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Authors: John McQuaid

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So-called Mendelian traits—characteristics based on variations in a single gene—revealed the actions of genes to the naked eye. They are rare in humans; in Fox's era, eye color and blood types were thought to be Mendelian, but they later turned out to be more complex. Now Fox had found a new one. He put the word out immediately, placing news of the discovery that some people were “taste-blind” for a substance, and others weren't, in
Science
magazine. He began a series of taste experiments. “It was established that this peculiarity was not connected with age, race or sex,” he later wrote in a seminal scientific paper presented to the National Academy of Sciences. “Men, women, elderly persons, children, negroes, Chinese, Germans and Italians were all shown to have in their ranks both tasters and non-tasters.”

In 1932, Fox had a voting machine installed onstage at the annual conference of the American Association for the Advancement of Science, the nation's premier scientific organization. He invited members of the audience to taste PTC powder and pull the lever for their preference; 65.5 percent were tasters, 28 percent non-tasters, and 6.5 percent detected
other qualities. This showed that the gene or genes for PTC tasting—and a greater sensitivity to bitterness—were dominant, like those for Mendel's purple flowers. The genes for non-tasting, or insensitivity, were recessive, like those of the white flowers.

A scientific craze was born. Scientists fanned out across the world to conduct taste tests on people of different ages, races, and social standings. They carried vials of PTC powder at first, and later a more practical kit that employed paper dipped in PTC solution and dried; volunteers placed the slip of paper on their tongues.

These experiments didn't always go over well. Along the back roads of Depression-era America, rumors circulated that the tests were a eugenics project to sterilize impoverished men. One tester noticed that when he showed up at a farmhouse, the women would gather round while the men made themselves scarce.

The test had its pop culture moment in 1941, when a pair of investigators from the University of Toronto journeyed to a farmhouse in rural Corbeil, Ontario, to test some of the biggest celebrities of the era, the six-year-old Dionne quintuplets.

Born two months prematurely to a farming family, the Dionnes were the first set of identical quintuplets known to have survived infancy. At birth, each could fit in an adult's hand; together, they weighed only thirteen pounds. The quints ignited a global media sensation, becoming symbols of survival for a world suffering through economic calamity. This fame came at a price; Canadian authorities had taken custody of them at four months old, after their father, Oliva, had signed, then canceled, a contract to exhibit the girls at the 1933 World's Fair in Chicago. Authorities feared they might
be exposed to germs, kidnapped, or worse. The government offered a marginally more congenial form of exploitation, imprisoning the quints in a kind of bubble. During their early years, a team of doctors and nurses cared for them at a specially constructed nursery equipped with galleries where tourists could view them. Millions of tourists filed past, casting shadows the girls could see moving eerily across one-way screens.

The Canadian government also made the quints medical subjects for scores of experiments, supervised by the psychology department at the University of Toronto. Their growth and development was obsessively monitored and analyzed. So for UT psychologists Norma Ford and Arnold Mason, testing the quints' tastes was the obvious, inevitable thing to do.

When the time came, Cécile, Yvonne, Émilie, Marie, and Annette were escorted into a room one by one to be tested. Their teacher, Gaetane Vezina, explained what would happen: they'd be given three-quarter-inch strips of paper to place on their tongues, which they would chew. Some would be plain paper, the control, while others would be laced with tastes, including salt, citric acid, saccharine, and bitter quinine.

Since the Dionnes had an identical genetic makeup, it was a surprise when their reactions varied and were subtly impressionistic. Cécile compared the salty paper to the host wafer used in the Catholic Mass, citric acid to cough medicine, saccharine to sweetened medicine, and, for some reason, quinine to maple syrup. These distinctions held until they tasted the PTC paper, where genetics unified their impressions into singular distaste:

Cécile:
“Ce n'est pas bon!” (This is not good!)

Yvonne:
“N'aime pas le goût!” (I don't like the taste!)

Émilie:
“N'aime pas le goût, pas bon!” (I don't like the taste, not good!)

Marie:
“N'aime pas le goût, pas du tout!” (I don't like the taste, not at all!)

Annette:
“Oui, il est fort!” (Yes, that's strong!)

Taste tests for bitterness remain a staple of science. In recent years a chemical called 6-n-propylthiouracil, or PROP, has replaced PTC as the test substance of choice; it lacks PTC's faint odor of sulfur and possible health issues. During a visit to the Monell Chemical Senses Center, I took the test. Danielle Reed, a geneticist and taste researcher, poured a small amount of PROP solution into a paper cup. It was clear, colorless, and odorless. I sipped it. Nothing. Like Arthur Fox, and approximately a quarter of the US population, I was a non-taster. It made sense. I've liked beer, coffee, broccoli, and other bitter things as long as I've been an adult. Non-tasters tend to be insensitive to other flavors, too, one possible explanation for why I like spicy food, and have trouble telling fine wines apart.

Then I took a leap forward into the twenty-first century. My family and I spit into tiny plastic test tubes, sealed them up, and sent them to the genetic testing service 23andMe in Mountain View, California, named for the twenty-three pairs of human chromosomes. The company's genetic profiling technology traces your place in the human family: the continents your ancestors came from, your risk for possible diseases with genetic components, the amount of Neanderthal DNA you carry thanks to ancient inbreeding. The test also reveals which type of Arthur Fox's bitter gene you have. After a few weeks, I got the results from the company website. All of us
were non-tasters. This meant both my wife and I had inherited two copies of a particular non-tasting variant of the gene from our parents, and then passed these on to our kids. (The tests also showed 3 percent of our genome was Neanderthal; about average.) This fit my son's profile, with his penchant for spicy foods. But it seemed to contradict my daughter's preference for bland ones.

Between Fox's time and ours, the human genome—all its genetic material—has been discovered, unspooled, recorded, and partially decoded. Person to person, our genetic code differs on the order of only a tenth of a percent. But that small amount accounts for vast differences in body type, skin color, disease risks—and taste.

In the 1930s no one knew what a taste gene looked like, how it worked, or how the tongue or the brain could distinguish bitter from sweet. There were tantalizing hints about what occurred in these strange domains, but they were nearly impossible to detect with the scientific tools of the time: too small for a microscope, yet larger and more complicated than the chemist's traditional bailiwick of molecular reactions in test tubes. One scientist called it “the world of neglected dimensions.”

By the 1960s, Massachusetts Institute of Technology molecular biologist Martin Rodbell was able to describe the strange biology of taste and genes using the lingo of the then-dawning digital age. Cells, he suggested, respond to their surroundings like a computer handles inputs and outputs. Something called a receptor was in charge of input: it sensed certain things such as bitter molecules, or hormones. Like flipping a switch, this triggered an electrical reaction inside the cell that beamed out a message across the nerves
and to the brain, or another part of the body. Rodbell called this switch the “transducer.” Taste, in other words, could be understood as a simple form of computing. A braised steak, a cup of coffee, a bitter berry—all contain thousands of different substances. Taste receptors—each made by a taste gene—extract essential information out of the chemical chaos of lunch and turn it into a code that the brain can interpret, so it can then react.

The anatomy of taste is a testament to just how wrong the original tongue map was. The average human tongue contains about ten thousand taste buds—tiny structures found on the visible, nub-like papillae. During a meal, the mix of food and drink in the mouth enters a bud via a single, pore-like opening at its tip. A bud is a knotted clump of fifty to eighty specialized cells, each detecting one of the basic tastes. One part of a coiled receptor protein protrudes out of a cell, the other part sits inside. The outside strand grabs molecules floating by, forming a temporary chemical bond. This makes the loops inside the cell pull apart, like the stems at the bottom of a bouquet when the middle is grasped too tight. This signal, essentially flipping the nerve cell to “on,” triggers the cascade of signaling from the tongue to the brain that culminates, a tenth of a second later, in perception, awareness:
Ah, sweet. Ugh, bitter
.

The gene responsible for creating a bitter receptor was discovered, perhaps appropriately, not in a lab but in a computer database. By 1999, the first taste genes and receptors for sweetness, and closely related umami, had recently been isolated, and the scientists responsible had turned their attention to bitterness, performing experiments to isolate receptor cells. Meanwhile, they searched databases of the human genome, which had recently been decoded and published. A
lot of it was still indecipherable strings of As, Cs, Gs, and Ts, the initials for DNA's amino acids. One day, Ken Mueller, a graduate student at a Columbia taste lab, was poring over that hash of letters when he noticed that some strings of code looked awfully like those for the genes of already known receptors: a bit like rhodopsin, which detects light, with a dash of pheromone receptor. It turned out to be code for a bitter receptor. They dubbed it T2R1. Within months, they found sixteen more. The current count is about twenty-three, give or take.

This mother lode explained a lot. There are only three genes for sweet taste, but the sweet receptor's task is simple: find sugars. Nature is filled with so many poisons that a whole repertoire of bitter receptors is needed to detect them. Over hundreds of millions of years, gene replications (like the kind that gave jawless fish and other creatures ever-more-­powerful senses) doubled and quadrupled the array of bitter genes; natural selection tailored each of them to find different kinds of bitter. This is why only a few sugars taste sweet, while the number of bitter-tasting things is uncountable.

T2R1 (now called TAS2R38) turned out to be Arthur Fox's bitter gene. It's a strand of DNA found on chromosome number seven. Small variations in this sequence alter the receptor's chemical makeup and shape, creating the vast differences in people's ability to taste PTC and overall bitter sensitivity.

• • •

Isolating the DNA was, in some sense, the easy part. It was still not clear why nature programmed people with such diverse tastes—why some members of the Bush family loved broccoli while others despised it. There were deeper mysteries
behind the bitter gene. Pursuing them inevitably led scientists back to where it all started: Africa.

At the height of Fox's taste-testing craze in the 1930s, a trio of English scientists became the first to explore the origins of the bitter gene. E. B. Ford, R. A. Fisher, and Julian Huxley were attending the annual International Congress of Genetics in Edinburgh in 1939 when they decided to do a PTC test on man's closest relative, the chimpanzee. They tracked down a Glasgow scientist with a supply of the powder, mixed it into varying concentrations, bottled it up, and set off for the Edinburgh Zoo.

They gave a medicine dropper full of bitter solution to one chimp. She spat it on Fisher. Another, enraged, tried to grab him. Bitter tasters, obviously. Six of the eight chimps were tasters and two were non-tasters, just how a random group of European humans might test. The zoo's orangutans, gorillas, and gibbons had a similar mix. This work was later cut short by World War II, but its implication was fascinating: at some point before humans and chimps diverged millions of years ago, natural selection sorted primordial ape populations into groups of bitter tasters and non-tasters. Whatever advantages these paired traits conferred must have been powerful, because both had persisted for so long.

It was a compelling theory. But once the bitter gene was decoded, it turned out to be dead wrong.

Biologist Stephen Wooding revisited the question in the early 2000s using modern genetic tools. It had recently become possible to track the course of evolution by studying an animal's genome. Over the eons, DNA mutates at a constant rate. Knowing this makes it possible to use differences in the DNA of related species to extrapolate how long ago they diverged from a common ancestor, or when a par
ticular mutation happened. Wooding compared the human DNA code for Fox's bitter-taster gene in a human to that of a chimp. What he saw surprised him: the genes looked nothing alike. Somehow, different DNA codes produced identical taste experiences. Chimps and humans had each evolved the same traits independently, a finding that hinted they were even more potent survival tools than anyone thought.

Scientists have tracked these genetic signals through the past several million years and around the world, looking for what shaped them. Tasting and non-tasting had emerged first in chimpanzees, more than 5 million years ago, and more recently in early humans, between 1.5 million and 500,000 years ago—around the time that older species were starting to give way to the early
Homo sapiens
. Neanderthals, whose species split from a common ancestor with humans about 400,000 years ago, included both tasters and non-tasters, too. Carles Lalueza-Fox of the Evolutionary Biology Institute in Barcelona tested DNA from a 48,000-year-old fossil of a male Neanderthal unearthed, along with ten others, from a cave in El Sidrón, Spain. The Neanderthal turned out to be a taster.

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