Special Episode: Dr. Noah Whiteman & Most Delicious Poison

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the book of the week. Today, we're sinking our teeth into The Most Delicious Poison, the Story of Nature's Toxins From Spices to Vices by doctor Noah Whiteman, who is a professor of genetics, genomics, evolution, and Development at the University of California at Berkeley, as well as the director

of the Esseg Museum of Entomology there. Most Delicious Poison is an engrossing journey through the relationships that humans have formed with animal and plant derived substances, substances that we use to heal, to harm, to self medicate, to hallue, ucinate, to escape, to enhance. Throughout the book, doctor Whiteman expertly weaves stories of these toxins, tracing their evolutionary origins and ecological roles and examining how humans first experimented with them.

I'm sure you've come across the phrase the dose makes the poison, referring to the idea that basically everything has the potential to be toxic. It just depends on how much you consume. So many substances like water, for instance, are toxic and large enough quantities, but don't necessarily possess the dual nature inherent to so many toxins, where they

can act as both medicine as well as poison. Like digitalis derived from foxgloves, is used in important medications that can slow the heart, but can also slow the heart too much i e. Stop the heart i e. Kill someone depending on the dose or opiates derived from opium. Poppy plants are powerful painkillers that revolutionized medicine when first introduced in the form of morphine, but are also powerfully addictive and have led to an enormous and devastating public

health crisis, impacting millions of lives around the world. This catchy phrase provides an opportunity to explore the nature of poisons in more depth, because whether or not something is poisonous depends not just on the dose it's not just the dose that makes the poison, but it's also the recipient. Take milkweed. To monarch butterflies, they're a food source, but to most other animals they're a dangerous snack, leading to nausea, vomiting, diarrhea, lethargy, seizures,

heart rhythm changes, or heart rhythm reduction. How and why is milkweed different for monarch butterflies. We'll get there, but maybe we could add a second principle of toxicology to the dose makes the poison to reflect this variability in how poisons affect us. How about poison is in the

eye of the beholder. We can learn so much about our own humanity and history by exploring our relationships with these plant and animal derived toxins, and doctor Whiteman is here to guide us, and he makes an excellent guide, not just for his expertise on all things toksin related, but also for the personal experiences he shares with his readers. So with that, I think we should just jump into this interview. Thank you so much for joining me today,

doctor Whiteman. I thought your book was absolutely fascinating and so thoughtful, and I really appreciated the way that you wove in your own personal stories and experiences and connected those with the stories of the poisons that you were telling. So the full title of your book is Most Delicious Poison, the Story of Nature's toxins from Spices to Vices, which I love. By the way, great title, But can you tell me a bit more about what that title means, like what makes poisons delicious?

go wrong with Shakespeare. So Most Delicious Poison is from the play Anthony and Cleopatra, And there's a scene in the play where Cleopatra is a opining for Anthony because he's away at war, and she instructs her handmaiden to bring her the mandrake tonic mandra Gora as it was called then, so that she could sleep away Anthony's absence. So she knew that it would allow her to sort of escape her circumstances, her worries, her anxiety, her love, sickness,

and she said bring me my most delicious poison. So Shakespeare knew, you know, as anyone who was alive at that time, presumably in England, knew that certain plants that were growing in the English countryside had the power to do things to one's brain and body that was more than just you know, kind of the usual. And the mandrake was one of them. And so the dual side, the poison, the medicine, you know, the spiritual practice, the poison that use all of us can relate to this.

So this seems to be something universal at least since the time of Shakespeare. And now we know, of course far far you know earlier that to be human, I think, means to do a dance with these chemicals that evolved not really for our purposes, but that we take advantage of for various purposes.

that sort of thing. But he was also had alcohol use disorder. I was going to say he was an alcoholic. That is sort of the old terminology, and now it's referred to as alcohol use disorder, as most drug use disorders are. So those few handfuls of drugs that are commonly associated with different use disorders would be things like opioid use disorder, methamphetamine or emphetamine use disorder, cocaine use disorder,

and a few others marijuana use disorder. And then layered on that is the fact that yeah, so he had was at alcoholic disorder, which was is a progressive disease. So if it's not treated right, so people need more and more alcohol in order to feel normal. And so his use of this chemical to kind of keep his demons away, it turned out, was similar to what I was studying in my lab, even though I didn't plant it that way, and it was only in hindsight that

I realized this. But we were studying interactions between toxic

plants and the animals that eat them. Interestingly, some require eating them in order to complete their life cycle, some insects in particular, So we were studying the monarch butterfly, whose caterpillars feed on toxic milk weed plants in order to complete their development, and they've co evolved with these milk weeds in such a way that the caterpillars actually store the heart poisons that the milk weed plant makes, which are called cardiac glycosides, and they keep those in

their bodies throughout their life, including through metamorphosis and as adults. So they get this dose of poison from the caterpillar stage, you know, when they're feeding a milk weed, and then they carry those poisons in their bodies when they're flying around. And so that's why monarchs are brightly colored. That evolved as a signal to predators, particularly birds, to leave them alone.

So the bird brain selected for those bright colors in the monarch, and large part it wasn't the monarch you know, you know, they're not they didn't evolve that way to make us happy. They're pretty, but they're actually those the colors that they have, which are bright cinnamon, orange, black, and polka dot white, those are warning colors in nature that re evolve over and over and over. And that's because of the animal mind, you know, in large part,

the bird mind and bird brain, I should say. So when he was sort of at the very end of his life, I was, you know, in my lap, pushing these experiments to try to understand the genetic basis for how the monarchs are actually able to resist the these toxins that they store, because most insects are poisoned by these chemicals. And so when we figured that out, which involved the use of crisper, the gene editing technology, and using fruit flies as sort of models to study this

in we're doing very very high tech, intense work. And then my dad succumbed to complications from alcohol use disorder, and so that's when, you know, it was sort of shocking. Even though at some level it was this was going

to happen, the question was exactly how and when. And he had completely estranged himself from our family at that point, which was very sad and stressful, so that when he died it was sort of this big change, you know, in my day to day kind of worry and thinking about what was going on, and that allowed me to have some time to reflect on Wow, really they were

similar things. My dad using alcohol made by yeast, you know, to keep enemies at bay, and sort of my own work in my life, you know, studying a species that was doing something similar to keep its enemies at bait. Just that the enemies are really different. One was sort of choosing to do it, or at least went down that path right, and the other is innate in the case of the monarch, And so the similarities and differences were sort of woven together in my mind, and I

hadn't known it really up until that point. So it was it was an awakening his death I think of reflecting on, you know, human use of chemicals, which I had not studied really except very tangentially in my lap. So that's a long answer, but it's you can see that that it's it's this dance is a little complicated in both cases, but there is this commonality between them.

And the two themes that we regularly that I regularly revisit even in that chapter as you bring up, are the fact that animals self medicate, so that includes things as perhaps Mundane is a sparrow, so they are known to arrested sparas are known to line their nests with sprigs of wormwood artemisia, and scientists have shown that experimentally that that protects the nestlings from natural enemies like ticks and mites and things that would feed on their blood.

That's really interesting, and it just so happens that the study was done in China. The sparrow the species is a rusted sparrow, and the same species of Artemisia is actually put on around door frames and hung from porches at a particular time in China that is associated with this dragon boat festival, and it's meant to sort of ward off you know, evil spirits or whatever, and maybe pests too, you know. So it's like the two things

are mirroring each other. And then one of the other examples I give is chimpanzees in Africa where they're native in central Equatorial Africa, that they use this plant called Vernonia, which is another member of the sunflower family. And what people anthropologists have observed them doing and primatologists have observed them doing, is they will take these it's almost like

a bush like daisy. They'll take the you know, stems of it and then to the bitter pith and then you know, skind of suck out the juices and then throw the stems away. So they're not they're not eating the stems and it doesn't look like they're doing this

for nutrition at all. And one of the reasons is that plant vernonia is used by people to make food but also in medicine, and it's called bitter leaves and it's actually used to make this It's an ingredient in this stew called endo lay, and the bitter leaves are bitter, and so you really have to cook them, you know,

in order to eat them. And so the chimpanzees what the primatologists showed that the vernonia bitter pith chewing is associated with, you know, seasonal variation in worm intestinal worm burdens. So they're doing this bitter pith chewing when worm burdens are high, and that seems to treat them seems to

reduce the impact of the worms and their body. Now, the other mirroring thing is that local people who are living near these chimps, but not just there all over you also use vernonia as a medicine to treat various ailments, including various infectious diseases. So we see this kind of repeated pattern over and over that animals are doing it, we're doing it in our case. It's culturally transmitted information.

That's the big difference, I think, and I'm not saying it's not in chimps, but I don't think we have evidence of that yet if it exists. And then the same patterns are mirrored in other places where great apes occur in nature. In Southeast Asia, orangutans use a tree in the Dressina genus, and so do local people to treat infections. So the orangutans seem to use it for skin infections, and people use it for a variety of things.

And there's a sappin in which is a particular kind of chemical that's been shown to be present in the Dressina juice that may be the active ingredient that is acting pharmacologically. And then maybe the most interesting story is you know some of the and this, I would say is the most difficult to determine if it's really sort of a cause effect thing in terms of why they were doing this. But they're a very close relative of

our species. Homo sapiens, which we call modern humans, is an extinct lineage that was either a subspecies or species or divergent population depending on who you're talking to. But this was what are known as the Neanderthals, Homo neanderthal ensis or Homo sapiens neanderthal ensis, depending on right was it a subspecies or not, And that's sort of a

splitting of hairs thing. But we know that this lineage left Africa before Homo sapiens did and then arrived in Europe and Asia, and you know, it was pretty divergent from humans that were evolving in Africa at the same time, you know, had left sort of butted off and formed a new lineage. And they were in Europe before modern humans were, for example. But eventually modern humans made their way to Europe co existed with the Neanderthals innerbred with them.

So people who are of European descent almost everyone has, you know, somewhere around three percent of the genome is Neanderthal genome, but that species as a whole has gone extinct, and the only vestiges besides the pieces of our DNA many of us that have that are skulls and skeletons

that were left in caves. And so there's a cave in Spain called elc Drone where a number of Neanderthal skeletons have been identified and the genomes of those individuals have been sequenced completely in the case of this one cave, and there's this one Neanderthal in that cave named I call him Sid in the book, just kind of as a way of, you know, kind of keeping track of

what we're talking about. And Sid's was an adult male Neanderthal, and he had an absessed tooth based on his you know, the information that anthropologists got from the cave and the other thing they did this is amazing. He had dental calculus on the back of his teeth, like all of these skeletons did. And what scientists did is they analyzed what was in that calculus and they found remnants of the food that Sid and the other Neanderthals were eating.

And not only that, but they sequenced the DNA of whatever was in the mouth of Sid and his friend, you know, whoever else was in the cave with him who died, they weren't necessarily contemporaneous, and what they found were typical food stuffs that people would expect to Neanderthals already known to be eating at that time in the other mouths. But in Sid's mouth they found something very unique.

They found evidence that Sid had been eating or consuming drinking chemicals that were from yarrow, from this another member of the sunflower family, the astracy, and one of the chemicals is called chemazuline. And you know, yarrow is used as a medicinal by lots of different peoples around the world and has been medicinally important as a plant, and chemazuline is a profin which has sort of a structure

that's very similar to ibuprofen. So it's possible that chemazuline, there's some evidence that it's actually used as an anti it was used as an anti inflammatory, and still is that it has those properties. Okay, So that's one thing. And the infection that Sid had is known because the

DNA of that pathogen was sequenced. When they sequenced the genome of CID which is also amazing, and then microbiome that was in his mouth, and then there was evidence that he was eating bark from a poplar tree, and poplar trees are produce a lot of something called salicilic acid, which is a chemical that is very similar to the chemical that's an aspirin acetyl cl selic acid is just a stylated clicelic acid okay, and salicilic acid on its

own also as anti inflammatory affects, just like actasalicelic acid or aspirin does. They found that in his mouth. Then they also found DNA from penicillium mold, which is the mold that produces the antibiotic penicillin. So none of the

other Neanderthals in the cave had this stuff. And they from the genome sequence, they figured out that sid had some gene variants that allowed him to taste and discern at a very high level bitter chemicals in food and drink, and so some humans also are tasters or not tasters of these bitter compounds. So this is why some people are really sensitive to things like cilantro or mustard greens

and Brussels sprouts and some aren't. Some don't care something it's fine, some hate it, right, And so Sid was a taster. So what this meant was Sid knew what he was doing. He wasn't just eating this stuff because he didn't know what it was. That's the idea anyway, that's inferred by this fact that he had the genetic variance that might allow him to taste really bitter things. So, putting all of this together, the anthropologists have suggested that

Sid was self medicating. And that is old evidence, fifty thousand year old evidence that perhaps our ancestors, our closest relatives, we're doing what we do now that every single person has done right and the home remedies are maybe that's what Sid was using, what his family, his ancestors were doing. So how far back can we go? And that's where the great ape thing becomes interesting, because our closest living relatives,

those great apes, also do it. So then we put all this together, we say, well, this seems to be maybe millions of years old, this practice right in the primate lineage and our specific great ape lineage.

would love to explore more. But as you discuss, there is also tremendous diversity in just the number and kind or types of toxins that plants can produce. Can the type of toxin produced tell us anything about what it's used for or the species that a plant it interacts with.

to repel it or attract it. And you know, a toxin isn't going to attract something necessarily, but a toxin could manipulate the mind of something. And so like a citrus plant will put caffeine that it makes in the nectar to manipulate the minds of bees. And it's not like the plant is thinking. It's not conscious. Plants don't have brains. They're not conscious in the same way we define an animal that has a right. So that's one thing.

It doesn't mean they're not sensing the environment or responding to it, because of course they are all the time, so they have very sophisticated environmental sensing equipment. But they've been selected to do this. That means they've the ones

that do it have been favored to do it. And the mutations that occur in the gene pathway, in the metabolic pathways that are encoded by genes that encode enzymes right that make the metabolism happen, those are the things that have been selected on those random variants that tweak the chemical structures, and the ones that survive better leave more offspring are the ones that pass those traits on

to the next generation. That's Darwinian evolution, right, We know that that is how most of these chemicals arose, and they are making these ornate often very expensive chemicals in terms of energy and also just what's in them. So a lot of them have a nitrogen atom in them, at least one that's expensive because they could be putting that into making pollen or seeds depending on the organism, or spores or eggs in the case of an animal.

Why are they making Why are they doing this? And we know that when you prevent them from doing it by knocking the genes out or you know, the opposite, taking the chemical and sprain it on a plant that doesn't make it, like say caffeine. If you put caffeine on a tomato leaf, they're very well defended from herbivores,

including the ones that can normally attack tomatoes. So all of this evidence you know when you knock them out, when you knock the genes out that make the toxins in plants and you put them out in nature, they don't do very well. They get attacked by insects and other animals. So we know that they serve that function. They protect the plant from being eaten and that allows

them to have more pollen and seeds than they would otherwise. Right, because they have they can protect that tissue that is allowing them to photosynthesize, that's allowing them to make more seeds in pollen. So it's this defense usually that has evolved in the plants against natural enemies, and the natural enemies have been the ones doing the natural selection. They're the selective agents, as we say, so we can only think about it in the context of this kind of

coevolved system. But eventually some animals overcome that and even use the chemicals that the plants are making to their own devices, like the monarch butterfly. So when if we step way back, we can say that many of the plants that are out there, the species that are out there, the diversity of plants, and you know, if we look at their chemicals, they're so diverse among those plants, right,

each one is sort of making a different set. And then yes, there's some similarity among plants that are closer related to each other and the chemicals they make, but there's also diversity that's constantly being born in the chemical structures as time goes on, as evolution proceeds. And then the same is true in the animal side. You know that they're colonizing these plants, they're having to overcome these things and evolve ways of dealing with them and sometimes

even using them. So this chemical dance has produced all of these diverse chemicals over deep time, this co evolutionary dance in the plants and the other organisms that are making them. So that's that's I would say the most important thing to realize is that these chemical this chemical diversity isn't there, you know, because of us. We can benefit from it by tapping into this you know, war of nature, but the chemical diversity itself is there to serve the needs of the makers.

that you mentioned is Humoran and Warfarin and cattle. Do you have a favorite drug origin story.

be using rat poison. But my favorite origin story really is probably curari, which is a concoction. So that's a general term for a concoction that is used as an air poison all over northern South America and the Caribbean. So curari is not just one thing. And these are concoctions that were recipes basically passed down the generations, and they're derived from different plants, mostly in the Amazonian rainforest.

And one of them is called tube kurari and that was simply because the qurrari was stored in bamboo when it was shipped to North America and Europe where it was analyzed. But indigenous peoples were in that case in Ecuador were using tube kurrai as an aero poison for hunting mostly but also in warfare, but mostly in hunting

and blow darts. And the German explorer Alexander von Humboldt in his diary along with Amy Boone Plant his companion, they described their encounter in I think Brazil with an indigenous man who was the man who was making the kirai in that village that he happened to be in, and he was having a conversation with the kurari maker.

But he described the place where he was making it as similar to a pharmacy that you would encounter in Europe with you know, with very sophisticated filters and vessels and you know, lots of very particular ways of doing things. And then the man who was making the karari said

that they called the silent death. You know. His claim was that it was far superior to gunpowder because it was quiet, you know, it was didn't make a sound, and so you could could shoot a prey in the tree with a blow dart and it would hit the animal and then you know, maybe thirty seconds later. Because what became determined was that the chemical in that qurrai was paralyzing the animal. And the animal was still alive when it fell to the ground, but paralyzed, couldn't breathe right,

eventually died. So these concoctions were used all over you know, northern South America and the Amazonian basin and were very valuable. They were traded, they were coveted things, these aero poisons.

But that tube Kurari that was eventually shipped in the twentieth century to be analyzed, and in both Canada and Europe, it was sort of discovered that okay, this tube curari had a compound and alkaloid, that tubocurarin, that became the first muscle relaxant that allowed general anesthesia to proceed in the modern way that we think about during surgery. So it was a stabilized kind of anesthesia that wasn't just ether, right,

which would knock you out. But the problem was if the muscles weren't relaxed during surgery, it made it very dangerous for the patient and very difficult for the surgeon. Right you can imagine why if the muscles are reacting to being cut, that's not a good thing.

one specific one actually had. It played an enormous role in the development of modern medicine and eventually led to the ventilator because if you are paralyzing the skull of muscles during surgery, as anybody knows, you have to be put on a ventilator and have to have artificial respiration, right, So it led to the development of all this technology

that we take for granted now. But it's important to remember that this was really only going in the nineteen forties or so, right, so before that it was this is why surgery is still dangerous, but it was a lot more dangerous then. So that's probably my favorite story.

know yet, Actually we don't know. And the reason that we think this, it's like, yes, it could be the microbiome making it or something, right, but in studies with like mice, you know where they really control well the diet and things like that, they are still making it. So you can even have notobiotic mice, which means mice

that don't have a microbiome, so they're sterile. But the morphine thing, I think is actually more interesting because we have receptors for morphine that are called the endorphin, and the endorphins are these peptides, which means they're they're amino acids that are kind of linked together. Right in chains not super long because they don't fold into proteins, but all proteins are made of these chains of amino acids too, So shorter ones are just called peptides, and endorphins are those.

They're peptides of amino acids, made of amino acids, and they bind to the endorphin receptors. And so say if I had a paper cut in my hand, endorphins would be released, right, so I would initially feel pain, but then the pain gets dulled, and that dulling is in part due to the release of these endorphins. Okay, so they are the pain sort of preventing molecules that allow

us to calm the pain down. And morphine binds to those receptors too, And it was thought that morphine is only found in the opium poppy, and the opium poppy's relatives make similar compounds, but nothing quite gets to morphine except in the opium poppy, and the pathway, the metabolic pathway to make morphine is well characterized in opium poppies, and we roughly know, you know, when the different relatives gained the ability to make the precursors and things like that.

So it's pretty ancient And it turns out this researcher in Saint Louis, this late scientist, discovered some evidence that the brains of mammals and other body parts contained morphine. He could even find it in the urine of some animals. And you know, this was actually older evidence, and people were sort of like, yeah, well, it's just what they're eating,

or you know, they're getting it from the diet. If they're cows, they're probably eating poppies or things like that, or maybe it's the bacteria and their guts making it or transforming some chemical into a morphine like chemical. But he went a step further and actually looked at this in mice. So he had mice that were which are mammals like us, and should do mice make it? Because if we make it, maybe mice make it. Maybe it's something that is more conserved across the tree of life,

you know. And he had these notobiotic mice that didn't have microbiomes. He delivered them via cesarean section so that they're very controlled mice that don't have a microbiome. They have a diet that's very very controlled. And sure enough, those mice in the urine also had morphine. It's like, where, so is this just a byproduct? Like what is going on? How do they do this? People were skeptical still, so he went a step further and had some human cell lines.

The means they're just the cells. They were also notautobiotics, so you know, going to great lengths to make sure there are no bacteria or other microbes living in the culture with them or other cells, and he gave them a very simple precursor that eventually leads to the production of morphine in the opium poppies. So he gave those cells, you know, sort of fe the cells this precursor, and sure enough they make morphine. So it's very clear that human cells. Those were human. I think it was it

was a brain tumor cell line. But this was shocking. I think that that they found morphine was able to be made by these particular cells. And then they proposed that maybe it's in the brain. Maybe maybe it actually is used somehow by the body as a molecule to do the the you know, to make these nervous systems work. But it's still unclear actually what it's doing. We don't know. So that's the bottom line is that it's it's in low amounts, but is it in amounts that are biologically meaningful?

I think that's still a little controversial. Even is it just a waste product of some other metabolic pathway. We don't know, so I think there are many mysteries still. But it's shock. It's shocking, Yes, that I would say with some confidence that you and I made morphine today. It is.

two parter. Sorry, but can we predict whether a newly discovered toxin would be addictive or psychedelic or what effects it's likely to have just based on its structure?

you know, what are they? Where are they binding? So I think that part is not completely understood in terms of being able to predict, but we could we can

get close. Like fentanyl was sort of you know, this pipuriodine structure that forms the basis of it that was used sort of because Jansen discovered that, you know, morphine has at its base this piperiodine ring too, you know, so could he exploit that and make a synthetic version that was sort of had properties that were made it advantageous to use, And yes it did, but it also had the problem of being really really really potent, and

so fentanyl is just the latest way in the opioid crisis, right. But going back to your question about addiction, well, I think the first thing to say is I'm not an addiction specialist, so that's one thing. But if you take something like alcohol use disorder and compare it to opioid use disorder, there are similarities and differences in the neural circuits involved. The same is true for something like methamphetamine

use disorder. But what they have in common is, you know, very often it's either that sort of dopamine or opioid endogenous opioid in other words, endorphin based systems that are involved. Not always, but they're they're usually involved, right, So there's some some problem with those two pathways, usually in the

brains of people who become addicted to things. So that's one of the things that I think most addiction specialists would agree that the people who are most prone to developing the use disorders, whether it's alcohol use disorder, opioid use disorder, something like methamphetamine use disorder, are people who come from childhoods where there was adverse events, abuse, or neglect, or all three trauma of some kind. So this book, this Gobbor mates book. It's in the Realm of Something Ghosts.

I can't remember the full title, but it's a great book because he talks about this. He sort of breaks it down into the systems that get set in place as infants through early childhood. Right, These dopamine systems, the opioid system the systems that are allowing our bodies and brains to work properly, to respond to stimuli properly. But they need feedback, They need interaction with the people around

us in order to develop properly. They need that kind of stimulation, right, They need to feel we need to feel safe in order to properly develop. And when that goes, when that's out of whack, then there becomes the need for external you know, sort of external stimulation or damping down of those pathways. So it's a really rough way of describing it, but I would say that people begin to use these drugs, they take them, like most people who take prescription opioids do not become do not develop

opid use disorders. Right, So why do the people who develop them develop them? What do they have in common? And one of the things they have many of them have in common, are these early childhood issues with their environment, and so they're sort of set on a trajectory where they're open to developing these use disorders very easily. And

that's also true for alcohol use disorder. So there's a genetic component too though, so we know that in some cases, yes, if you have certain opiid receptor variants, you are more prone to developing a use disorder. You may be more prone to developing alcohol use disorder and an opioid use disorder. So that's interesting too, and there's some debate about that as well, like does it crossover, which kind of gets

at your question. But the psychedelic thing is interesting because psychedelics, broadly speaking, are just those chemicals that are binding primarily in terms of how we think about a psychedelic to a set of serotonin receptors in the brain, a subset of them, and they are not addictive in that in the ways that you and I have been talking about.

So there's no use disorder known that really is going to come from a psychedelic experience, so you don't people don't get addicted to them in that kind of same sense, And what addiction is is sort of like, you know, how do we define that most people would define it as you know, using a chemical in this case in a way that causes us harm or we want to stop, but can't you know? So that there's the inability to stop using something and the continued use of it is

causing problems in other areas of our life. Now you could say I'm a addicted to caffeine. Is that a problem? No? Does it cause problems in my other parts of my life? No? It enhances other parts of my life. So is that an addiction? And I think that's why the word use disorder is better than addiction because it right it sort of, it narrows it down a little bit more as a problem because it's affecting your other aspects of your life, whether it's your health or your well being.

French press or drink unfiltered coffee in large quantities ever. Again, and the reason is, it's a long story, but to boil it down, so to speak, it was actually boiled Scandinavian coffee, which is unfiltered. It's a way that coffee was traditionally made in Scandinavia, including Finland. And an initial set of epidemiological studies came out that were strange. They were showing that, particularly for men, there was a higher risk of cardiovascular disease and risk of death among people

who drank coffee. Now this was strange because we know from huge, much larger and much more recent epidemiological studies that drinking coffee is protective at in terms of reducing death risk. Like that that is the case, and we don't know in terms of cause and effect or exactly what's going on. But you know, a lot more is

known now than was known then. These early studies, which were done in the middle part of the twentieth century where people were still drinking boiled coffee and Scandinavia, triggered some interest in what was causing that potentially instead of just like life factors that were associated with people who drank coffee, right, So they wanted to know, is there something in this coffee that is causing higher risk of heart attack basically, and if they picked it up in

the study, it was scatatistically significant. So it wasn't just like a little thing. It wasn't just a little blip in the data. It was concerning enough where they invested a lot of money in trying to figure out and time what was going on. And so in countries kind of all over they started digging into this and what they found was a set of chemical that are in coffee beans that are they have this name capistol and coweol, and they are a group of terpenoids. They're dieterping alcohols.

That's the technical kind of class that they're in. And these are fat soluble very lightweight molecules that like being dissolved in things like lipids. And what they do is it turns out that that those two chemicals were probably the reason that they detected this higher cardiovascular risk in people who are drinking unfiltered coffee basically. And what they do is these two chemicals they are not themselves cholesterol.

So you know, it's not like you're eating cheese or you know, you got to watch your diet because of that, because, right, our shrimp have a lot of cholesterol. No, the LDLC, which is the cholesterol that's kind of known as the bad cholesterol, although that's also a little bit of a misnumber, right, but the LDLC cholesterol is the cholesterol level that doctors are tracking, whether in when they decide to give you

a statin or not. Okay, so this is the stuff that is forming plaques, that's causing athlosclerosis and that sort of thing. You know, The idea is that lower is better in terms of you know, life extension. So what they noticed was cafaestell and kawi alf. You if I gave that to you, just the same amount that you would get in say, drinking four cups of French press coffee your cholesterol levels if you hadn't been drinking French press,

so I couldn't do this to you. But if you hadn't been drinking French press, you could measure the increase and you would see an increase of maybe ten to fifteen percent of the LDLC in the weeks two weeks after, you know, continuing to drink it. And so they did that. You know, they isolated these compounds. It's definitely them that's causing it, and they're filtered out by a paper filter. They're also filtered out by the formation of what's called

a filter cake of the grounds of coffee themselves. Because these diterping alcohols caffistan call wee all bind to small particles in the coffee that you during the grind process, right, that are made during the grind process, and then during

the brewing process. If there's not something to catch those small particles, those small particles will make it through into the brew, which of course they do in a French press because that thing you plunge through is just a really rough mesh filter, right, So it's catching some of the grounds, but you know, a lot most of the smallest particles are making the way through, which means most of the available caffistan call we all is also making

it through, and the amount that's available depends on the bean. Robust and Arabica have different amounts of the caffistan callwe all. How much it's roasted has an effect, Okay, But roughly speaking, if you have an Arabica bean, it's going to have a decent amount of caffistan caullwie al in it, and if you don't filter it, you're gonna raise your cholesterol because of it. At least that's how I interpret it.

All this littera and I did a deep dive, and the nutrition literature is fascinating because there are these studies where what they got to do with the graduate students was make coffee six ways from Sunday and then measure the kaffistall colwieol in it. It's just so funny. But what's clear is that an auto drip, because it's water gently kind of dripping down on the grounds, it's kind

of retaining the structure of all of those grounds. Right, even though the gold mesh filter absolutely would let the diet tirping alcohols through the little poor and the mesh, right, but what's trapping them is that all of the coffee grounds themselves. And so that's why a gold mesh filter will work to filter out most of the caffistan callie all in an auto drip, but not a pore over because you're swirling the grounds around in the poor over,

aren't you right? You're taking that kettle and moving them around, swirling them around, so the particles will get through the gold mesh and a pour over, but not a paper filter. So this is like I cannot believe, this is where I ended up in the book, like a lot of attention, but you know, I like going down these rabbit holes. And if you think about cholesterol levels, you know, the two most potent inducing chemicals in our diet for LDL

cholesterol are these two chemicals. And the way they work is they bind to a receptor in your body that tricks your liver into making more LDL cholesterol. That is what happens. So really stepping back, thinking like if there's one public health message, you know, and I can't give it because I'm not an epidemiologist or a physician, but for myself, just for my own health, you know, this was the most salient thing and I stopped drinking French

press too, and I used to only drink it. And of course LDL cholesterol levels vary a lot between people for lots of reasons, including genetics and diet. Right, not in the broadest sense, but for me, I thought, this is a simple thing I could do just to keep it down. It really depends on the person, you know, Like, I don't want to make an or arching statement about this, but the literature is clear. The scientific literature is clear

about this. In my mind, it has been muddied and not well communicated, is what I would say.

the middle part of the twentieth century. This ecologist did sort of a transect, you know, sort of measuring alkaloid levels across different biomes from the poles to the equator, and then they had these controls in equatorial zones that had mountains, so there's less diversity at the tops of the mountains right than at the base and lowland tropical forests, and so that kind of mimics the latitudinal gradient that von Humboldt discovered. This mirroring by the way, in terms

of species numbers and how diverse things get. They're more diverse at the equator and less diverse at the poles, more diverse in lowland tropical forests than at the upper limits of the mountains. And they saw the alkaloid diversity parallel that so plants on average produce more alkaloid diversity than in the tropics and the lowland tropics than they do at the tops of the mountains per species, and

also towards the poles. And so the interpretation was that the interactions between species are stronger in the tropics and where there's more diversity, where it's warmer for a longer

period of time or stable warmth basically. And so these cradles of biodiversity that harbor most species also harbor most of the toxins, most of the chemical diversity that we have on the planet that have access to now and in the future, and so and those lands are largely controlled by indigenous people, who are also the most endangered you know, cultures in the world in terms of their just their being right and their languages, their cultures, all

of that, they're the least empowered. And so the other thing that's interesting, just as a general rule, not just in the tropics, but indigenous lands hold maybe fifty percent of the carbon sequestering capacity of the terrestrial realm. And so I didn't think I'd end up here, but it was sort of like forget about the pharmacopeia, just thinking about, you know, the future of the planet is really in

the hands of indigenous people and empowering them. And if we do that, so many things get solved, Like their existence is fortify right, their rights are guaranteed, and then the rest kind of hitches along for the ride, is what I would say. So human rights kind of becomes like the focus of the book at the end, but you know, it's sort of like, yeah, the other stuff is sort of just tagging along. But you know, the future pharmacopeia for our descendants is going to be there

in the tropics. Yes they're drugs. New drugs will come out of the temperate zones too, but most of them are going to come out of the tropics still, you know, for natural drugs, and yes, synthetic drugs with AI and all, this definitely very promising. You know, directed evolution, there's all kinds of new ways of thinking about making synthetic drugs

and that's going to be very important. But on the other hand, if you just look at the approved cancer drugs anti cancer drugs, more than half are from plants, so that that's still true, and so there's untapped potential. People's lives have been saved by tax all I guarantee you of some of your listeners. So this really hits home for people when you think about that, right, think about the next tax all that is somewhere in the Atlantic forest in Brazil and some tree that exists in

a tiny population, is it going to be there? You know? And that's the thing. It's like, this is this is something that we can control that we have the we have right. The fate is in our hands.

to doctor Whiteman's lab website. And don't forget you can check out our website for all sorts of other cool things, including but not limited to, transcripts, quarantine and Placibrita, recipes, show notes and references for all of our episodes, links to merch our bookshop dot Org, affiliate account, our Goodreads list, a first hand account, form, and music by Bloodmobile. Speaking of which, thank you to Bloodmobile for providing the music

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