WHY YOU LIKE BROCCOLI:
Your genes told you to // Your mother ate it while pregnant // Grandma’s broccoli au gratin
was irresistible // A combination that might someday allow others to like it too
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A Matter of Taste
BY CATHRYN DELUDE // PHOTOGRAPHS BY LEVI BROWN
H
ow people perceive and respond to the
taste of food is largely a matter of evolution. We’re born loving sugar because
it signals the presence of carbohydrates
that fuel the body. We want salt because
it maintains our cells’ electrolyte balance.
Savory alerts us to amino acids, the building blocks of proteins. Bitter warns against ingesting toxic, noxious chemicals
in plants, and sour saves us from spoiled, fermented food. Yet
not all tasters get the same message. John Hayes drinks unsweetened black coffee but shuns grapefruit. His wife loves
grapefruit but abhors black coffee. Their daughter likes both
and sometimes prefers grapefruit to cheesecake.
Hayes is director of the Sensory Evaluation Center at Pennsylvania State University, and based on his research, he thinks
he can relate those varying preferences to underlying biological differences in how tongues detect bitter compounds. Such
innate variations, mostly determined by a person’s genetics,
affect how responsive taste buds are to particular food molecules, as well as how many taste buds there are, and so how
strong a signal they send to the brain. Varying perceptions of
the five basic tastes—bitter, sweet, salty, sour and savory (or
umami, a Japanese word for “delicious”)—affect food likes and
dislikes, which influence our food choices.
Inborn attractions and aversions served humans well when
the most important thing was getting enough food and not being poisoned by it. Yet our needs have evolved, and it would
be ideal now if taste encouraged healthy food choices—rather
than pushing people away from broccoli, for instance, which
some find repulsively bitter, or drawing us to fattening sweets
and carbohydrates. Indeed, bitter compounds also contain
beneficial vitamins, antioxidants and flavonoids.
Scientists have only recently begun to understand how the
tongue, much less the brain, responds to taste and how genetic
variations affect its response. Now, as they trace connections
among taste, flavor and food choices, they’re finding that people’s innate predispositions don’t always predict which foods
they will actually like or dislike, and that environmental factors,
including a mother’s choices passed along in amniotic fluid,
also play a role. As researchers parse the interplay of all of these
factors and their impact on health, some are looking ahead to
a time when it may be possible to entice people toward foods
they are hardwired to avoid and away from others they enjoy to
an unhealthy extreme.
A
large part of the gustatory system, which governs what
and how we taste, is visible on any human tongue.
There are small, mushroom-shaped structures called
papillae that contain globular clusters of taste buds. Each taste
bud in turn has 50 to 150 taste cells, each of which is studded
with proteins known as chemoreceptors that detect only one
of the five tastes. Chemoreceptors bind to a specific type of
food chemical, variously known as a tastant, taste stimulus
or ligand. For example, natural sucrose and similarly shaped
molecules in artificial sweeteners are tastants that connect to
sweet receptors, and when they make their wonted links, they
trigger a reaction that sends a signal of sweetness to the brain.
That message travels along a cranial nerve from the tongue to
the medulla, in the brain stem, which connects to other brain
regions involved in appetite, emotion and cognition.
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taste PTC/PROP predicted how many foods they disliked. But
that observation was largely ignored until the 1990s, when
Linda Bartoshuk, then at Yale University and now at the University of Florida, discovered additional layers of complexity.
Bartoshuk found that some people qualified not only as tasters but as “supertasters,” at the opposite end of the spectrum
from nontasters. Rather than determining whether people
could detect low concentrations of PROP—the acid test dividing tasters from nontasters—Bartoshuk looked at how intensely people perceived higher concentrations. Using sound
and light as a frame of reference, she discovered a wide range of
intensities. “Most of us live in a world of pastel tastes, but about
25% of us have neon tastes,” she says. To those supertasters, bitter is more bitter, salt is saltier and sugar is sweeter—and food
likes and dislikes tend to be more extreme.
B
Scientists knew much less about the physiology of taste 80
years ago, when DuPont chemist Arthur L. Fox made an accidental discovery. Fox was transferring a newly synthesized
compound, phenylthiocarbamide, or PTC, to a container, and
some of the powder wafted into the air. A colleague tasted
something horribly bitter, but Fox detected nothing. Curious,
he gave samples to other people, most of whom also thought it
ghastly. But about a quarter of them, like Fox, found it tasteless.
Fox and geneticist A.F. Blakeslee then took PTC to a scientific
meeting and observed a 2.3-to-1 ratio of tasters to nontasters—
close enough to the 3-to-1 inheritance pattern of dominant to
recessive characteristics, as with Gregor Mendel’s peas, to indicate that nontasting was a recessive trait.
Yet why would humans have evolved in such a way that most
were repelled by a nonnatural substance? The answer, which
didn’t emerge until the 1950s, was that disliking PTC—and a
related synthetic chemical, PROP—was a kind of accident. The
innate aversion of those who could taste those compounds was
to bitter chemicals, called glucosinolates, in cruciferous vegetables such as kale and brussels sprouts (PTC happens to mimic
natural glucosinolates). One glucosinolate, goitrogen, is toxic to
the thyroid in large quantities, so it made sense, in evolutionary
terms, for people to have a sensitivity to it. However, in smaller
amounts, other glucosinolates may help ward off cancer.
By the 1960s, a few scientists had confirmed what the earlier research seemed to predict—that whether someone could
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artoshuk’s work led others to explore how genes influence taste. In subsequent studies, scientists found
that each type of tastant—bitter, sweet, salty, sour or
umami—triggered a different kind of chemoreceptor, and the
observation of differences in how tastes are perceived suggested that those receptors might vary from person to person,
because of variations in the genes controlling the receptors.
In the late 1990s, researchers began to identify those receptor genes, first in mice and then in humans. They knew that
different strains of mice had distinct preferences for sweet and
bitter, judged by how voraciously they would lap up sugar water
of a particular concentration and whether they would shun water laced with bitter compounds. By then, human and mouse
genome sequencing projects were well under way, and in
2000, Charles Zuker, a neuroscientist at Columbia University,
“Taste is greatly affected
by the activity of our
receptors. And because
receptors vary from
person to person, so
does the way we
experience taste.”
working with National Institutes of Health scientists, identified a family of bitter receptors and showed that the mouse
genes for those receptors came in taster and nontaster variants
that resulted in different sensitivities to bitter chemicals.
Bitter receptors (and also those for sweet and umami) belong
to a class called G protein–coupled receptors (GPCRs), with
seven loops that span cell membranes, and have an extracellular extension like a Venus flytrap. This flytrap can bind to a
chemical of a particular shape floating by on the tongue in lockand-key fashion. When a bitter compound fits the lock, that
connection causes the taste cell to send a signal to the brain.
In the early 2000s, researchers used the results of the recently sequenced human genome to identify the human bitter
taste gene TAS2R38, which governs the PROP/glucosinolate receptor. Subsequent studies showed that minute inherited differences in the gene change the shape of the receptor’s binding
pocket—the lock in the lock-and-key connection in the flytrap.
About one in four people (supertasters) receives two genes (one
from each parent) that produce a receptor that binds strongly
to PROP; another 25% (nontasters) receive genes that yield a
receptor that binds weakly, if at all; the rest (mid-tasters)
receive one of each.
Several labs have now shown that these small genetic modifications change the response to taste
compounds, and scientists have engineered
mice to tweak their sweet and bitter genes
and alter their food preferences. “Taste
is greatly affected by the activity of our
receptors,” says Zuker. “And because
receptors vary from person to person,
so does the way we experience taste.”
That means that people live in separate taste universes, and each person’s
individual constellation can have
much to say about overall health.
Yet these genetic differences
alone don’t explain the wide variation in bitter perception, which may
range from absolute distaste to active
appreciation. “We can’t separate high
tasters from mid-tasters with a genetic
test,” says Hayes. And only certain bitter keys—PROP and the glucosinolates
from kale and related vegetables—fit the
binding lock of the protein produced by the
TAS2R38 gene. It turns out humans have, in
addition to PROP, some two dozen other bitter
receptors. At least some of the genes for those receptors also have multiple versions, further explaining the
wide variations in how people perceive different flavors.
Some of the most telling information about how a grab
bag of genetic differences relates to taste comes from a study
published in the March 2011 issue of Chemical Senses. Hayes,
Bartoshuk and their colleagues examined DNA collected from
participants and analyzed the genes associated with several
bitter receptors to create a genetic profile of each participant.
Then the researchers asked the participants to taste samples
of three bitter drinks—unsweetened grapefruit juice, instant
espresso and blended Scotch whisky—and rate the intensity
of each sample. Some participants rated coffee as tasting
twice as bitter as others found it, but not all of those same
participants found grapefruit or Scotch to be exceptionally
bitter. These broad variations arose because there are so many
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genes for bitter receptors, making it possible for each person
to inherit an idiosyncratic combination. Hayes and his team
found that an unknown bitter compound in grapefruit juice,
possibly naringin, triggers the bitter receptor TAS2R19. Alcohol triggers both TAS2R16 and TAS2R38, and coffee may activate TAS2R3, TAS2R4 or TAS2R5.
T
his latest research is helping to explain how particular
genes appear to relate to specific tastes, and the combination of gene variants that someone inherits seems
likely to influence which foods that person will crave or avoid.
But another factor, visible on the tongue, also affects the relative intensity of how tastes are experienced. When Bartoshuk
discovered supertasters, she noticed that they had more papillae than non- and normal tasters. Having extra papillae also
affects the perception of a food’s flavor—a quality that takes
into account the pain of hot chili, the cool of mint, the texture
of whole grains and the “mouth feel” of fat. And it turns out
that papillae contain nerve fibers with receptors for touch—
and those who have larger numbers of papillae, with additional
nerve receptors, tend to experience foods more intensely.
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That’s another reason, Bartoshuk says, that supertasters are
likely to find bitter vegetables, sweet desserts and fatty, creamy
foods unpleasantly vivid. They tend to gravitate toward mild
food, eating fewer ribs, fries and desserts, but also less broccoli.
That diet could give supertasters lower risks for obesity, diabetes and cardiovascular disease but might leave them lacking the
protection against cancer that some vegetables may provide.
While it’s easy enough to test these hypotheses in genetically
altered mice, it’s been difficult to establish definitive connections between high- and low-tasting receptors and human behavioral choices. The evidence that such links exist is strongest
between bitter and vegetables, largely thanks to work by Valerie Duffy, a registered dietitian at the University of Connecticut. In a November 2010 study, Duffy, Bartoshuk and Hayes
directly linked differences in vegetable intake to the TAS2R38
gene. Adults with one or two copies of the taster gene—a group
that, in previous research, experienced more bitterness in vegetables in taste tests—reported eating about 25% less vegetables
than those with two copies of the nontaster gene.
Research on other types of food has found smaller effects,
and none proves that taste genes determine food choices.
Could It Taste as Sweet?//
New compounds that realign perceptions of sweetness and bitterness are nearing the marketplace.
As basic research into taste perception
continues, scientists are exploring practical
uses for expanding knowledge in the field. In
two papers in the March 2010 Proceedings of the
National Academy of Sciences, researchers from
Senomyx—founded in 1998 by Charles Zuker, a
neuroscientist at Columbia University who was
then at the University of California, San Diego;
future Nobel Laureate Roger Y. Tsien, also at
UCSD; and Stanford University neurobiologist
Lubert Stryer—described how they developed
two sweet taste enhancers.
The Senomyx scientists focused on the
extracellular extension of a sweet receptor
protein that functions like a Venus flytrap with
a hinge mechanism. When a sucrose molecule
binds to the receptor, the hinge closes around
the sucrose and activates the receptor, which
triggers a nerve impulse to send a signal of
sweetness to the brain.
But sucrose binds to the receptor rather
halfheartedly, and the signal to the brain is
weak, says Donald S. Karanewsky, Senomyx’s
chief scientific officer. So Senomyx designed
a molecule that enhances the affinity of the
sucrose molecule to the receptor. That sends a
stronger sweet signal to the brain; as a result,
half as much sucrose tastes just as sweet. The
company applied the same approach to make an
enhancer of sucralose, the artificial sweetener
in Splenda, that reduces the amount of sucralose
needed by 75% and softens any aftertaste.
Among the disparate findings are that adult supertasters like
sweet foods somewhat less than others do, but supertaster
children like them more. Among college males, supertasters
are thinner. Supertasters have better lipid profiles, suggesting
lower cardiovascular risk. Older male supertasters who report
consuming fewer vegetables have more colon polyps (a risk factor for colon cancer).
G
enes and the receptors they control are only part of the
equation because they interact with environmental,
behavioral and cultural influences. For example, illness
and smoking can dull taste receptors, Grandma’s home cooking can make you love brussels sprouts, and fast foods can get
you so accustomed to a lot of salt that regular food tastes bland.
So food preferences are not predetermined, and in fact they’re
quite malleable. Both early and late in life, there are windows of
opportunity to modulate proclivities to avoid or embrace particular foods, says Gary Beauchamp, a taste researcher at the
Monell Chemical Senses Center in Philadelphia.
“There’s a huge amount of data from animal studies showing a transfer of flavor via amniotic fluid from the mother to
the fetus, and in rats, pigs and mice, babies will more readily
eat foods their mothers ate,” Beauchamp observes. “We have
found that human babies have similar tendencies.” The same
is true of the foods a nursing mother eats, because flavor compounds dissolve in breast milk. “The foods a woman eats during pregnancy and nursing can have long-term implications for
children’s preferences later in life,” he says.
Adults can also modify their preferences for salts, as Beauchamp demonstrated during the 1990s. Over a period of six to
At Givaudan Flavors in Cincinnati,
researchers have produced a bitter taste
blocker to reduce the aftertaste some people
experience with the artificial sweetener
saccharin. Givaudan reported at a March 2011
meeting of the American Chemical Society
that its scientists had found a compound that
prevented saccharin from activating a bitter
taste receptor. After vetting it for safety, they
gave it to human taste testers, then tweaked the
molecule to make it 10 times more potent.
These and other flavor companies are
working on additional compounds. Some
enhancers and blockers have already made
their way into products on grocery shelves.
Many others are nearing production.
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eight weeks, he gradually reduced the level of sodium in soup
given to a panel of human subjects. In time, the salt concentration the testers had thought was ideal came to be perceived
as too salty. “In theory we could use that approach to shift the
whole population down to levels closer to that recommended
by U.S. dietary guidelines,” he says.
Relearned perceptions of other tastes might one day help
people overcome genetic proclivities—or drugs or food additives could be developed that make healthy but unpopular food
choices more palatable. The goal, says Columbia University’s
Zuker, is “to help people enjoy the things that make our sensory
experiences rich in a healthy, productive way. If we could modulate the activity of taste receptors, we could perhaps help with
serious problems in our dietary world.”
DOSSIER
1. “Common Sense About Taste: From Mammals to Insects,” by David A.
Yarmolinsky, Charles S. Zuker and Nicholas J. P. Ryba, Cell, Oct. 16,
2009. The authors take us on a tour of the tongue and through a series
of animal experiments to demonstrate the “logic” of how tastes are
coded and transmitted to the brain.
2. “Nutritional Implications of Genetic Taste Variation: The Role of
PROP Sensitivity and Other Taste Phenotypes,” by Beverly J. Tepper,
Annual Review of Nutrition Volume 28, 2008. This review provides a
historical overview of the discovery of genetic variations in bitter taste
perception and evaluates the conflicting evidence for a relationship of
genetic variations in taste receptors to food choice, diet and health.
3. “Molecular Mechanism of the Sweet Taste Enhancers,” by Feng Zhang
et al., Proceedings of the National Academy of Sciences, March 9, 2010.
This study of a sweet enhancer demonstrates how researchers can use
molecular biology and drug development to produce new compounds
that can reduce the amount of sugar added to food and block the bitter
taste of medicines, artificial sweeteners and vegetables.
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