“Most Delicious Poison”: An Interview With Author Noah Whiteman 

In his book Most Delicious Poison: The Story of Nature’s Toxins–from Spices to Vices, Professor Noah Whiteman asserts we’re late to the dance, but fully immersed. Questioned by Lavender, he recently discussed our timing at greater length.

LAVENDER: Eons before animals and green plants, fungi and yeasts–sentient, if not “intelligent”–used elements for sustenance, procreation, and defense, drawing from the same toolbox latecomer Homo saps dubbed “Periodic Table,” while rifling its 94 natural elements for personal use–and misuse. Straightforward? Simple? You offer a more radical take on “simplicity.”  

NOAH WHITEMAN: The story of “the greatest show on Earth” is the origin of life and its diversification that led to us and all the beautiful creatures with whom we share the planet.

From the age of the rock where the first bona fide microbial fossil bacteria were found (in what is now Australia), Earthly life began 3.5 billion years ago. Some 575 million years ago, the first ocean animals evolved, leaving pancake-like fossils. From these early animals descended several invertebrate branches, creeping, crawling onto land 400 million years ago–70 million years after the first land plants evolved from algae.

Our ancestors and those of insects were borne from water to land where two lineages colonized independently. The first land vertebrates (our ancestors) were predators, while land invertebrates likely fed on detritus, algae, early plants, and associated fungi. Insects evolved from crustaceans and took advantage of the land plants’ rapid diversification plants to use them for food and habitat.

Today, roughly 50% of all insect species are herbivorous, pressuring plants to continually evolve new defenses against them. Plant modular body-plans allow some regrowth; they can afford to be eaten–to a degree–but they’re “sitting ducks” that cannot flee. Plants that created chemical defenses that activated upon insect attack were favored, developing an arms race with insects. Other animals eat plants as well–small mites to large elephants, and they, also, are at war with plants.

LAVENDER: What constitutes “Poison,” and what “Delicious”?

WHITEMAN: Paracelsus’s maxim stated: “It is the dose that makes the poison.” Anything can be poisonous, although the verb “to poison” implies an agent, acting with intent. Arsenic can be used as a poison, but it didn’t appear on the planet because it happens to be toxic, while caffeine can be thought of as a poison because it’s used in six different plant lineages as a chemical defense.”

LAVENDER: You’re an evolutionary botanist, not, you stress, an anthropologist, chemist, ethnobotanist, or social scientist. What does your niche bring to the mix?

WHITEMAN: I have training in genetics, evolutionary biology, insect biology, plant biology, ornithology, ecology, and botany, so one can see why I would study the evolution of plant-animal relationships where the plants make chemicals for protection while the animals create countermeasures to eat the plants safely. Some animals, like the monarch butterfly, use toxins in their own defense.

I went to a small liberal arts college in Minnesota run by compassionate, deeply intellectual Benedictine monks and nuns; there I learned the importance of art and the humanities to the ability to more fully understand the human condition. The humanistic arc of the book reflects my training.

LAVENDER: What birthed the poisons/toxins? When? How obvious is  it that none originally evolved to benefit Homo saps?

WHITEMAN: Random mutations in the genomes of these organisms allowed for the evolution of new chemicals formed by the enzymes tweaked by the mutations.

Sometimes, a copy of a gene encoding an enzyme is made twice, allowing one of the genes to explore a new role, and, as mutations hit, can even create a new chemical substrate.

If this mutated version provides an advantage, say by making caffeine from a methylxanthine precursor, it’s selected.

The agent then doing the natural selection is an herbivore because plants that now make caffeine will be resistant to insect attack. We know this because if you artificially insert that pathway into a plant that doesn’t normally make it, that plant will be protected.

But nature finds a way; eventually some insects overcome the chemical defense, like the coffee berry borer beetle!

The age of humans goes back 150,000 to 200,000 years, while the plant chemicals we rely on first evolved tens to hundreds of millions of years ago; we know this from DNA sequences and the molecular clock (that rate at which mutations occur and accumulate in populations over time.) That isn’t to say we don’t manipulate these chemicals now–we do–but they first evolved without any humans around, even before Great Apes.

LAVENDER: Would you briefly illustrate one of the complex chemical give-and-takes you describe between human diseases?

WHITEMAN: Human culture is co-evolving with our genes and with the infectious disease agents that attack us. The plants we eat can sometimes synergize our own defenses against these enemies; one of the best examples is favism, the most common inherited enzyme deficiency in humans (G6PD deficiency) that causes red blood cells to be sensitive to some dietary toxins.

Fava beans contain a set of toxins called vicine alkaloids that cannot be tolerated by folks with G6PD deficiency–if consumed, their red blood cells die.

But guess what has to invade red blood cells to reproduce? Malarial parasites. Interestingly, where favism is most common is also where people eat a lot of fava and broad beans.

The hypothesis is that the bean-gene combo synergizes resistance to malaria. People with favism are more resistant to malaria, even if the favism is also harmful. A similar connection exists between sickle cell trait, cassava consumption, and malaria.

LAVENDER: Most Delicious Poison was inspired by your father’s personal struggles with AUD (alcohol use disorder.) Would you share something about him and his story’s thread throughout the book–and Monarch caterpillars?

WHITEMAN: He was a naturalist and used both nature and alcohol to cope with his demons. I was exposed to two sides; the generous, patient naturalist who showed me the wonders of the natural world, and the dumbed-down drunken man who slurred his words at night. The Jekyll-and-Hyde dipoles were confusing then, but I understand them now. He was using nature’s toxins to ward off his own enemies just as many of the animals I study–like the monarch butterfly– do as well.

LAVENDER: What most pressing questions concerning toxins are yet to be answered? Are any mind-altering-chemical experiments promising relief for AUD and similar disorders?

WHITEMAN: The big question is whether and to what extent psychedelic molecules can serve as therapeutics for folks suffering from use disorders and other mental health challenges. There is tremendous promise, but much is unknown and there’s a lot of hype.

I’m convinced these drugs are potentially transformative when combined with behavioral, cognitive and other therapies.

My colleague at Cal, Professor Gül Dolen has shown that these drugs open up something in our brains called “the critical period” that may hold the secret to the drugs seemingly curative powers.

At the same time, we must have double-blind, placebo-controlled clinical trials if we are going to really understand whether and to what extent these drugs do work to break use-disorder, depression, PTSD and other mental health disorders.

AI is also providing a new capacity to design drugs not created by nature or to tweak drugs that did evolve first in nature to make them more effective at treating new diseases. A recent paper used AI to design new antibiotics that may well become a new class of these important drugs.

LAVENDER: And Julie Johnson’s engaging and informative illustrations?

WHITEMAN: Julie Johnson was a true creative partner in the book. A picture is worth a thousand words and Julie hit the mark, illustrating interactions between species, the beautiful structures of chemicals, often adding historical context.

Whiteman is Professor of Integrative Biology and of Molecular and Cell Biology at University of California, Berkeley. He lives in Oakland with husband Collin Pine, author of children’s book The Garden Next Door  (see”Books” pxx)