also assembled more evidence against the "mouth map" myth when they found that each taste bud contains a full complement of taste cells. "There are areas of emphasis," Munger said, "but there are not these absolute divided areas." Over time the researchers identified the receptors for sweet, bitter and umami. But until a year ago, salt or sour receptors remained elusive.

In July, researchers at the National Institutes of Medicine reported finding a taste receptor that most likely responds to sour or salt. Last month, Zuker's group reported linking that receptor to sour in the journal Nature, while Matsunami's group published a similar finding in the Proceedings of the National Academy of Sciences.

One surprising finding: the sour taste receptors on the tongue are also found in the spinal cord, where they probably monitor the acidity of cerebrospinal fluid. Similarly, sweet and bitter taste receptors have been found in the intestinal tract.

Taken as a whole, the identification of various taste receptors illuminates a key link between the mouth and the brain. It also provides a new target for manipulating the taste of food and medicines.

In the past, artificial flavorings were often chance discoveries. For example, both aspartame (sold as Equal and NutraSweet) and saccharin (Sweet & Low) were identified as sweeteners when chemists accidentally got some of the powders in their mouths.

Knowing the identities of taste receptors, experts hope, will enable a more methodical approach to developing artificial flavors.

"Many people don't like the taste of artificial sweeteners," Zuker said. "If we understand how the system operates and the receptors that control it," he said, we might be able to come up with better ones.

"If you know the salt receptor," he added, "perhaps there are ways to have a small amount of salt to activate it in a way that is still enjoyable."

New molecules might also be developed to cling to bitter or sour taste receptors and block the unpleasant taste of medicines, such as the malaria drug quinine, or children's cough syrups, experts said.

Scientists also believe that differences in the number and types of taste receptors in people's mouths probably make some people more or less sensitive to certain flavors, including sour.

"The right level of sour is determined by the tongue of the beholder, "said Stephanie Moritz, a spokeswoman for the Hershey Co., which makes Jolly Ranchers candy. "The discovery of the taste receptors ... may help us understand individual differences in sour preferences."

In the future, Matsunami and Zuker hope to unravel the complete chain of neural taste and smell circuits that turns a tart umeboshi in the mouth into a tart umeboshi in the mind.

"Now we understand how the tongue knows," Zuker said, "the next question is how does the brain know?"

chris.emery@baltsun.com

GREAT MOMENTS IN TASTE

ca. 100 B.C. -- Ancient Romans make an early artificial sweetener by boiling down grape juice in lead containers. The result is sapa, a sweet, aromatic syrup that added flavor to other dishes but made them highly toxic.

1878 -- Johns Hopkins University chemists Ira Remsen and Constantine Fahlberg synthesize saccharin, the first commercially produced artificial sweetener (commonly sold now as Sweet & Low). Fahlberg discovered the compound's sweet flavor after accidentally getting the powder on his dinner rolls.

1909 -- Japanese chemist Kikunae Ikeda reports extracting monosodium glutamate (MSG) from seaweed, leading to discovery of the fifth sense of taste, umami, often described as "savory" or "meaty." He was tipped off to MSG when he noticed the broth of udofu, a simmered tofu dish, was especially delicious.

1965 -- While attempting to synthesize a new ulcer drug, American chemist James M. Schlatter licks his finger and stumbles onto aspartame, a widely used artificial sweetener now sold as NutraSweet and Equal. The powder is 180 times sweeter than sugar.

1968 -- Kenzo Kurihara, another Japanese chemist, isolates miraculin, a taste-altering compound which, when applied to the tongue, makes sour foods taste sweet. The molecule is derived from small, tasteless red berries on the miracle fruit plant, a West African shrub (Synsepalum dulcificum or Richadella dulcifica).

[CHRIS EMERY]

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