Genetic research is on the tip of telling more about tongue

Monday, July 17th 2000, 12:00 am
By: News On 6

Eating a peck of pickled peppers may be tougher on some tongues than others. For those born more sensitive to certain tastes, doing it can be as intimidating as saying it.

"The pickle will taste a little different to you and me," said neurobiologist Charles Zuker. "To me, it may have an intense picklish flavor. To you, it may have a mild picklish flavor."

By scanning human genetics databases and gathering clues from experiments with mice and flies, scientists like Dr. Zuker are tracing tastes into the genes.

"It is unambiguous that there is a genetic basis for taste preferences," said Dr. Zuker, a professor at the University of California, San Diego. "There is zero doubt."

Understanding taste's biological component won't just help explain why certain foods tempt particular palates. The information may also help companies develop better-tasting medicines, more appetizing low-calorie sweeteners, and health foods that taste less like cardboard.

Besides spicing up the quality of life, taste preferences prevent people from swallowing things like motor oil. By helping people choose what to put in their mouths, taste can bring nutrients in and keep poisons out, said Nicholas Ryba, a molecular biologist at the National Institutes of Health in Bethesda, Md.

"For all animals, it's a very important sense," Dr. Ryba said. "It tells you really whether the food you're eating is good or something you shouldn't swallow. ... It's the last barrier before you take food inside your body. If you're going to poison yourself, it's a very important checkpoint."

Humans can distinguish between at least four tastes: sweet, bitter, salty and sour. A fifth, generally accepted category, umami, describes the taste of monosodium glutamate. MSG is a seasoning used in many prepared foods and Asian dishes.

The bitter taste is an especially important warning signal.

"I truly believe that the sole purpose of ... [bitter taste perception] is to ensure we can detect noxious substances and get the hell away from there," Dr. Zuker said. "You eat the wrong thing, you die."

For years, scientists have known that some people are more sensitive to bitter tastes than others. For example, paper dipped in a bitter chemical called propylthiouracil, or PROP, can elicit a range of responses – from none at all to uncontrollable gagging. And when researchers disable a certain gene in mice, the animals can't taste PROP.

Within the last year, scientists have begun to piece together where sensitivity to bitter taste comes from. In a March issue of the journal Cell, Dr. Zuker's team identified a group of bitter taste receptors – proteins that sit on the surface of cells in the mouth, waiting to latch on to certain kinds of bitter compounds.

Each receptor is like a lock that fits its own particularly flavored key. There may be as many as 80 of these bitter locks, speculated Gary Beauchamp, director of the Monell Chemical Senses Center in Philadelphia, though Dr. Zuker estimated that the number is more like 50. But all bitter receptors send the same message to the brain: Stay away.

Everyone probably has different versions of bitter receptors, Dr. Beauchamp said. Depending on slight variations in form, bitter receptors in some mouths might bind more strongly to certain bitter substances. A stronger bond would make something taste more bitter.

Dr. Zuker's study and one in the journal Nature in April by a group at the Harvard Medical School in Boston were the first to identify bitter receptors in mice and people. Dr. Zuker's group tracked a source of bitter receptors to a gene on human chromosome No. 5.

"This is the most important thing that's been done in taste research in the last decade or so," Dr. Beauchamp said. Understanding what makes a bitter substance taste bitter opens up new possibilities for better understanding the sense of taste, he said.

And now that scientists know how the tongue sends a bitter message to the brain, they can try to understand what happens when the message gets there.

"This is the necessary step for everything else," Dr. Beauchamp said. "People will be trying to figure out how the brain sort of manipulates all this for the next 100 years."

Without the tongue, the brain would have no taste input to manipulate. An adult human tongue measures between 6 and 7 inches long. Along the surface of the tongue and the back of the throat, every hole-punch-sized patch can contain between 60 and 300 taste buds, depending on the person. Each taste bud contains between 50 and 100 cells. That means every quarter-inch-wide circle of mouth space can pack in tens of thousands of cells.

Receptors determine which flavors any given tongue cell will respond to, Dr. Zuker said. A lick of a lollipop, for example, makes cells with sweet receptors fire off sweet messages to the brain, while cells with bitter receptors stay quiet. A sip of grapefruit juice, on the other hand, could call bitter-sensitive cells to action.

The combination of fired messages, mixed with the smell of the ingested material, end up in the brain, which interprets the experience as flavor.

There is still a lot to learn about taste receptors and how they negotiate the hodgepodge of tastes they encounter every day. Some scientists are looking for more bitter receptors. Other researchers have been studying other tastes.

Umami seems to have at least one type of receptor that recognizes it, suggest scientists from the University of Miami School of Medicine. The group has found a receptor in rat taste buds that binds strongly to MSG-like compounds. The finding suggests a similar umami receptor might exist in people, the scientists wrote in the February issue of the journal Nature Neuroscience.

Salty and sour are simpler tastes than bitter and umami, Dr. Beauchamp said. A cell registers saltiness when struck by a charged sodium atom, or ion, half of what makes up a molecule of table salt. When a hydrogen ion charges through, the cell senses sour.

That leaves the source of the sweet sense still a tantalizing mystery.

Scientists haven't yet found sweet receptors in humans. But flies might offer a preview for the origins of the human sweet tooth. In the July 7 issue of the journal Science, a group of Japanese researchers working with fruit flies identified a gene that codes for a taste receptor that recognizes a sugar called trehalose. Mutant flies without the gene continued to flock to other kinds of sugars but ignored trehalose.

Such selective behavior suggests the existence of more than one kind of sweet receptor, said Teiichi Tanimura of Kyushu University, one of the authors of the study. "Now, it will be interesting to see if we can find other sweet genes specific for other sugars," Dr. Tanimura said.

Finding sweet genes in fruit flies also supports Dr. Beauchamp's already firm belief that scientists will soon find receptors that lock onto sweets in people. He suspects sweet receptors are harder to find than bitter receptors because there are fewer sweet ones. While many different, equally dangerous bitter substances lurk in nature, only a few different kinds of sugars exist naturally.

As scientists continue to find taste receptors, opportunities arise for companies to manipulate the way things taste. At the sensory research company Senomyx Inc. in La Jolla, Calif., for example, scientists search for compounds that might block bitter tastes.

One goal is to make better-tasting medicines. Drugs that treat cancer and AIDS are notoriously bitter, which can make a sick person feel even worse, said Lubert Stryer, chief scientific officer at Senomyx. And because many children refuse to swallow their medicine, a new, better-tasting antibiotic could boost pharmaceutical sales.

Taste research also appeals to the booming artificial sweetener industry, Dr. Zuker said. Aspartame, a popular low-calorie sugar alternative, turns off many people with its bitter aftertaste. "If I could eliminate bitterness from aspartame, I would not mind having a one-calorie soda," Dr. Zuker said. "Now, I have a 300-calorie soda."

Other ideas at Senomyx include making soy products taste more like red meat, adding savory tones to dried soup, taking the bitter bite out of some types of coffee, and sprinkling a bitter taste blocker on grapefruit in place of sugar.

While most scientists agree that genes have an important influence on taste preferences, few deny that other factors influence what people like to eat. Sure, on a basic level, people inherently like some tastes better than others, said Linda Bartoshuk, a taste researcher at Yale University in New Haven, Conn. Put something bitter on a baby's tongue, and the baby cries, she said. Give it a drop of something sweet, and the baby wants more. "Bitter is hard-wired bad," she said. "Sweet is hard-wired good."

But, Dr. Bartoshuk added, flavor preferences become more complex as people age. For example, coffee is bitter, but the taste of coffee brings caffeine, which the brain can learn to like.

People also like splashes of culinary variety, Dr. Ryba said. "In the end, humans are different from most animals," he said. "We buy our food in supermarkets. We don't need to use the sense of taste to know if something is toxic or not toxic. We just look at the label. We use our sense of taste for enjoyment."