Tricking The Tongue: How Biotechnology Might Let Us Cut Sugar And Salt, But Keep The Taste

Taste Manipulation: CGI For Your Mouth?

In “The Matrix,” the machines that rule the Earth have locked humanity in a total immersion experience that fools all five senses, including taste. Digital information fed to millions of captive brains makes people think they’re eating steak or cereal instead of nutrient goop.

In our more mundane, human-dominated world, taste remains a tricky thing to manipulate. Scientists in Singapore recently unveiled a device to create virtual “tastes” using a little electrode placed on the tip of your tongue. Electrical and thermal stimulation fools your taste buds into registering salty, sweet, sour or bitter flavors. The researchers see their invention as a way for diabetics to enjoy sweetness without affecting their blood-sugar levels, or to enhance the quality of life for cancer patients and other people with dysfunctional tastes. Commercial applications abound as well, especially in the gaming industry; imagine getting a hit of virtual lemon candy or chocolate after completing a level on Candy Crush.

But manipulating your taste buds isn’t something just for people who want to make video games or enable diabetic folks to enjoy sweet flavors. In fact, some of the biggest food companies in the world are having a go at it – with the aim of shaping the future of nutrition and maybe making a pile of money in the process.

Altering tastes could also be the large-scale, corporate version of Jessica Seinfeld’s “hide spinach in the brownies” strategy. Americans aren’t eating right on their own, so perhaps tricking them into eating a less junky kind of junk food might be the easiest solution. Could altering tastes also be a boon to public health? Not everyone’s eating up the message.

“Promises, promises,” New York University nutrition professor Marion Nestle wrote in an email. “The biotech industry is always talking about promises. I’m wondering when these companies will get around to fulfilling them. Until they do, this is all talk.”

Hacking Taste Buds For Fun And Profit (But Mostly Profit)

The holy grail of processed food would be a soda that tastes just as sweet as a regular Coke or Pepsi, but with a fraction of the sugar. If companies can find new ways to sweeten their drinks without adding calories – or artificial sweeteners, they may be able to remove high fructose corn syrup (HFCS), which has a public image about as favorable as Congress (even though HFCS is probably no worse than regular sugar).

The situation is pretty ripe for a new contender in the taste game. Americans are growing more wary of existing diet soda options; while aspartame and other artificial sweeteners have been dubbed safe again and again by regulators, many worry about unseen consequences. This past July, Purdue University researcher Susan Swithers opined [PDF] that sugar substitutes could still pose a risk for weight gain, diabetes and heart disease, and possibly induce “metabolic derangements.” Sales of diet sodas are down 7 percent over the past year, while sales of regular soda have fallen just 2 percent over the same period, according to Time.

In their quest to find the low-calorie Holy Grail, some companies are pursuing new super-sweeteners like stevia, the South American herb that can be used as a zero-calorie sweetener (which has enjoyed a higher profile as a key character’s sweetener of choice on the popular series “Breaking Bad.”) Just this week, Coca-Cola CEO Muthar Kent hinted that its stevia-sweetened Coca-Cola Life, already a hit in Argentina, could start arriving on shelves in America next year.

But there may be more than one road to the zero-calorie, sweet-as-sugar Grail. Scientists have a pretty good understanding of how our taste receptors work – particularly a certain class of taste receptors responsible for detecting sweet, bitter, and savoryflavors. When the right food ingredient binds to these little molecular receivers, it kicks off a signaling pathway through the nerves and up to our brains. Knowing the details of the molecular machinery that translates the sugar molecule into a sweet sensation in the tongue and brain is the first step in hacking it.

Senomyx, a biotechnology firm based in San Diego, Calif., is developing a compound code-named S617. The company doesn’t give much detail about how S617 works, but says it’s a “taste modifier” that gives your tongue a heightened sense of sweetness from a smaller amount of sugar.

Taste tests with S617 showed that you could subtract a lot of HFCS and sugar from foods and beverages but keep a sweet taste, Senomyx CEO Kent Snyder said in an August 2012 statement. More importantly, a little bit of S617 goes a long way. The taste modifier’s effectiveness at very low concentrations is an attractive prospect for companies watching the bottom line.

Senomyx has collaborations in place with many of the biggest players in the food industry, including Nestle and Japanese seasonings maker Ajinomoto. But PepsiCo is Senomyx’s sweetest deal, generating $17.7 million in revenues in 2012 alone – 56 percent of the company’s total revenues. The four-year deal was struck in 2010, and expires next August.

But how does this particular ingredient bump up sweetness? Representatives from Senomyx declined to comment specifically on S617, saying it was “too early” to discuss since the additive has not yet received regulatory approval.

One already widely known example of a taste-modifying substance is miraculin, found in the berries of Synsepalum dulcificum, also known as “miracle fruit.” Miraculin is not sweet by itself, but has a curious effect on the palate: for up to an hour after you take it, it will change sour tastes to sweet.

Miraculin was nixed as an artificial sweetener by the FDA in the 1970s, but has found a second life as a party novelty. Miracle fruit parties (or, as the New York Times dubbed them, "flavor-tripping parties") have been around for decades, since miraculin became available in pill form. You get your friends together and pop a miraculin pill or an actual miracle fruit berry; then you all go to town on a smorgasboard of sour foods, savoring the tasty transformation. Lemons become like candy; tabasco sauce tastes like hot doughnut glaze. Wash it down with a delectable swig of vinegar.

For awhile, scientists weren’t sure just how miraculin works. One researcher speculated to a Wired reporter in 2006 that miraculin may slightly distort the shape of the sweet receptors on the tongue, making them receptive to acidic molecules as well. But it seems that it’s actually miracle fruit itself that’s the shapeshifter. In 2011, a group of researchers found that miraculin’s molecular structure changes in the presence of sour-tasting acids, resulting in a shape that binds strongly to the sweet receptor – not just unlocking the door to taste, but propping it open.

However S617 might work, Senomyx’s taste modifying ingredient could start cropping up in your drinks and food as soon as next year. In a November press release, the company says that it is on-track to submit what’s called a GRAS filing for S617 to the U.S. Food and Drug Administration in the first quarter of 2014. GRAS stands for Generally Recognized as Safe, and is a quicker path to market for food additives that does not require premarket approval by the FDA.

For a substance to meet this safety criteria, “the scientific data and information about the use of a substance must be widely known and there must be a consensus among qualified experts that those data and information establish that the substance is safe under the conditions of its intended use,” FDA spokesperson Theresa Eisenman wrote in an email.

The other option is a Food Additive Petition, where the FDA takes more time to evaluate the properties of the substance and determine that the ingredient is safe for consumption.

Senomyx’s Snyder expects that S617 will be introduced into a wide range of foods and beverages starting in 2014, according to a November statement. Partner PepsiCo is, of course, known for its sodas, but it sells a lot of other popular beverages as well: ready-to-drink coffee products from Starbucks, Gatorade, and Tropicana juices. PepsiCo Americas Foods’ portfolio includes Frito-Lay North America (selling chips like Doritos, Cheetos, and Lay’s) Quaker Foods North America (Quaker Oatmeal and Cap’n Crunch cereals) and Gamesa, one of the largest cookie-makers in Mexico.

Senomyx already has several sweetener modifiers heading towards the market that pump up the sweetness of table sugar or the artificial sweetener sucralose (more familiar as Splenda). One sugar taste modifier, Sweetmyx SR96, is the first product Senomyx plans to sell directly to the flavor industry. Flavor companies would then use Sweetmyx SR96 to create flavors for their beverage company customers, which would be marketed as flavor-restoring ingredients for reduced sugar drinks.

Sweetness isn’t the only taste that Senomyx is hacking. The company is working on new savory flavors – including an ingredient that can mimic MSG, as well as compounds to block bitter tastes, and “cooling agents” (think the icy taste you get from wintergreen-flavored gum).

Taste modification is still a pretty open field, but one that’s heating up quickly. In its quarterly report filed in November, Senomyx noted that many companies and universities are researching taste receptors and are filing patents. One of those competitors is Brunswick, N.J.-based Chromocell, which In December 2010 signed a collaboration agreement with chief PepsiCo rival Coca-Cola. (Senomyx had also worked with Coca-Cola before on an eight-year contract, but that collaboration yielded no commercial products, according to CBS).

Chromocell is also working with food giant Nestle to look for ingredients that mimic the taste of salt. Hilary Green, a spokesperson for Nestle, said the research was at too early of a stage to predict when the fruits of the collaboration might be seasoning its products.

“Independently of our collaboration with Chromocell, Nestlé is working on understanding the biology of taste,” Green wrote in an email. “One aspect of our research concerns how the visual appeal of food affects taste.”

Nestle’s researchers showed people pictures of either high-calorie foods (like pizza or pastries) or low-calorie foods (like string beans or watermelon) right before zapping their tongues to produce an unfamiliar neutral taste, using an electrode. They found that people liked the new taste much more if they were looking at pictures of high-calorie foods than pictures of low-calorie foods, even though the taste stimulus was the same in both occasions.

Could this, then, be the future of food: a soda sweetened with metabolically invisible ingredients, to wash down a salad, cloaked with a holographic pizza? A little dystopian, maybe, but possibly healthier?

Fooling the Tongue, But Maybe Not the Brain?

Even if we succeed in keeping foods sweet with taste modifiers, there’s the chance we might still long for a sugar rush somewhere in our heads. Research conducted with artificial sweeteners has found that replicating a pleasant taste may not be enough to throw the reward switch in our brains that keeps us chasing the sugar-spangled dragon.

In one study published in the journal NeuroImage in 2008, a team of researchers led by Guido Frank of the University of Colorado recruited 12 women to try drinks sweetened either with sugar (sucrose) or artificial sweetener (sucralose). The researchers asked the women to rate the drinks, and also scanned their brains with MRI machines. While the subjects could taste sweetness from both drinks, only sugar caused areas of the midbrain connected to reward pathways to light up on the scanner.

“Thus, brain response distinguishes the caloric from the non-caloric sweetener, although the conscious mind could not,” Frank and colleagues wrote. “This could have important implications on how effective artificial sweeteners are in their ability to substitute sugar intake.”

But then again, maybe our brains will simply adjust to the new sensations. San Diego State University researchers Erin Green and Claire Murphy scanned the brains of both habitual diet soda drinkers and people without a diet soda habit. They reported in the journal Physiology and Behavior that the reward processing regions in the brains of the diet soda addicts reacted almost identically to water spiked with sugar and water laced with the artificial sweetener saccharin.

So, however you sweeten your soda, your brains may adapt to match your tastes.

Bumps on the Road

But the nature of processed food is very closely intertwined with the ingredients that companies are now trying to cut back on. It might not be quite as simple as just bumping up the flavor of food, according to New York Times reporter Michael Moss, the author of “Salt Sugar Fat: How the Food Giants Hooked Us.” Food companies, he says, are between a rock and a hard place because salt and sugars aren’t in there just for flavor.

These ingredients are “acting as preservatives so the food can stay on the shelves for weeks or months at a time and they're there to avoid the use of more costly ingredients like fresh herbs and spices,” Moss said in an interview with the radio program The Splendid Table earlier this year.

Both sugar and salt can act as preservatives through the same principle: drying food out. A high concentration of sugar or salt absorbs water from food, but also draws water out of any old cell that happens to be around, including a bacterium. The sugary or salty environment inside your soda or your bag of chips is an inhospitable world for bacteria. Dialing back on certain additives might make food healthier, but possibly also more welcoming to microbes.

Even if foods with taste modifying products turn out to be safe, effective, and palatable, unexpected problems can arise. As GMOs have proven, mixing food and technology requires some public relations finesse. Senomyx has already experienced a taste of this trouble; a couple of years ago, pro-life groups got up in arms about the company’s use of human-derived cells in its flavor research. Senomyx is not sprinkling bits of aborted fetus in your soda, but the company’s basic research has involved transplanting taste receptors onto some human cells derived from a kidney taken from an aborted fetus back in the Netherlands in the late 1970s.

Because of its reputation as a reliable cell line, HEK 293 cells are widely used in vaccine and drug development. In gene therapy research, HEK 293 cells are often used to create adenoviruses, which are used to deliver modified genes to test subjects. A group of Canadian researchers said in 2010 that HEK 293 cells could be a cost-effective way of producing lots of influenza virus to use in flu vaccines – a process that’s currently performed inside fertilized chicken eggs or insect cells.

These HEK 293 cells, as they’re known to scientists, are “very easy to work with and have become workhorses of cellular biology,” Matthew Herper explained at Forbes in 2012.

Physician Alvin Wong delved into the ethics of HEK 293 cells from a conservative Christian perspective in a paper [PDF] for the National Catholic Bioethics Quarterly (spoiler alert: neither Wong nor the Vatican are fans of using the cells). Whether the history of the cell line will give consumers pause remains to be seen.

Still, the true test for taste modifiers on the market will likely be relatively simple: will people like it? Scientists and companies have been making sugar substitutes for decades, but problems have arisen with every one: bitter aftertastes, cancer scares, in the case of saccharin (later proven to be safe ). Given the option of aspartame, Splenda, or stevia, most people will still reach for the sugar bowl. Taste is a funny and complex thing, as Monell Center taste researcher Paul Breslin told the New York Times:

“If you give them something that’s sweet but different, they innately know [it’s] different.”