Most Delicious Poison: The Story of Nature's Toxins—From Spices to Vices

by Noah Whiteman

Neanderthals also probably shared our ability to taste bitter chemicals. People vary in their like or dislike of certain bitter plants such as broccoli and brussels sprouts. This difference is in part determined by the genetic variants a person carries for a gene called TAS2R38, which is expressed in our taste buds. The common form of this gene allows people to taste bitter chemicals like phenylthiocarbamide (PTC), which has long been used by scientists to screen individuals for bitter detection. Those of us carrying at least one copy of this common TAS2R38 gene variant, which is dominant, are called PTC tasters. Those of us carrying two copies of the less common form of TAS2R38, which is recessive, are called PTC nontasters.

I later learned that it was Harvey Firestone, the tire magnate, who had brought the tree from India and given it to Edison in the hopes that its milky latex would soon provide a domestic source of natural rubber on the US mainland. Edison analyzed more than seventeen thousand latex-producing species for their potential as sources of natural rubber. The research was funded in part by Firestone and Henry Ford, both of whom were troubled by the rubber monopolies held by the British and Dutch in the early twentieth century. The inventor found that more than a thousand of these species produced measurable rubber in their latex. Edison died six years after receiving the tree. Around the same time, synthetic rubber from petroleum was invented to augment the supply. Still, natural rubber remained a $1.6 billion industry in 2021, and nearly all of it is produced in Southeast Asia.

Shane and I heard a tremendous crash early one morning in the spring of 2017 as a torrential winter storm hit Berkeley. I looked out our south-facing window and saw nothing unusual. Apparently, I was looking in the wrong direction. A few minutes later, I heard a knock at the door. It was my neighbor, who looked upset. She had just returned from dropping her daughter off at school and informed us that a tree had fallen in the parking lot behind our apartment. I followed her along the sidewalk to find the trunk of a massive blue gum, a species of eucalyptus tree, at least a hundred feet tall and ten feet in diameter, on top of my car. The firefighters and I laughed in disbelief as we walked single file on top of the massive trunk to inspect the remains of my Volkswagen Golf below, which had been split in half and completely crushed. The smell of terpenoids from biodiesel (this was Berkeley, after all) and eucalyptol burned our throats. I would have been killed instantly if I had been in the car when the tree fell. Although it was an act of God, I couldn’t help but think it was a sign, given that I study the natural enemies of plants. Curious about why a forest of Australian eucalyptus trees was thriving in the East Bay hills, I dug into the biology of these blue gums. The answer is uninteresting; they were planted for lumber and as windbreaks. In my search for answers, I discovered that they have a devious side beyond their car-crushing potential.

When I was around twelve, he had begun morphing from a gentle outdoorsman into an angry, paranoid, and gun-obsessed man. First it was Rush Limbaugh’s voice on his car radio, and then my father would parrot how the government was taking his money and giving it to people who didn’t work. Then it was the Guns & Ammo magazine subscription, the National Rifle Association membership, and the shotgun placed under my bed, just in case “we” needed it. Eventually, a target was set up in the yard so he could unload into it bullets from his newly acquired SKS Chinese assault rifle on his days off and after work.

I was convinced enough by what I gleaned from the scientific literature to change my habits. I stopped my twenty-year practice of using a French press to make coffee. Although I occasionally splurge on an espresso drink (which has only modest levels of the terpenoids) when I’m out and about or traveling, at home I now only make filtered coffee using the automatic drip machine with a gold mesh filter. Or I make pour-over coffee using a paper filter—and an unbleached one at that.

To figure out what is really going on, the researchers found that the TAS2R genetic variant associated with higher sensitivity to caffeine was more strongly associated with increased intake of caffeinated than decaffeinated coffee. This association explained, biologically, the findings about higher bitter sensitivity being related to higher coffee intake from the survey. The conclusion—that those of us with heightened sensitivity to the bitter taste of caffeine learn to associate it with psychostimulatory reward—is a remarkable and counterintuitive finding.

In 2004, scientists reported a new opium poppy mutant produced through plant breeding methods. Called top1, short for thebaine oripavine poppy 1, the genetically engineered plant accumulates thebaine and the morphine precursor oripavine but not morphine itself. Since morphine is not required to produce hydrocodone and oxycodone—only thebaine is needed—top1 poppies represented an opportunity for pharmaceutical companies. That’s because separating thebaine from morphine in opium poppies is difficult, and with top1 poppies, pharmaceutical companies didn’t need to do this separation step. As a bonus, top1 poppies would not be useful to the illicit drug trade, because heroin is made from morphine, not thebaine. The poppy mutant was a win-win, except for the millions of people who wound up addicted to the plentiful opioids derived from top1 poppies.

In laboratory experiments, fruit flies tend to avoid solutions laced with morphine as much as they do caffeine. If these insects take another sip despite the bitter taste, an even greater aversion to morphine develops over the course of an experiment. If mammals return to take another taste, by contrast, a preference for diet laced with morphine can develop. Rats preferred food laced with bitter morphine over food laced with bitter quinine. And just like humans, other mammals, like rats, that are socially isolated or are under other stresses are prone to increase their preferences for, and dose of, morphine. This initial aversion followed by reinforcement is called the paradox of drug reward.

One evening, when I was around five years old, I asked my dad if I could try a taste of his beer. He agreed, but only if I took a tiny sip. The ethanol in the beer burned my mouth and throat. But I also noticed the bitter taste. The bitterness came from the phenolic humulone (alpha-lupulic acid) from hops, the flowers of the hop plant. Lips curled, brow furrowed, I asked, “Why do you like that?” He replied, “It’s an acquired taste.” It was anathema to me.

As any cat or dog owner knows, Glendinning’s findings support the fact that dogs and cats can be poisoned by many plants and fungi that pose no real problem for omnivorous humans or herbivorous pets like rabbits. For example, grapes, raisins, and tamarinds contain high levels of tartaric acid, which can cause acute kidney failure in dogs when ingested. Another well-known example is from plants in the genus Allium, including chives, garlic, leeks, onions, ramps, and shallots. Such plants are highly toxic to both cats and dogs owing to disulfides, which cause anemia, partly by reducing the activity of G6PD in a process similar to what occurs in favism. These same plants, however, are not toxic to humans, hamsters, rabbits, or horses—all omnivores or herbivores. You may be wondering how these comparisons across animals and their relationships with nature’s toxins apply to us. When we instead compare bitter thresholds and detoxification repertoires across the developmental stages of our own species, a remarkably parallel set of patterns emerges with those Glendinning found across mammal species with different diets. Before we do that, we need to briefly retrace our own evolutionary history.

Now I find myself doing the same thing I found so inexplicable then. I am not alone. You may also seek out a bit of the nose-stinging, eye-watering, tongue-tingling, skin-flushing isothiocyanates in mustard condiments like wasabi and the sharp, throat-clenching piperidine alkaloids in cracked black pepper. Plants in the mustard family Brassicaceae are far more than just a spicy condiment. They are staple crops, including arugula, broccoli, brussels sprouts, cabbages, canola or rapeseed, cauliflower, collard greens, daikon, gai lan, horseradish, kale, kohlrabi, mizuna, mustard seeds, peppergrass, radishes, rapini, romanesco, rutabaga, turnips, wasabi, watercress, and winter cress. Close relatives in the same lineage that produce mustard oils include capers, meadowfoam, moringa, papaya, and nasturtium. Toxic mustard oil defenses could be one reason why these plants are so successful: worldwide, there are over five thousand species that have the ability to make mustard oils.

Because these toxins are also poisonous to the plants that make them, they are formed only when the plant has been wounded. The way this works is that protoxins called glucosinolates are stored in the plant’s cells like bombs with unlit fuses in a bunker. Mustard plants also produce glucosidase enzymes, which are stored in different cells. These enzymes are like a box of matches. When glucosinolate and glucosidase come into contact as an herbivore begins to munch away, the fuse is lit and the bomb explodes, transforming the glucosinolate into the toxic mustard oil. This is why it takes a bit of chewing before your fresh arugula, daikon, or watercress begins to taste spicy, hot, or, as some describe it, peppery.

When mustard vegetables are cooked, however, the heat disables the plant’s glucosidase enzymes. For this reason, cooking is sort of like pouring water on the matches. The glucosinolates then move into our digestive tracts without forming mustard oils—not yet, anyway. Our gut bacteria have plans for the glucosinolates. After the gut bacteria turn the glucosinolates into mustard oils, the toxins are then broken down further into an amine and hydrogen sulfide gas. The bacteria use the amines as nutrients, but the sulfur-smelling gas bubbles are waste that find their way out of the other end of our digestive tract. Think of your microbiome and your gut itself as your personal kimchi fermenter.

Yet, once the GSH and GST enzyme levels become elevated thanks to sulforaphane, the higher levels of GSH and GST enzymes scavenge other toxins, including those produced through normal metabolism. This indirect benefit of sulforaphane consumption, this GSH and GST enzyme boost, is the main way that sulforaphane slows progression of Parkinson’s disease-like symptoms in lab animals. I know this was a lot of detail, but the triggering of our body’s detoxification response by some dietary toxins like mustard oils illustrates an important concept as it relates not only to spices but also to other toxins we ingest. Hormesis, which comes from the Greek word hormē, “to set in motion,” is a poorly understood but widely observed phenomenon. Through this phenomenon, modest amounts of environmental stressors, like cold shock (ice bath plunge), heat shock (sauna), or spicy mustard oils, can protect us from cellular damage caused by both internal and external stressors that our bodies will encounter in the near future. The idea is that mild environmental stressors can trigger an adaptive physiological response that soon dampens the negative effect of the stressor. The concept of hormesis is controversial because the underlying mechanisms driving it may be quite different, depending on the stressor, and their later downstream effects may or may not matter for our health and well-being. The long-term cost-to-benefit ratio of hormesis as a prophylaxis or treatment for illnesses is quite unc...

Several of their findings may explain in an ultimate, evolutionary sense why we use spices. First, spices prevent spoilage, a major cause of bacterially mediated food poisoning. Indeed, nearly all of the spices called for in these recipes and used at the levels commonly found in food inhibit bacterial growth. The spices most effective at killing bacteria were also more likely to be used across all countries. Intriguingly, in recipes that include spices containing chemicals degradable by heat, like the chemicals in parsley and cilantro, the spices were added after cooking and not before. Those that did not degrade in heat were added during cooking.

Second, spices are more heavily relied on in the tropics than in the higher, cooler latitudes.

Although internal strife associated with the White Lotus Rebellion and widespread corruption had weakened the Chinese Empire internally even before the opening battle of the Opium War, historians agree that the cheap opium flowing in from British-controlled India contributed to its decline. One perspective is that the British Empire’s rapacious desire for economic gain and hegemony led to the downfall of the most advanced civilizations the world had known.

The origin of our modern pharmacopoeia cannot be understood without an appreciation of the dynamic land use practices of Indigenous and local people who have lived in these ecosystems for millennia. In all the tropical biomes of the world, humans have been present and augmenting the landscape for hundreds to tens of thousands of years. The Mayan ruins, for example, rising from what is now dense jungle in Mexico give testament to this long heritage of cultivation. So do the eleven recently discovered 1,500-year-old human settlements under a rain forest in the Bolivian Amazon. The notion that these regions are pristine, or untouched by human influence, is inaccurate and rooted in the same tropes that motivated colonial and imperial conquest for centuries. Today’s primary tropical rain forest may have been a village at some distant point in the past. To varying degrees, tropical ecosystems have felt the impact of humans for as long as humans have been living in them. The most diverse ecosystems are not prehistoric time capsules.