Cracking the Science of Smell
Bloomberg Businessweek|August 23, 2021
A new generation of companies is homing in on one of the hardest problems in tech: Replicating human scent
By Zach Schonbrun

Osh Agabi’s solution to one of biotechnology’s thorniest problems looks like an iridescent purple nipple the size of a steering wheel. Other than that, it’s inconspicuous. It doesn’t beep or pulse or hum. Hanging from a wall, it just sits quietly and smells.

Airports, arenas, factories, people—they all stink, and they stink in particular ways. We know this because our noses tell us so. But attempts to re-create our oldest sensory experience with machines and technology have been woefully lacking. Modern everyday devices might be smart enough to recognize our faces and voices, read our pulses, and track our emotions, but they can’t smell. The best example of a commercial device that can reliably pick up chemical signals in the air hasn’t changed in years. It’s called a smoke detector.

But Koniku Inc., which Agabi founded in 2015, says it’s landed upon a sensory breakthrough. In July the company struck an agreement with the world’s biggest brewer, Anheuser-Busch InBev SA/NV, to deploy the Konikore, as the purple bubble is called, to measure how a beverage’s aromatic notes are perceived and experienced by the nose, with the aim of enhancing flavor. And in the next few weeks, the Konikore is expected to start showing up in some U.S. airport terminals, thanks to a partnership with Airbus SE that’s geared toward bomb de tection. Koniku has also signed a development deal with electronic sensor =manufacturer Thermo Fisher Scientific Inc. to create a method for detecting traces of marijuana on people suspected of driving under the influence.

“What the camera did for vision, we’re now doing for smell,” Agabi says. “I believe we are the first company to build a small camera on the smell sidewalk.” The difference with Koniku’s “camera” is that the purple encasement contains tiny living nerve cells. They’re suspended inside a proprietary solution designed to replicate the mucosa, the layer of membrane high up in our nasal cavities. The cells contain specific transmembrane proteins programmed to recognize odor molecules, precisely as those in our nose would catch a whiff. The reaction triggers a cascade of signaling events, eventually leading to a chip reader that interprets which receptors were triggered. And there you have it: the authentic recognition of an odor.

Koniku is one of at least three startups attempting to bring their biotechnological achievements in odor detection out of the laboratory. Together they’re racing for investors, customers, and regulatory approval. One of them, Aromyx Corp., in Mountain View, Calif., has been testing how its own receptor-based platform reacts in the presence of a variety of diseases, including pancreatic cancer, prostate cancer, and malaria. And that got started before a viral pandemic forced the world to reconsider what could be wafting around us in the air. Aromyx’s vision is to reduce the size of the instrument that underlies the technology of its lab-based system to the size of a pregnancy test, capable of telling you that you have cancer or Covid-19 (or, better yet, nothing). In addition to Aromyx and Koniku, there’s Aryballe, a French startup that’s attracted backing from Samsung Electronics Co. and Hyundai Motor Co. for its handheld sensor, the NeOse Advance. Aryballe’s device contains peptides, or fragments of proteins, that operate in gas rather than liquid like the Konikore.

For Avery Gilbert and other veteran smell scientists, the battle for smell-sensor supremacy is reminiscent of the late 1990s and early 2000s, when advancements in olfactory research brought about a flurry of electronic devices with catchy names—AromaScan, the Cyranose, ScenTrak. None lived up to their hype and became anything close to a universal odor reader. Gilbert says a biological sniffing system has the potential to do much more. “My feeling is it’s got to be way more efficient,” he says. “You’re using what mammalian noses are using. It’s much closer to what we’re smelling and wanting to smell.”

“Why has it always been so difficult to solve olfaction?” Agabi asks. “The physics that rely on it are quite hard. Vision, comparatively, is an easy problem. When people see something, you have these photons that interact with sensors that convert that energy. Pretty straightforward, because these are energy particles by definition. Sound is compression of air—an energetic particle. But the smell is a different beast.”

Compared with what we know about vision and hearing, our understanding of the olfactory process, whether the inhalation of a molecule or the perception of an odor, remains in the Dark Ages. Here’s what we do know: About 400 receptor types in our noses capture ambient molecules bobbing about in the air. These molecules trigger a complex chain reaction ultimately transforming into a perception, a signal. The signal pinballs its way around our brains: a coffee, dark roast; Christmas morning; Mom’s kitchen.

Our nasal receptors are capable of discriminating billions, if not trillions, of smells, particularly ones that act as flavor components for food or drink. The newest smell technology tries to mimic this by drawing on an array of disciplines, from neuroscience and organic chemistry to machine learning, data science—and, more recently, epidemiology. For obvious reasons, scent-based disease detection has gotten a fresh look over the past year. To some, the dream of a device that can blend into the background and monitor someone’s breath or sweat for illness has never been closer to reality. Then again, if smell technology has been consistent about one thing over the years, it’s a failure to deliver on its promises.

When I first spoke to Josh Silverman, the chief executive officer of Aromyx, it was in January 2020. Reports about a mysterious virus in China were beginning to circulate. Silverman’s company was focused primarily on using its platform to help flavorists discern which aromas were activating certain receptors, in an effort to enhance the taste of, say, plant-based meat or an artificially sweetened beverage.

The system had also been used to analyze urine samples of prostate cancer patients since 2019. When Covid became a worldwide pandemic, the potential for Aromyx to produce a touch-free diagnostic tool became the company’s new raison d’être. “I’ve seen the reports saying that dogs are being used in airports to ‘smell’ the virus on travelers,” Silverman says. “That’s not really possible. What they’re smelling is the molecular byproducts that have been altered by the virus and get diffused as sweat. Our scent platform can detect those changes the same way.”

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