Most delicious poison, p.1
Most Delicious Poison, page 1
Copyright © 2023 by Noah Whiteman
Cover design by Julianna Lee
Cover art by Justin Metz
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Illustrations by Julie Johnson
ISBN 978-0-316-38677-7
E3-20230923-JV-NF-ORI
To Shane
Contents
Cover
Title Page
Copyright
Dedication
Introduction
1. Deadly Daisies
2. Forests of Phenolics and Flavonoids
3. Toxic, Titillating, Tumor-Killing Terpenoids
4. Dogbane and Digitalis
5. Hijacked Hormones
6. Abiding Alkaloids
7. Caffeine and Nicotine
8. Devil’s Breath and Silent Death
9. Opioid Overlords
10. The Herbivore’s Dilemma
11. The Spice of Life
12. Nutmeg, Tea, Opium, and Cinchona
13. The Future Pharmacopoeia
Acknowledgments
Discover More
About the Author
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Introduction
A deadly secret lurks within our refrigerators, pantries, medicine cabinets, and gardens. Scratch beneath the surface of a coffee bean, a red pepper flake, a poppy capsule, a Penicillium mold, a foxglove leaf, a magic mushroom, a marijuana bud, a nutmeg seed, or a brewer’s yeast cell, and we find a bevy of poisons.
The chemicals in these products of nature are not a sideshow—they are the main event, and we’ve unwittingly stolen them from a war raging all around us. We use these toxic chemicals to greet our days (caffeine), titillate our tongues (capsaicin), recover from our surgeries (morphine), cure our infections (penicillin), mend our hearts (digoxin), bend our minds (psilocybin), calm our nerves (cannabinol), spice up our food and drink (myristicin), and enhance our social lives (ethanol).
You might be thinking that to call these chemicals poisons or toxins is an exaggeration. After all, at the doses we typically use—a sprinkle, a tablet, a glass—these substances can improve our health and well-being. But at higher doses, as anybody who has ever had a hangover can confirm, these chemicals, whether directly or indirectly, can harm us, too. As sixteenth-century Swiss physician Paracelsus noted, “the dose makes the poison.”
Paracelsus’s maxim is perhaps too general to be useful—and maybe that was his point. It is hard to define a poison or a toxin. That ambiguity is part of the story too (I use the terms poison and toxin interchangeably in this book because their meanings largely overlap). At the wrong dose, even oxygen can be toxic. But there’s a reason we don’t call oxygen a toxin: plants and other organisms with chloroplasts don’t produce oxygen to harm other organisms. The gas is simply a by-product of photosynthesis—the ability to turn carbon dioxide and water into sugar.
The chemicals that I call toxins or poisons, on the other hand, often function as weapons in what Charles Darwin called “the war of nature,” that is, the struggle all organisms endure to survive and reproduce. Some of these struggles are mediated through interactions between organisms, for example, between predator and prey or plant and pollinator. Darwin mused about how these interactions themselves arose through coevolution: “It is interesting to contemplate a tangled bank, clothed with many plants of many kinds, with birds singing on the bushes, with various insects flitting about, and with worms crawling through the damp earth, and to reflect that these elaborately constructed forms, so different from each other, and dependent on each other in so complex a manner, have all been produced by laws acting around us.”
One of the laws Darwin formulated was evolution by natural selection. Natural selection acts on heritable differences between individuals to improve their odds of survival or reproductive output over time. This type of evolution produces new adaptations. Although he focused on traits that he could see with his own eyes, like the varied beaks of the Galápagos finches that now bear his name, we now know that evolution, primarily through coevolution between species, has also generated a profusion of toxic chemicals hidden inside many different organisms. These organisms use the chemicals to gain the upper hand, through offense and defense, in the Darwinian struggle for existence that has played out since life itself began.
This book explores the fascinating and sometimes surprising ways that toxins from nature arose, have been used by us humans and other animals, and have consequently changed the world. We will follow several interrelated threads, or approaches, as we examine how these chemicals have influenced evolution and how they have penetrated each human life, for better and for worse.
One thread concerns the origin stories of the toxins that occur naturally in many organisms. These chemicals, counterintuitively, can help explain why the planet is so filled with life. This is because the war of nature that largely hinges around these chemicals is a dynamo that generates new traits and new species through cycles of defense and counterdefense between ecologically interacting species.
We will trace important similarities between how animals and humans co-opt the same toxins from other organisms and use them as tools of their own to improve their odds of survival and reproduction. This similar behavior reveals that humans, although special in so many ways, are just one of many species that use the chemicals in nature’s pharmacopoeia—and that all creatures depend on this trove of toxins one way or another.
Throughout the book, we will learn how numerous plants and fungi and even some small animals produce copious amounts of toxins that mimic human hormones and neurotransmitters or block their function. On the flip side, you may be surprised to learn that our bodies produce small quantities of some of the strange-sounding chemicals that plants use as defensive shields—such chemicals as aspirin-like molecules and morphine. I will explain the physiology of this process in the human body and show how it can help us understand the human susceptibility to addiction. At the same time, the most promising new treatments for some of these substance use disorders come from the natural pharmacopoeia in the form of psychedelics. A closer look reveals that human use of these psychedelics is not new at all and can be traced to the ancient and ongoing practices of various Indigenous and local peoples across the planet.
Another thread follows medieval Europe’s obsession with nature’s toxins in the form of Asian spices, a hunger that motivated the Age of Exploration. The desire for new sources of spices, and for control of the flow of spices, triggered a geopolitical cataclysm that shaped the past five hundred years of human history and continues to do so today. One consequence, at least in part, is the global biodiversity and climate crisis we face.
As excited as I was to weave all these threads together and tell the story of nature’s toxins, this is not what motivated me to write the book. Instead, the sudden death of my father under tragic circumstances stemming from a substance use disorder in late 2017 is what pushed me to embark on this project.
His long struggle with nature’s toxins came to a head just as my collaborators and I uncovered how the monarch butterfly caterpillar resists the deadly toxins made by the milkweed host plant. Monarchs use these toxins to keep predators like birds at bay as the butterflies migrate thousands of miles from the eastern prairies of Canada and the United States to the subtropical mountains of Mexico. My father, like the butterflies, was using toxins co-opted from other organisms to keep his attackers, both psychological and physiological, at bay, but the toxins were just different ones. His long struggle, the tragic death spiral, and its subsequent impact on me serve as important touchstones throughout the book.
My attempt to grasp why he died allowed me to identify and then draw together the many ways that nature’s toxins affect the world. So, my father’s need for copious amounts of some of nature’s toxins is really another thread, the most personal one, interwoven throughout. You may have had your own similar s truggle or may have loved somebody with a substance use disorder. My hope is that your experience can be your own thread that you will weave throughout the book.
It was my father, who was a naturalist, who first taught me about nature’s toxins. Not only did his knowledge rub off on me, but my growing up in northeastern Minnesota also had some bearing, as did my tendency to use nature as my own escape.
A child’s morbid curiosity about species capable of biting, stinging, scratching, maiming, or poisoning is the bane of parents everywhere. There is always that one neighborhood kid, quiet but tempting fate, and I was that kid. Snakes that bite, toxic newts, snapping turtles, stinky burnet moths, stinging nettles that I couldn’t stop touching (the itch needed to be scratched), and prickly porcupines that maimed our dogs—all these belligerent living things fascinated me. I recall like it was yesterday the confusion in my mother’s eyes when as a kindergartner I presented her with a coffee can filled with a few hundred honeybees I’d collected as they visited the white clover growing in our neighborhood in Duluth, Minnesota.
Although I’d already had a few stings by then, I knew that the bees did so in self-defense. That was just the beginning of my intense curiosity about, and interest in, nature. I would wear garter snakes, which emitted repugnant cloacal secretions, draped around my neck. In Texas, I cupped horned lizards in my hands, enamored by how they could shoot blood from their eyes. In Nevada, I placed venomous black widows in salsa containers to bring home. I didn’t inherit this love of nature and dangerous animals from my mom. My dad is the likely source. At that time, he was a used car salesman, and later, a furniture salesman, but in his heart, he was a naturalist.
When I was ten years old, we moved from Duluth to the Sax-Zim Bog, near the Minnesota townships of Toivola (the Finnish word for “hope”), Elmer, and Meadowlands. What I didn’t know then was that the bog was a birder’s paradise. It often hosts more great gray owls (Strix nebulosa) in the wintertime than does any other place in the continental United States, but few people live there. We moved out there, away from my mom’s family in Duluth, so that my dad could take a better-paying job as manager of a (now closed) furniture store that had become a regional landmark. The store was in a fading farming community that drained the bogs to grow hay for dairy cows. Agriculture was successful in the wet meadows at the edges of the bog for a while, but by the time we got there, the population was aging and steadily declining in size. Most of the children had moved away to greener pastures as adults.
The local school, a single building for kindergarten through twelfth grade, enrolled around 150 students in total, including the 15 in my senior class in 1994. The school was shuttered a few years later. It had been one of ten schools in a district that was about the size of Connecticut and that stretched eighty miles, from Voyageurs National Park on the Ontario border down to the Sax-Zim Bog.
I was a closeted gay teenager and turned my energy toward the beauty of the bog, a few friends, and getting out of there. Nature provided a refuge and spiritual wellspring for me. And it continues to be a wellspring for me, both personally and professionally.
This book will also share insight into how evolutionary biologists like me tackle research questions. In that vein, note that I am only a biologist, not an anthropologist, a chemist, an ethnobotanist, a historian, or a social scientist. Nevertheless, the scope of this book is ambitious, and writing it required that I venture beyond the limits of my main areas of research. The roots of this book extend from my own life, through our recent past as a species, and into events buried by the sands of time, deep in evolutionary history.
Notes, including references used throughout, and an appendix containing further information on the toxins discussed are available online, through a link included at the end of the book.
1.
Deadly Daisies
Within the infant rind of this small flower
Poison hath residence, and medicine power.
—WILLIAM SHAKESPEARE, ROMEO AND JULIET
Rivers, Rings, and Reckonings
I pinned the boutonniere to my lapel, cataloging the species the florist had selected and the corresponding poisons in each. The star of the wintry bouquet was a bright, tiny chrysanthemum (mum) from the daisy family. It was surrounded by some needles of an eastern white pine, clusters of red berries of St. John’s wort, and the spiky blue leaves of sea holly.
I hadn’t requested poisonous plants on my wedding day, but I didn’t have to. All plants produce chemicals that they can deploy as poisons to eliminate the competition, dissuade herbivores, neutralize pathogens, and punish unfaithful pollinators. Plants want to live, as do the many fungi, animals, and other organisms that also use poisons in offense and defense.
Even in its “infant rind,” the mum carried a bevy of toxins, including the terpenoid matricin. The eastern white pine held its own piperidine alkaloids, St. John’s wort contains the phenolic compound hypericin, and sea holly, the aldehyde eryngial.
You probably haven’t heard of these chemicals, but each is also a medicine. Matricin is additionally found in chamomile and yarrow, plants used in traditional healing today and for thousands of years. In the body, matricin breaks down into the beautiful blue chemical chamazulene, which is now being studied for its promise as a pain-relieving drug. The needles of the eastern white pine have long been used by many northeastern Indigenous North American cultures to treat respiratory ailments. The piperidine alkaloids in the needles provide the starting point for the synthesis of opioids like fentanyl. Hypericin in St. John’s wort is widely used to treat depression and other mental health disorders. Finally, Jamaican scientists discovered that the sea holly works as a traditional treatment for roundworm infections through the toxicity of the eryngial.
The big question is why plants would bother making these chemicals in the first place—after all, their synthesis takes up precious energy that could otherwise be put into growing and reproducing. One big hint came in 1964, when the late chemical ecologist Tom Eisner and collaborators published a paper showing that one species of millipedes produces eryngial (also called trans-2-dodecenal), the same chemical produced by the sea holly and other plants, including those in the citrus, ginger, and dill families.
The millipedes secrete eryngial when attacked by assailants like ants and grasshopper mice. The production of this substance in both animals and plants reveals a common pattern in evolution. The same beneficial trait often evolves in many organisms independently—in this case, eryngial as a defense for both animals and plants. The repeated origins of the same trait in different evolutionary lineages is called convergent evolution.
These natural toxins and their sources may sound more familiar than eryngial in millipedes. There is caffeine in coffee beans, cannabinoids in marijuana buds, capsaicin in red pepper flakes, cinnamaldehyde in cinnamon sticks, cocaine in coca leaves, codeine in cough syrup, and cyanide in apple seeds. It may surprise you to learn that many chemicals like these, which we use in food and drink, medicine, spiritual practice, recreation, and even for nefarious purposes like killing, are poisons produced by other organisms that did not evolve with us in mind. Yet these toxins permeate our lives in the most mundane and profound ways.
Such chemicals can be deployed as weapons in the Darwinian war of nature, which was first waged over four billion years ago, when life began. The battles in this chemical war continue to rage all around us, affecting the trajectory of each human life, including my own. Wherever we look, we find these skirmishes. For me, they are the markers of life and of death, the harbingers of joy and pain, and the vehicles of simple pleasures and wild rides.
As I began to write this book in rural Vermont, I also got married to Shane—in the dead of winter and on the solstice. We walked to the edge of the frozen, tea-stained river where Anne, a justice of the peace, awaited. As we trudged through the snow, I recalled a photo of my mother on her wedding day. In it, she holds a bouquet of oxeye daisies and stands on the bank of a blackwater river born in the boreal forest of Minnesota, much like the river Shane and I now stood above.
