by A. Chawla

The Accidental Discovery of the Bitter Taste of Phenylthiocarbamide (PTC)

People can distinguish at least five basic tastes — sweet, bitter, sour, salty and umami. Of these, bitter taste has been the most widely studied. Scientific progress does not always proceed in a logical manner and the serendipitous discovery of two classes of people who differed in their ability to taste a bitter compound is a perfect example.

In 1931, chemist Arthur L. Fox accidentally discovered this trait while synthesizing phenylthiocarbamide (PTC) in his laboratory at E. I. du Pont de Nemours & Co. in Wilmington, Delaware. Some PTC powder escaped into the air, and one of Fox’s colleagues complained of a bitter taste on his lips, but Fox couldn’t taste anything (PMID 16577421). Further investigation revealed two categories of people — tasters and nontasters. This discovery spurred hundreds of studies worldwide to understand the population genetics of this trait and its mode of inheritance.

Evolution and Geographical Distribution of PTC Sensitivity

Tens of thousands of individuals have been tested for PTC sensitivity. Among Caucasians, the estimated frequency of PTC nontaster individuals is ~30% and among sub-Saharan Africans, ~10-20%. Among Asians, nontasters make up 10-20% of Chinese, 10-20% of Japanese and almost 50% of Indians (PMID 18407743). While the reasons for the maintenance of this trait are not clear, one can speculate that bitter taste allowed humans to detect and avoid toxins (PMID 15442282), most of which are bitter. However, at the same time, the high prevalence of PTC nontasters suggests that the nontaster variant must also provide a benefit under certain conditions. Otherwise both alleles would not be maintained at high frequency (PMID 16636110). One theory is that PTC nontasters can taste a different set of toxic, bitter phytochemicals found in indigenous plants of different geographical regions. This would explain the large diversity in nontaster alleles worldwide.

The TAS2R38 Gene Controls Ability to Taste PTC

Although inability to taste PTC was quickly shown to be inherited in Mendelian fashion as a recessive variant in a single gene, nearly 70 years passed before a PTC-tasting gene was identified and characterized (PMID 16636110). A single taste receptor cell expresses a large repertoire of taste receptors, presumably to allow perception of a uniform bitter taste from many structurally diverse compounds (PMID 10761935). Humans possess 25 functional bitter receptor genes, called the TAS2R family.

TAS2R38 is the gene that controls sensitivity to PTC. Three single nucleotide polymorphisms at this locus result in amino acid substitutions at positions A49P, A262V, and V296I, giving rise to the major haplotypes PAV (the taster variant) and AVI (the nontaster variant); other variants in TAS2R38 are rare (<4%) (PMID 12595690). The haplotypes formed by the three SNPs presumably specify functional changes in the protein, explaining the different sensitivities to PTC (PMID 15723792).

Advice for Tasters

Your Pathway Fit test will help you understand your taste genetics. A person described as a taster may be more sensitive to bitter flavors found in foods, such as grapefruit, coffee, dark chocolate and cruciferous vegetables, such as Brussels sprouts, cabbage and kale. However, this does not mean that a taster cannot enjoy these foods. In addition, tasters may need to watch their salt intake, because they may have an increased preference for salty foods, which mask the bitterness (PMID 20380843). Bitter taste is a classic example of how our genetics might explain our food preferences (PMID 21092367).

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