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5 questions: Monell Center marks 50 years of exploring the senses

Fifty years ago, the senses of taste and smell were underappreciated, understudied. Physiologist Morley Kare decided to do something about that.

Robert F. Margolskee, new chief of Monell.
Robert F. Margolskee, new chief of Monell.Read moreHandout (custom credit) / Handout

Fifty years ago, the senses of taste and smell were underappreciated and understudied.

Science and medicine had made significant advances in vision and hearing. But there were no university centers or research groups studying taste and smell.

Physiologist Morley Kare decided to do something about that. In 1968, Kare founded the Monell Chemical Senses Center, where scientists work to unlock the secrets of taste and smell. How do these senses work? How do they affect nutrition? What about health and disease?

To mark the center’s 50th anniversary, we spoke recently with Monell’s director, Robert F. Margolskee, a molecular geneticist who has made significant discoveries about taste biology.

Tell us about the Monell Center. Why do you focus on taste and smell?

When Monell was founded, it was unique and visionary, totally different from anything else out there. Taste and smell were neglected senses. Morley Kare argued that these were really important senses, and that we needed to understand what they do, how they work, and how essential they are to human health.

Taste and smell are closely linked to nutrition — what we choose to eat, what we reject, how much we eat. They are primal senses. The most simple organisms have a sense of taste or smell, or both, that helps them seek out essential nutrients — foods — needed for life. It’s the same with people. It’s the same with cats and dogs.

What Dr. Kare realized 50 years ago was that things can go wrong. And if there is a mismatch between what our senses of taste and smell are telling us to eat and what we actually should be eating, we can have problems, including overweight and obesity, which then can lead to diabetes, heart disease, and hypertension. Even cancer has a component that relates to what people eat.

So when the center was founded, it was to study the senses of taste and smell, and understand the role they have in nutrition and food choices and their relatedness to health and disease. And that remains our mission today.

Monell was the first to document the prevalence of smell loss. Why is that worrisome, and what is Monell doing to find solutions?

Sadly, as we age, our senses tend to decline. Vision is not as sharp. Hearing is not as sharp. Taste and smell are also declining, although it’s more smell than taste.

But the two are related. When you combine them, that makes flavor. Take a glass of red wine. When you put it in your mouth, you taste sweet, sour, bitter and maybe a few other things. That taste is carried by the tongue. But beyond that, the experience of wine is mostly smell. When you sip it, your mouth warms the wine and releases all these volatile odor compounds that stimulate the sense of smell from inside the mouth.

When you have fully functioning smell and taste, they are combined in our brains, and the resulting sensation is more pleasurable or more compelling than either one alone. But older people, when their sense of smell has declined, often say food doesn’t taste like it used to. So they start compensating and might add more sugar or salt to their food. Smell loss is also a safety issue. Imagine if you couldn’t detect a natural-gas leak, or a fire.

In 1986, Monell worked with National Geographic to develop a smell survey, a scratch-and-sniff test that was distributed throughout the world. It led to some really stunning observations. First, two-thirds of the world’s population had suffered temporary smell loss. That’s astonishing. Think if two-thirds of the world experienced temporary hearing loss or temporary blindness.

Typically, smell recovers. But around 1 percent of people had a permanent loss of smell. More recent studies indicate a higher incidence — about 3 percent of adults over age 40. It gets higher and higher as you pass each decade.

Smell is particularly susceptible for two reasons. One is that the smell receptors are nerve cells, and our ability to make new nerve cells is limited. The other issue is — we talk about our nose being front and center on our face, and it’s true. It’s right out there, dealing with the environment, susceptible to trauma, insult, infection. After a lifetime of that, maybe it’s not a terrible surprise that our olfactory stem cells have trouble keeping up.

So Monell research wants to understand olfactory stem cells and figure out how we can improve their regeneration. The ultimate goal is regenerative medicine — using the body’s own cells to restore functions that are otherwise lost.

When people think of taste, they think of food and eating. But Monell has found that there is more to taste than what happens in the mouth. Tell us about your research on “extra-oral” taste receptors.

Extra-oral just means outside the mouth. Taste receptors are in lots of places in the body. When we first found that out, that was like, “Wow, that’s crazy. Why?” It’s as if you had eyes in your stomach. What is it doing there?

We found sweet receptors in the intestines. They are looking for sugars and carbohydrates, like bread or pasta, that generate sugars. Why? Because your body needs to pay attention to what you’re eating. You don’t want your blood glucose levels to shoot too high; it can cause bad health effects. So sweet detectors in the intestines are coordinating our body’s responses to sugars and carbohydrates.

What about bitter receptors? We’re finding these receptors in the airways — the lungs, and the nose and sinuses. There, they serve a protective function, detecting what might be toxic — a bacteria, virus or pathogen. In the nose, these receptors can stimulate an immune response or a sneezing response. In the lungs, they can stimulate a cough response. This helps us reject a toxic compound or nasty organism.

Tell us about Monell’s efforts to modify cravings for sweet and salty foods, and what that could mean for global nutritional health.

On the current trajectory, it’s proposed that half the world’s population will be overweight or obese within 15 years. That’s extraordinary. Related to obesity, you have diabetes, heart disease, cancer.

We have this problem because humans developed millions of years ago in an environment where there wasn’t so much food. So, we evolved to like sweet and fat.

Today, we need to understand how our biology drives us to consume too much sugar and fat and salt. We know that there is a mismatch between our biology and the environment. We need to better understand what drives the biology so we can maybe make the biological responses more beneficial.

For example, Monell research has shown you can change people’s preferences for salt by changing their diet gradually. By cutting a small amount per week, you can get them down to about half the salt they had in their diet. But on a broad scale, this will require adjusting the salt level in essentially all foods. Our second approach involves molecular biology — by knowing how the taste cells respond to salt, maybe we can trick them so that they will be happy with less salt. We’re doing work like this for salt, sweet and fat receptors.

What is the single discovery from Monell’s first 50 years that you are proudest of or think is most important?

The research about our liking for salt and efforts to modify our salt intake using sensory or behavioral strategies. With that, we can improve global nutritional health by decreasing hypertension and hypertension-related diseases such as heart attack and stroke. This work has formed the basis for current U.S. Food and Drug Administration initiatives to reduce salt levels in food.

We now have similar work going on at Monell with sugar. It could have the same kind of world-shaking effect. If we can change people’s set point for how much sugar they like, we may be able to decrease the amount of empty calories from sugar and carbohydrates, leading to a decrease in obesity and obesity-related disorders like diabetes. This is what I hope will be our next major accomplishment.