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Think of our early human ancestors in the jungle or on the savannah. In a world of grasses, leaves, insects, animals (alive or dead and decomposing), fruits, and dozens of other categories of potential food, they had no automatic knowledge of what was digestible, nutritious, or poisonous. Yet, they had to eat or die. Their vision and hearing, although essential for avoiding predators, were not much help in selecting food, but their sense of taste, combined with smell, provided a critical guide. Many poisonous or indigestible plants are bitter; fruit, with its high carbohydrate content for energy, is sweet; and salt, necessary for human survival, is appealing.
Taste as a guide is not infallible, of course, but it is what evolution has provided to solve the problem of eating the right food. It is a remarkably complex and resilient tool. Today, in developed countries, the challenge of distinguishing the edible from the spoiled or poisonous is less daunting (though far from nonexistent), but taste continues to shape our eating habits and even our relationships in remarkable ways.
In view of this, it is somewhat curious—although understandable—that gustation (the sense of taste) has been labeled one of the “minor” senses, along with olfaction (smell) and somatosensation (touch, temperature, and pain). As compared with the so-called “major” senses of vision and hearing, taste, smell, and touch have been studied less, and, with the exception of pain, have received less attention from physicians. Even among the minor senses, taste has been viewed as relatively uninteresting and insigniﬁcant. Scientists who specialize in the chemical senses, which include smell, taste, and some aspects of somatosensory perception, have been known to quip that “taste is a waste,” whereas “the action’s in olfaction.”
Perhaps taste seems simple in comparison to other senses because it provides information about only a few stimulus qualities: sweet, salty, sour, bitter, and umami or savory. Even the signiﬁcance of the role of taste in perceiving the ﬂavor of foods has been questioned. Most of us have heard the common, but completely unsubstantiated, assertion that 70 to 90 percent of the ﬂavor of food depends on smell rather than true gustatory perception. When it comes to medical attention and research, taste has been given short shrift, in large part because studies started in the 1980s to examine chemosensory disorders discovered that most patients with chemosensory complaints suffered from olfactory rather than gustatory dysfunction. I will explain why this is the case and argue that taste’s very simplicity and relative invulnerability to disruption speak to its critical role as the gatekeeper of the body, protecting us from consuming dangerous substances and encouraging us to eat nutritious ones.
How We Taste
Taste and smell are concrete senses: their receptors respond to what are literally “pieces” of the thing perceived. For taste, those pieces are soluble molecules, called tastants, that can be carried by saliva into the specialized structures that we know as taste buds in our mouths and oral cavity. Each bud contains 50 to 100 taste cells in an onion-like conﬁguration. Most of the cells extend their projections (microvilli) through an opening called the taste pore at the top of the taste bud. It is primarily here that the taste bud makes contact with chemicals dissolved in the saliva.
Taste cells are actually modiﬁed epithelial (skin) cells, but in their capacity as receptors these cells have neuron-like properties. When they are stimulated by a tastant, the cells release one or more neurotransmitters that prompt the taste nerves to send electrical messages to the brain. Not all taste cells are the same; there are several structurally distinct types, and the roles of these various types are not yet clear. It seems likely that some may serve as supporting cells, some may modulate the signals sent by other taste cells, and some may serve as stem cells to renew the population of receptor cells. The latter is a necessary job, because taste receptor cells live only a week or two and must be continuously replaced.
Most taste buds are on the tongue and soft palate, although some are also on the epiglottis, esophagus, nasopharynx, and inside of the cheeks. On the tongue, most taste buds are located in papillae, small projections that give the tongue its rough appearance. Not all these projections have taste buds, however. The most numerous such projections, the ﬁliform or threadlike papillae, lack taste buds. Instead, buds may be found in the fungiform or mushroom-like papillae, which can be seen as pinkish spots around the edges of the front part of the tongue; in the foliate or leaf-like papillae, which take the form of parallel folds along the rear edges of the tongue; and in the roughly 12 (in humans) large circumvallate or wall-like papillae that are distributed in an inverted-V on the back of the tongue.
Taste’s system of communication with the brain is unique: messages are carried to the brain by not one but three cranial nerves. Anatomists label the many cranial nerves (there are 12) as CN followed by a Roman numeral; taste messages are carried by branches of CN VII, CN IX, and CN X. The fungiform taste buds send their messages by a branch known as the chorda tympani; another branch, the greater superﬁcial petrosal, carries messages of the taste buds on the soft palate. Foliate taste buds send their messages primarily by the glossopharyngeal nerve but may also use the chorda tympani as well. Circumvallate taste buds send messages by CN IX. The vagus nerve carries the messages of the epiglottal and pharyngeal taste buds.
The primary gustatory neurons send their long projections (axons) to the brain on the same side of the body from which they originate without crossing over to the opposite side of the brain as do the optic nerves. Reaching the brain, the axons ﬁrst connect with neurons in the part of the brain stem known as the nucleus of the solitary tract (NST). From there, the axons of NST neurons continue the lines of communication by at least two pathways. A reﬂex pathway is conﬁned to the tail of the brain stem and underlies behaviors that are automatically elicited by taste. These behaviors include eating reﬂexes, such as lateral tongue movements and licking, and rejection reﬂexes, such as gagging and ejecting a substance from the mouth. Notably, these behaviors in response to stimulation by taste occur even in infants who lack a forebrain and in laboratory animals whose brains have been cut at the level of the midbrain. The implication, of course, is that these reﬂexes are ancient, rooted in the “old” brain.
The other ascending pathway of NST axons sends information to two higher brain areas. An area in the neocortex (the thalamocortical system) receives taste information from the thalamus. This system seems to be involved in the cognitive aspects of taste processing, such as identifying taste qualities, and appears to be necessary for rodents to learn and remember taste aversions, which are acquired when taste stimuli are paired with gastrointestinal sickness. Another large group of ascending taste axons terminates in the limbic system (which includes the hypothalamus, amygdala, and stria terminalis) and may be involved in what are called affective responses to tastes, that is, the pleasure or displeasure evoked by particular tastes.
Consider three aspects of the gustatory system’s design. The multiple neural pathways by which taste information is sent to the brain reduce the chances that any single, limited injury or infection will close down the whole system. The continuous rapid replacement of taste receptor cells ensures the availability of functional receptors in a system whose purpose requires that its receptors be subject to a constant barrage of chemical stimuli, some of which are potentially toxic. Finally, the relatively low-level, reﬂexive processing of basic taste-elicited behaviors in the brain enables organisms, including humans, to respond appropriately to taste stimuli automatically, without learning or thought. All of these protections suggest a system critical to survival.
What We Taste
The gustatory system detects many different molecules, but it makes only certain discriminations among them. Although the universe of what we taste comprises a wide range of molecular structures, including a variety of ions, small organic molecules, carbohydrates, amino acids, and proteins, we perceive only a handful of distinct qualities. The nature and number of perceived taste qualities have been debated for centuries, but for most of the 20th century scientists generally agreed that they were limited to sweet, salty, sour, and bitter. These were referred to as the basic tastes. One of the greatest misconceptions about taste, which arose early in the 20th century from a misinterpretation of research published in the late 1800s, is the idea that there is a “taste map” on the tongue, with different regions of the tongue being exclusively responsible for detecting different taste qualities. Some textbooks still feature illustrations that depict sweetness being perceived on the tip of the tongue, saltiness along the anterior edges, sourness on the posterior edges, and bitterness at the back.
The truth, as taste researchers have known for many years, is that all taste qualities are perceived on all areas of the tongue that contain taste buds, with only slight regional differences in sensitivity to most tastes. Until recently, however, the actual receptor mechanisms underlying the detection of the basic taste sensations remained elusive. Long frustration with the search for taste receptors no doubt played a role in the relegation of taste to the backwaters of scientiﬁc research, especially at a time when substantial progress was being made in vision, pain, and olfaction.
A breakthrough came in 1999 through the collaborative efforts of scientists from the Howard Hughes Medical Institute and the National Institute of Dental and Craniofacial Research, headed by Charles Zuker, Ph.D., and Nicholas Ryba, Ph.D.1, 2 This ﬁrst step was small but critical, as the researchers isolated a family of two genes that appeared to code for taste receptors, but for which there was no direct evidence of the type(s) of tastes to which those receptors might respond. Soon, however, another member of this family, termed the taste receptor type 1 gene, or TAS1R, was identiﬁed by several different research groups. Further, it was determined that this family of genes produced the three receptor proteins—referred to as T1R1, T1R2, and T1R3—function in joined pairs on taste receptor cells. For example, the complex formed by T1R2 and T1R3 receptor proteins is responsible for most, and perhaps all, sweet taste sensations.
Another intriguing combination, T1R1 with T1R3, seems to function as an amino-acid taste receptor. In humans, its strongest response is to glutamate, familiar to cooks and lovers of Chinese food in the form of monosodium glutamate (MSG). Glutamate is one of the amino acids that make up the proteins in meat, milk, ﬁsh, and legumes. Other receptors may be involved in glutamate perception as well. As early as 1908, a Japanese scientist at Tokyo Imperial University, Kikunae Ikeda, Ph.D., suggested that glutamate might give rise to a ﬁfth basic taste quality, which cannot be mimicked by any combination of the traditional basic tastes. Ikeda termed this taste “umami,” but it is also sometimes referred to as “savory” or simply “glutamate taste.” Umami was not widely accepted as a ﬁfth basic taste, however, until the receptor discoveries of the early 21st century. Thus, basic research in molecular biology contributed to a signiﬁcant revision in our conception of taste quality.
Meanwhile, a large second family of taste receptor genes, the TAS2R genes, was identiﬁed. Humans possess at least 25 distinct TAS2R genes, and, although scientists understand the speciﬁc function of only a few of these genes, this family appears to be devoted to the detection of bitter tastes. Progress is also being made in our understanding of the mechanisms of salty and sour tastes. These two tastes are thought to be elicited by the ﬂow of positively charged ions into taste receptor cells through ion channels in the cell membrane. The channels preferentially admit sodium ions in the case of salt taste and hydrogen ions in the case of sour taste, although we have yet to determine all of the speciﬁc channels involved.
Survival Value of the Basic Tastes
What evolutionary advantages might there have been in the ability to perceive the particular taste qualities that we do?
The calorie-rich carbohydrates, which are an important energy source for most mammals, are naturally sweet, and the taste they elicit is innately pleasant. Even premature infants respond to their ﬁrst taste of sugar with vigorous sucking. We ﬁnd little variation in this basic response to carbohydrate sweeteners, either among species or among individuals of a particular species, although dietary experience can modify preferred levels of sweetness and the speciﬁc sweet foods that are preferred. An exception to this generalization may occur in strict carnivores, which do not rely on carbohydrates for nutrition. Both wild and domestic cats, for example, are indifferent to sweet tastes. Recent work at the Monell Chemical Senses Center in Philadelphia suggests that, although these carnivores do possess all three forms of the TAS1R genes, their TAS1R2 gene (which produces part of the mammalian sweet receptor) has degenerated and no longer functions. 3
Non-nutritive sweeteners of varying chemical composition, beloved of dieters, are able to “fool” the gustatory system. But their ability to stimulate the sweet receptor complex is rather precarious, depending on the presence of speciﬁc forms (alleles) of the TAS1R2 and TAS1R3 genes. Consequently, variation among species is more substantial in response to artiﬁcial than to natural carbohydrate sweeteners.
Humans and all animals require salt (sodium chloride) to live, because sodium is essential to most physiological processes. Today, in developed countries, of course, the problem is excess sodium consumption, with attendant medical problems such as high blood pressure. But throughout history, scarcity of salt has been an issue of survival, particularly for people and animals eating mostly plants, because many plants are low in sodium. Just as with sugar, avid consumption of salt, even in the absence of overt physiological need, is common among mammals, suggesting the preference for saltiness is also built into the taste system, rather than learned.
Although human newborns do not favor consuming salt solutions the way they do sugar, a preference does emerge around four to six months of age. This preference occurs before any extensive exposure to salty-tasting foods, so the emergence of the preference may well depend primarily on postnatal maturation of salt-taste receptor mechanisms. People can modify their salt preferences, but anyone who has tried to stick with a low-sodium diet can attest that it takes time and commitment to reduce preferred levels of salt. It is all too easy to slip back into enjoying highly salted foods, probably because we have a primal pleasure response to saltiness.
Sour taste is elicited by acids, which can be corrosive. It is obviously in an animal’s interest to avoid ingesting strong acids, and studies with human newborns indicate rejection of sour taste is unlearned. For reasons we do not yet understand, how much pleasure we take in sour tastes seems unusually malleable. Infants do reject sourness, but quite a few young children go through a phase when they prefer very sour tastes, and sour ﬂavors are important components of many cuisines. Nonetheless, there are limits, and strong sour tastes, which are associated with high acidity, are almost universally rejected.
All animals need proteins in their diet to grow and repair tissues. As mentioned earlier, the amino acid to which the human umami taste receptor is most sensitive is glutamate, a common component of food proteins. Because umami was only recently accepted as a basic taste by Western scientists, few studies of responses to this taste, particularly in early development, are available. But at least one study of both malnourished and healthy 2- to 24-month olds found a preference for the taste of MSG in soup in the youngest infants, regardless of their health.
The most interesting taste quality may be bitter; certainly it is the most complex. Bitter tastants can take many chemical forms, so a large family of receptors, geared to recognize a variety of structures, is required to detect them. A similar situation is seen in the olfactory system, but a notable difference between smell and bitter taste is that, in smell, the diverse array of chemicals that the family of olfactory receptors is able to detect is perceived to be qualitatively distinct. All of the different molecules that stimulate the family of T2R taste receptors are perceived as being simply “bitter.”
Although they are somewhat controversial, molecular studies of how these families of receptors are distributed yield insight into one possible basis for this difference. In the olfactory system, only one member of the receptor family is thought to be present on each receptor cell: one cell, one kind of smell. In contrast, large subsets of T2Rs can be present on individual taste cells, so one cell may be stimulated by many varieties of bitter tastants. This results in cells that are broadly sensitive to “bitter” but cannot discriminate among different bitter tastes.
What most bitter tastants share is their pharmacological activity and potential toxicity. The key message they convey is: “This is dangerous: do not eat.” Bitterness is an innately aversive sensation, leading to gaping, tongue thrusting, and oral ejection in human newborns (as well as adults) and many animal species. Still, this reaction may be overcome, and a bitter taste may even come to be enjoyed with repeated experience, especially when the stimulus produces desirable physiological effects. Think of coffee, nicotine, and bitter chocolate. In addition, the potential exists for substantial genetic variation in a large gene family, and genetic differences play an important role in individual and species differences in responses to bitter tastes.
Differences among species in both their sensitivity to bitter taste and their tolerance of dietary poisons appear to have evolved to adapt to different dietary patterns.4 Bitter and potentially toxic compounds are much more common in plant than in animal tissues. So strict herbivores—and particularly browsers of leaves, for example—would greatly restrict their dietary options were they to reject all bitter foods. Instead, these animals have developed mechanisms such as large livers to detoxify naturally occurring poisons and have become relatively insensitive to bitter tastes. In contrast, strict carnivores, which are less likely to encounter bitter tastes in their natural diet, can afford to reject anything that tastes bitter, and their sensitivity to this taste is uniformly high. Carnivores also tend to be less tolerant of poisons than are herbivores, devoting fewer resources to detoxiﬁcation.
What about sensitivity to particular bitter tastants? Evidence in mammals suggests the existence of bitter-taste receptor genes common to all species and other genes that only speciﬁc species have.5 Species-general TAS2R genes may underlie receptors that respond to one or more bitter compounds likely to be encountered by many or most species. Species-speciﬁc TAS2R genes, however, may have evolved to produce receptors responsive to bitter tastants uniquely encountered by those species.
Within species, striking individual differences can be found in sensitivity to bitter tastes. In humans, the best-known example of extreme differences in bitter perception is the ability to taste a synthetic compound called phenylthiocarbamide (PTC) and other bitter compounds with a similar chemical structure, such as the isothiocyanates found in Brassica vegetables (for example, broccoli and brussel sprouts). Approximately one in three Caucasians is insensitive to PTC, and, although the proportion of insensitive people varies, all of the many populations tested included at least some PTC-insensitive people. A speciﬁc gene, TAS2R38, on chromosome 7 determines human sensitivity to PTC, and the various forms, or alleles, of this gene have recently been described in detail. They code for different receptors or forms of the receptor that underlie the large individual differences in taste responses.6 Everyday observation certainly conﬁrms that, although we all reject bitter tastes, what we perceive as being bitter varies considerably, putting each of us in a different sensory world.
The Sense of Taste in Health and Disease
Morell Mackenzie, a 19th century otolaryngologist, argued that “while taste is rarely impaired, smell is often altogether lost.” 7 Studies of patients with smell and taste complaints in the closing decades of the 20th century conﬁrmed this. Because the sensory system for taste has built-in redundancy and processes to replace injured components, complete, whole-mouth losses of taste are extremely rare. At the Monell-Jefferson Taste and Smell Clinic in Philadelphia, less than one percent of the patients have experienced severe, generalized taste losses, whereas almost a third have a complete or near-complete loss of smell. Similarly, we have observed less severe forms of taste or smell loss in about 8 percent versus 37 percent of our patients, respectively.8
Substantially more common than simple loss of taste is a disturbing form of taste dysfunction in which there is a persistent unpleasant taste sensation in the mouth. This sensation is called phantogeusia and may be caused by localized neural damage, oral infection, or certain medications. Clinical data indicate that older people are particularly vulnerable to both simple taste losses and phantogeusias that are sufﬁciently long-lived and troublesome to require medical assistance.9 Thus, as our population ages, we may expect a growing number of taste problems.
These problems are serious for reasons that go beyond loss of the pleasure of taste. At the clinic, my colleagues and I have found that taste problems have a greater negative effect on a person’s nutrition than do problems with smell. I have been struck by a common thread in patients’ descriptions of what eating is like after a taste loss; they say that food is like “straw” and literally difﬁcult to swallow. In contrast, although food may taste bland and become uninteresting for patients who have lost their sense of smell, I cannot recall a single one who alluded to difﬁculty swallowing. Patients with taste problems are almost twice as likely as those with smell problems to report weight loss as a result of their dysfunction, and they score signiﬁcantly higher on questions relating to reductions in appetite and food enjoyment.
Aside from actual dysfunction and its health consequences, however, scientists are ﬁnding that normal variations in taste from person to person can have important implications for health. Research in several laboratories is uncovering links between genetic variations in bitter sensitivity, food preferences, and diet. Various alleles of the TAS2R38 gene, for example, are associated with differences in alcohol intake, which tends to be higher in people who are insensitive to PTC and related bitter compounds than in people with moderate or high sensitivity.10 Conversely, children with forms of this gene conveying moderate or high sensitivity to bitter tastes prefer signiﬁcantly higher concentrations of sucrose than do those children with the form that conveys insensitivity. Sensitive children are less likely to name milk or water as one of their two favorite beverages, but have a greater preference for carbonated beverages.11 A hint of the range of possible future discoveries, which came up in that study of children, is the ﬁnding that genetic variations in taste even inﬂuence mother-child interactions. If the mother has no bitter-sensitive alleles, children who do possess them are viewed by their mothers as being much more emotional than those who share her lack of sensitivity.
Is taste a waste? Only if what you eat—or refuse to eat—does not matter. The gustatory system may provide information about only a limited number of the sensory attributes of our world, but those attributes are key determinants of food choice. Many of the chronic illnesses that plague modern society, such as obesity, adult-onset diabetes, and hypertension, derive in large part from poor food choices. Thus, the sense of taste takes on ever greater signiﬁcance as we seek to understand the bases for these choices and to ﬁnd ways to change them.
- Lindemann, B. “Receptors and transduction in taste.” Nature 2001; 413: 219-225.
- Kim, U-K, Breslin, PAS, Reed, D, et al. “Genetics of human taste perception.” Journal of Dental Research 2004; 83: 263-278.
- Li, X, Li, W, Wang, H, et al. “Pseudogenization of a sweet receptor gene accounts for cats’ indifference toward sugar.” PLoS Genetics, in press.
- Glendinning, JI. “Is the bitter rejection response always adaptive?” Physiology & Behavior 1994; 56: 1217-1227.
- Shi, P, Zhang, J, Yang, H, et al. “Adaptive diversification of bitter taste receptor genes in mammalian evolution.” Molecular Biology and Evolution 2003; 20: 804-814.
- Bufe, B, Breslin, PAS, Kuhn, C, et al. “The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception.” Current Biology 2005; 15: 322-327.
- Mackenzie, M. A Manual of Diseases of the Throat and Nose. Vol. II, Diseases of the Oesophagus, Nose, and Naso-pharynx. New York. Wood, 1884.
- Pribitkin, E, Rosenthal, MD, and Cowart, BJ. “Prevalence and causes of severe taste loss in a chemosensory clinic population.” Annals of Otology, Rhinology and Laryngology 2003; 112: 971-978.
- Cowart, BJ, Young, IM, Feldman, RS, et al. “Clinical disorders of smell and taste.” Occupational Medicine: State of the Art Reviews 1997; 12: 465-483.
- Duffy, VB, Davidson, AC, Kidd, JR, et al. “Bitter receptor gene (TAS2R38), 6-n-propylthiouracil (PROP) bitterness and alcohol intake.” Alcoholism Clinical and Experimental Research 2004; 28: 1629-1637.
- Mennella, JM, Pepino, MY, and Reed, DR. “Genetic and environmental determinants of bitter perception and sweet preference.” Pediatrics 2005; 115: 216-222.