WEBVTT - Special Episode: Dr. Noah Whiteman & Most Delicious Poison 0:00:44.080 --> 0:00:47.720 Hi, I'm Aaron Welsh and this is This Podcast Will 0:00:47.760 --> 0:00:51.479 Kill You. Welcome back to another of our tp w 0:00:51.760 --> 0:00:55.120 k Y book Club episodes, where we get to interview 0:00:55.160 --> 0:01:00.280 authors about their amazing books covering wide ranging topics insideience 0:01:00.320 --> 0:01:04.679 in medicine, and when I say wide ranging, I really 0:01:04.760 --> 0:01:05.960 mean wide ranging. 0:01:06.480 --> 0:01:07.600 So far, we've. 0:01:07.440 --> 0:01:12.679 Gotten into uncovering the origins of American gynecology and exploring 0:01:12.760 --> 0:01:15.600 what can happen when a single molecule in our brain 0:01:15.760 --> 0:01:19.360 goes awry, and we've got so much more that we're 0:01:19.400 --> 0:01:23.760 going to cover this season, like misogyny at MIT, the 0:01:23.800 --> 0:01:28.399 fraught future of Phosphorus, the post COVID pandemic Playbook, and 0:01:28.800 --> 0:01:31.639 so much more. 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One last 0:02:09.040 --> 0:02:11.600 thing before we get into the topic of today's episode, 0:02:11.919 --> 0:02:15.000 and that is a simple request from the Errands to 0:02:15.120 --> 0:02:20.040 our listeners. If you're enjoying the podcast, let us know, rate, review, 0:02:20.160 --> 0:02:25.160 and subscribe. It really helps us out. Okay, finally, onto 0:02:25.200 --> 0:02:28.240 the book of the week. Today, we're sinking our teeth 0:02:28.360 --> 0:02:32.919 into The Most Delicious Poison, the Story of Nature's Toxins 0:02:32.919 --> 0:02:36.560 From Spices to Vices by doctor Noah Whiteman, who is 0:02:36.600 --> 0:02:40.480 a professor of genetics, genomics, evolution, and Development at the 0:02:40.560 --> 0:02:43.880 University of California at Berkeley, as well as the director 0:02:43.960 --> 0:02:48.160 of the Esseg Museum of Entomology there. Most Delicious Poison 0:02:48.400 --> 0:02:51.880 is an engrossing journey through the relationships that humans have 0:02:52.000 --> 0:02:56.160 formed with animal and plant derived substances, substances that we 0:02:56.320 --> 0:03:00.480 use to heal, to harm, to self medicate, to hallue, ucinate, 0:03:00.919 --> 0:03:05.840 to escape, to enhance. Throughout the book, doctor Whiteman expertly 0:03:05.840 --> 0:03:10.400 weaves stories of these toxins, tracing their evolutionary origins and 0:03:10.480 --> 0:03:15.000 ecological roles and examining how humans first experimented with them. 0:03:15.800 --> 0:03:18.440 I'm sure you've come across the phrase the dose makes 0:03:18.440 --> 0:03:22.280 the poison, referring to the idea that basically everything has 0:03:22.320 --> 0:03:24.720 the potential to be toxic. It just depends on how 0:03:24.760 --> 0:03:29.359 much you consume. So many substances like water, for instance, 0:03:29.760 --> 0:03:34.040 are toxic and large enough quantities, but don't necessarily possess 0:03:34.120 --> 0:03:37.840 the dual nature inherent to so many toxins, where they 0:03:37.840 --> 0:03:41.640 can act as both medicine as well as poison. Like 0:03:41.720 --> 0:03:46.360 digitalis derived from foxgloves, is used in important medications that 0:03:46.400 --> 0:03:49.440 can slow the heart, but can also slow the heart 0:03:49.520 --> 0:03:52.839 too much i e. Stop the heart i e. Kill 0:03:52.880 --> 0:03:57.560 someone depending on the dose or opiates derived from opium. 0:03:57.600 --> 0:04:03.240 Poppy plants are powerful painkillers that revolutionized medicine when first 0:04:03.280 --> 0:04:07.160 introduced in the form of morphine, but are also powerfully 0:04:07.200 --> 0:04:11.000 addictive and have led to an enormous and devastating public 0:04:11.040 --> 0:04:15.760 health crisis, impacting millions of lives around the world. This 0:04:15.880 --> 0:04:19.279 catchy phrase provides an opportunity to explore the nature of 0:04:19.360 --> 0:04:23.039 poisons in more depth, because whether or not something is 0:04:23.120 --> 0:04:26.760 poisonous depends not just on the dose it's not just 0:04:26.880 --> 0:04:30.400 the dose that makes the poison, but it's also the recipient. 0:04:30.880 --> 0:04:35.000 Take milkweed. To monarch butterflies, they're a food source, but 0:04:35.160 --> 0:04:42.280 to most other animals they're a dangerous snack, leading to nausea, vomiting, diarrhea, lethargy, seizures, 0:04:42.320 --> 0:04:46.800 heart rhythm changes, or heart rhythm reduction. How and why 0:04:46.920 --> 0:04:50.839 is milkweed different for monarch butterflies. We'll get there, but 0:04:51.000 --> 0:04:54.120 maybe we could add a second principle of toxicology to 0:04:54.480 --> 0:04:57.880 the dose makes the poison to reflect this variability in 0:04:57.960 --> 0:05:02.159 how poisons affect us. How about poison is in the 0:05:02.160 --> 0:05:06.159 eye of the beholder. We can learn so much about 0:05:06.160 --> 0:05:10.240 our own humanity and history by exploring our relationships with 0:05:10.440 --> 0:05:14.599 these plant and animal derived toxins, and doctor Whiteman is 0:05:14.640 --> 0:05:18.120 here to guide us, and he makes an excellent guide, 0:05:18.240 --> 0:05:21.640 not just for his expertise on all things toksin related, 0:05:22.040 --> 0:05:25.320 but also for the personal experiences he shares with his readers. 0:05:26.000 --> 0:05:28.720 So with that, I think we should just jump into 0:05:28.720 --> 0:05:56.040 this interview. Thank you so much for joining me today, 0:05:56.080 --> 0:06:00.240 doctor Whiteman. I thought your book was absolutely fascinating and 0:06:00.320 --> 0:06:03.640 so thoughtful, and I really appreciated the way that you 0:06:03.880 --> 0:06:08.360 wove in your own personal stories and experiences and connected 0:06:08.440 --> 0:06:11.680 those with the stories of the poisons that you were telling. 0:06:12.800 --> 0:06:16.880 So the full title of your book is Most Delicious Poison, 0:06:17.160 --> 0:06:21.000 the Story of Nature's toxins from Spices to Vices, which 0:06:21.080 --> 0:06:24.160 I love. By the way, great title, But can you 0:06:24.240 --> 0:06:27.520 tell me a bit more about what that title means, 0:06:27.960 --> 0:06:30.640 like what makes poisons delicious? 0:06:31.160 --> 0:06:33.440 Sure? Well, first of all, Aeron, thank you for having 0:06:33.440 --> 0:06:37.360 me on your podcast, which the title of which I love. 0:06:37.760 --> 0:06:40.720 This podcast will kill you because my book is a 0:06:40.760 --> 0:06:45.400 little bit about that. The title of the book is 0:06:45.520 --> 0:06:49.000 really the first part is from Shakespeare, and one can't 0:06:49.000 --> 0:06:52.800 go wrong with Shakespeare. So Most Delicious Poison is from 0:06:52.839 --> 0:06:57.760 the play Anthony and Cleopatra, And there's a scene in 0:06:57.800 --> 0:07:02.440 the play where Cleopatra is a opining for Anthony because 0:07:02.440 --> 0:07:05.719 he's away at war, and she instructs her handmaiden to 0:07:05.720 --> 0:07:09.680 bring her the mandrake tonic mandra Gora as it was 0:07:09.720 --> 0:07:14.120 called then, so that she could sleep away Anthony's absence. 0:07:14.200 --> 0:07:17.720 So she knew that it would allow her to sort 0:07:17.720 --> 0:07:21.760 of escape her circumstances, her worries, her anxiety, her love, sickness, 0:07:22.520 --> 0:07:26.880 and she said bring me my most delicious poison. So 0:07:27.080 --> 0:07:31.000 Shakespeare knew, you know, as anyone who was alive at 0:07:31.000 --> 0:07:36.560 that time, presumably in England, knew that certain plants that 0:07:36.600 --> 0:07:41.440 were growing in the English countryside had the power to 0:07:41.520 --> 0:07:44.600 do things to one's brain and body that was more 0:07:44.680 --> 0:07:48.640 than just you know, kind of the usual. And the 0:07:48.680 --> 0:07:52.880 mandrake was one of them. And so the dual side, 0:07:53.320 --> 0:07:57.840 the poison, the medicine, you know, the spiritual practice, the 0:07:57.880 --> 0:08:02.760 poison that use all of us can relate to this. 0:08:03.000 --> 0:08:07.120 So this seems to be something universal at least since 0:08:07.120 --> 0:08:08.960 the time of Shakespeare. And now we know, of course 0:08:09.120 --> 0:08:14.200 far far you know earlier that to be human, I think, 0:08:14.360 --> 0:08:19.120 means to do a dance with these chemicals that evolved 0:08:19.160 --> 0:08:22.920 not really for our purposes, but that we take advantage 0:08:22.960 --> 0:08:24.800 of for various purposes. 0:08:25.120 --> 0:08:29.840 Yeah, yeah, follow that thread of curiosity, for better or 0:08:29.880 --> 0:08:32.400 sometimes worse, I guess, depending on the dose. 0:08:33.480 --> 0:08:37.280 Right, So the delicious poison part illustrates the duality that 0:08:37.360 --> 0:08:39.200 is inherent I think in all of it. And it's 0:08:39.240 --> 0:08:41.360 sort of going back to the dose makes the poison, 0:08:41.480 --> 0:08:46.240 as you know, the Paracelsus is maxim But yeah, so 0:08:46.640 --> 0:08:50.880 I thought, well, it's hard to beat Shakespeare. So borrowing 0:08:51.440 --> 0:08:55.600 you know three words from him, you know did does 0:08:55.720 --> 0:08:57.480 encapsulate I think what the book is about. 0:08:58.559 --> 0:09:01.080 Let's take a quick break, will be back before you 0:09:01.160 --> 0:09:20.920 know it. Welcome back, everyone, I'm here chatting with doctor 0:09:21.000 --> 0:09:25.000 Noel Whiteman about his book Most Dangerous Poison. Let's jump 0:09:25.080 --> 0:09:28.520 back into some questions. So you mentioned in the book 0:09:28.679 --> 0:09:31.360 that you were motivated to write this book after the 0:09:31.400 --> 0:09:35.120 death of your father. How did this book take shape 0:09:35.160 --> 0:09:38.520 and how did his life and death influence the threads 0:09:38.520 --> 0:09:39.880 that you followed while writing. 0:09:41.040 --> 0:09:43.480 My dad was a naturalist, as I talked about in 0:09:43.520 --> 0:09:45.280 the book, and I think my kind of love of 0:09:45.400 --> 0:09:48.160 nature and wanting to be ensconced in it, wanting to 0:09:48.240 --> 0:09:54.640 understand it was definitely enhanced by him and his own 0:09:55.160 --> 0:09:59.760 abilities and interests. As all children do, they mimic their parents, 0:10:00.480 --> 0:10:02.920 they take advantage of what their parents know, and I 0:10:02.960 --> 0:10:06.600 certainly did that. And it was a way that he 0:10:06.640 --> 0:10:09.319 spent time with my brother and I when we were 0:10:09.400 --> 0:10:12.960 kids as well on the weekends and on vacation and 0:10:12.960 --> 0:10:16.040 that sort of thing. But he was also had alcohol 0:10:16.080 --> 0:10:18.560 use disorder. I was going to say he was an alcoholic. 0:10:18.600 --> 0:10:23.280 That is sort of the old terminology, and now it's 0:10:23.360 --> 0:10:27.760 referred to as alcohol use disorder, as most drug use 0:10:27.880 --> 0:10:33.120 disorders are. So those few handfuls of drugs that are 0:10:33.360 --> 0:10:35.880 commonly associated with different use disorders would be things like 0:10:35.960 --> 0:10:41.480 opioid use disorder, methamphetamine or emphetamine use disorder, cocaine use disorder, 0:10:42.000 --> 0:10:46.880 and a few others marijuana use disorder. And then layered 0:10:46.920 --> 0:10:51.280 on that is the fact that yeah, so he had 0:10:51.480 --> 0:10:56.280 was at alcoholic disorder, which was is a progressive disease. 0:10:56.400 --> 0:10:59.360 So if it's not treated right, so people need more 0:10:59.400 --> 0:11:04.439 and more alcohol in order to feel normal. And so 0:11:04.559 --> 0:11:06.959 his use of this chemical to kind of keep his 0:11:07.040 --> 0:11:10.560 demons away, it turned out, was similar to what I 0:11:10.600 --> 0:11:12.720 was studying in my lab, even though I didn't plant 0:11:12.760 --> 0:11:15.160 it that way, and it was only in hindsight that 0:11:15.200 --> 0:11:20.079 I realized this. But we were studying interactions between toxic 0:11:20.120 --> 0:11:24.800 plants and the animals that eat them. Interestingly, some require 0:11:24.880 --> 0:11:26.880 eating them in order to complete their life cycle, some 0:11:27.160 --> 0:11:30.679 insects in particular, So we were studying the monarch butterfly, 0:11:31.000 --> 0:11:34.600 whose caterpillars feed on toxic milk weed plants in order 0:11:34.720 --> 0:11:38.520 to complete their development, and they've co evolved with these 0:11:38.559 --> 0:11:42.400 milk weeds in such a way that the caterpillars actually 0:11:42.679 --> 0:11:45.720 store the heart poisons that the milk weed plant makes, 0:11:45.760 --> 0:11:49.800 which are called cardiac glycosides, and they keep those in 0:11:49.840 --> 0:11:54.840 their bodies throughout their life, including through metamorphosis and as adults. 0:11:55.240 --> 0:11:58.600 So they get this dose of poison from the caterpillar stage, 0:11:58.760 --> 0:12:00.880 you know, when they're feeding a milk weed, and then 0:12:00.920 --> 0:12:04.040 they carry those poisons in their bodies when they're flying around. 0:12:04.080 --> 0:12:08.160 And so that's why monarchs are brightly colored. That evolved 0:12:08.480 --> 0:12:12.800 as a signal to predators, particularly birds, to leave them alone. 0:12:12.840 --> 0:12:16.679 So the bird brain selected for those bright colors in 0:12:16.720 --> 0:12:19.280 the monarch, and large part it wasn't the monarch you know, 0:12:19.920 --> 0:12:21.960 you know, they're not they didn't evolve that way to 0:12:22.000 --> 0:12:25.440 make us happy. They're pretty, but they're actually those the 0:12:25.440 --> 0:12:29.320 colors that they have, which are bright cinnamon, orange, black, 0:12:29.760 --> 0:12:33.640 and polka dot white, those are warning colors in nature 0:12:33.679 --> 0:12:36.240 that re evolve over and over and over. And that's 0:12:36.280 --> 0:12:40.480 because of the animal mind, you know, in large part, 0:12:40.520 --> 0:12:45.400 the bird mind and bird brain, I should say. So 0:12:46.600 --> 0:12:49.200 when he was sort of at the very end of 0:12:49.240 --> 0:12:53.120 his life, I was, you know, in my lap, pushing 0:12:53.120 --> 0:12:57.200 these experiments to try to understand the genetic basis for 0:12:57.440 --> 0:13:00.199 how the monarchs are actually able to resist the these 0:13:00.240 --> 0:13:03.360 toxins that they store, because most insects are poisoned by 0:13:03.400 --> 0:13:06.920 these chemicals. And so when we figured that out, which 0:13:06.920 --> 0:13:09.520 involved the use of crisper, the gene editing technology, and 0:13:09.640 --> 0:13:12.920 using fruit flies as sort of models to study this 0:13:13.040 --> 0:13:17.160 in we're doing very very high tech, intense work. And 0:13:17.200 --> 0:13:21.280 then my dad succumbed to complications from alcohol use disorder, 0:13:22.040 --> 0:13:24.560 and so that's when, you know, it was sort of shocking. 0:13:24.679 --> 0:13:28.160 Even though at some level it was this was going 0:13:28.240 --> 0:13:32.400 to happen, the question was exactly how and when. And 0:13:32.440 --> 0:13:35.640 he had completely estranged himself from our family at that point, 0:13:36.120 --> 0:13:39.800 which was very sad and stressful, so that when he 0:13:39.880 --> 0:13:42.319 died it was sort of this big change, you know, 0:13:42.559 --> 0:13:45.840 in my day to day kind of worry and thinking 0:13:45.920 --> 0:13:48.480 about what was going on, and that allowed me to 0:13:48.520 --> 0:13:52.120 have some time to reflect on Wow, really they were 0:13:52.160 --> 0:13:56.480 similar things. My dad using alcohol made by yeast, you know, 0:13:56.559 --> 0:13:59.280 to keep enemies at bay, and sort of my own 0:13:59.320 --> 0:14:02.880 work in my life, you know, studying a species that 0:14:02.960 --> 0:14:05.679 was doing something similar to keep its enemies at bait. 0:14:05.800 --> 0:14:08.280 Just that the enemies are really different. One was sort 0:14:08.320 --> 0:14:10.560 of choosing to do it, or at least went down 0:14:10.600 --> 0:14:13.840 that path right, and the other is innate in the 0:14:13.880 --> 0:14:16.960 case of the monarch, And so the similarities and differences 0:14:17.760 --> 0:14:20.640 were sort of woven together in my mind, and I 0:14:20.680 --> 0:14:23.080 hadn't known it really up until that point. So it 0:14:23.120 --> 0:14:25.960 was it was an awakening his death I think of 0:14:26.040 --> 0:14:30.360 reflecting on, you know, human use of chemicals, which I 0:14:30.400 --> 0:14:33.600 had not studied really except very tangentially in my lap. 0:14:33.760 --> 0:14:37.040 So that's a long answer, but it's you can see 0:14:37.040 --> 0:14:40.840 that that it's it's this dance is a little complicated 0:14:41.040 --> 0:14:44.080 in both cases, but there is this commonality between them. 0:14:44.960 --> 0:14:47.560 And as you talked about, humans aren't the only ones 0:14:47.640 --> 0:14:50.520 to sort of co opt these toxins with the monarch, 0:14:50.560 --> 0:14:55.160 butterflies and the milkweeds. I love that story. But humans 0:14:55.320 --> 0:14:59.520 also aren't the only animals to self medicate. So could 0:14:59.560 --> 0:15:03.600 you talk about some of the research examining possible instances 0:15:03.760 --> 0:15:09.000 of self medication in either the animal or the prehistoric world. 0:15:10.240 --> 0:15:13.040 Sure, so, you know, one of the in the first 0:15:13.120 --> 0:15:17.400 chapter of the book, I focus on the sunflower family, 0:15:17.440 --> 0:15:20.560 the astorac just as a way of getting people to 0:15:20.640 --> 0:15:22.880 kind of understand how this book is going to go down. 0:15:23.960 --> 0:15:28.720 And the two themes that we regularly that I regularly 0:15:29.280 --> 0:15:32.440 revisit even in that chapter as you bring up, are 0:15:32.480 --> 0:15:37.200 the fact that animals self medicate, so that includes things 0:15:37.840 --> 0:15:41.920 as perhaps Mundane is a sparrow, so they are known 0:15:42.000 --> 0:15:45.480 to arrested sparas are known to line their nests with 0:15:46.080 --> 0:15:52.479 sprigs of wormwood artemisia, and scientists have shown that experimentally 0:15:52.520 --> 0:15:57.400 that that protects the nestlings from natural enemies like ticks 0:15:57.400 --> 0:15:59.360 and mites and things that would feed on their blood. 0:15:59.880 --> 0:16:03.400 That's really interesting, and it just so happens that the 0:16:03.440 --> 0:16:06.560 study was done in China. The sparrow the species is 0:16:06.600 --> 0:16:10.440 a rusted sparrow, and the same species of Artemisia is 0:16:10.520 --> 0:16:14.040 actually put on around door frames and hung from porches 0:16:14.400 --> 0:16:16.880 at a particular time in China that is associated with 0:16:16.920 --> 0:16:19.840 this dragon boat festival, and it's meant to sort of 0:16:19.880 --> 0:16:23.960 ward off you know, evil spirits or whatever, and maybe 0:16:24.040 --> 0:16:27.400 pests too, you know. So it's like the two things 0:16:27.400 --> 0:16:29.200 are mirroring each other. And then one of the other 0:16:29.280 --> 0:16:34.760 examples I give is chimpanzees in Africa where they're native 0:16:34.760 --> 0:16:40.720 in central Equatorial Africa, that they use this plant called Vernonia, 0:16:40.800 --> 0:16:43.640 which is another member of the sunflower family. And what 0:16:44.160 --> 0:16:47.720 people anthropologists have observed them doing and primatologists have observed 0:16:47.720 --> 0:16:51.120 them doing, is they will take these it's almost like 0:16:51.160 --> 0:16:55.800 a bush like daisy. They'll take the you know, stems 0:16:55.800 --> 0:16:59.120 of it and then to the bitter pith and then 0:16:59.480 --> 0:17:01.480 you know, skind of suck out the juices and then 0:17:01.600 --> 0:17:04.720 throw the stems away. So they're not they're not eating 0:17:04.720 --> 0:17:06.560 the stems and it doesn't look like they're doing this 0:17:06.600 --> 0:17:09.080 for nutrition at all. And one of the reasons is 0:17:09.440 --> 0:17:14.240 that plant vernonia is used by people to make food 0:17:14.440 --> 0:17:17.399 but also in medicine, and it's called bitter leaves and 0:17:17.480 --> 0:17:19.800 it's actually used to make this It's an ingredient in 0:17:19.840 --> 0:17:24.560 this stew called endo lay, and the bitter leaves are bitter, 0:17:25.280 --> 0:17:28.240 and so you really have to cook them, you know, 0:17:28.320 --> 0:17:31.399 in order to eat them. And so the chimpanzees what 0:17:31.480 --> 0:17:36.359 the primatologists showed that the vernonia bitter pith chewing is 0:17:36.400 --> 0:17:41.120 associated with, you know, seasonal variation in worm intestinal worm burdens. 0:17:41.160 --> 0:17:44.560 So they're doing this bitter pith chewing when worm burdens 0:17:44.600 --> 0:17:47.399 are high, and that seems to treat them seems to 0:17:47.400 --> 0:17:49.800 reduce the impact of the worms and their body. Now, 0:17:50.200 --> 0:17:53.760 the other mirroring thing is that local people who are 0:17:54.359 --> 0:17:57.840 living near these chimps, but not just there all over 0:17:58.080 --> 0:18:01.280 you also use vernonia as a medicine to treat various ailments, 0:18:01.320 --> 0:18:04.520 including various infectious diseases. So we see this kind of 0:18:04.520 --> 0:18:07.639 repeated pattern over and over that animals are doing it, 0:18:07.760 --> 0:18:12.760 we're doing it in our case. It's culturally transmitted information. 0:18:13.000 --> 0:18:15.200 That's the big difference, I think, and I'm not saying 0:18:15.240 --> 0:18:16.960 it's not in chimps, but I don't think we have 0:18:17.000 --> 0:18:20.000 evidence of that yet if it exists. And then the 0:18:20.080 --> 0:18:23.800 same patterns are mirrored in other places where great apes 0:18:24.080 --> 0:18:32.560 occur in nature. In Southeast Asia, orangutans use a tree 0:18:33.480 --> 0:18:36.840 in the Dressina genus, and so do local people to 0:18:36.960 --> 0:18:40.199 treat infections. So the orangutans seem to use it for 0:18:40.280 --> 0:18:43.919 skin infections, and people use it for a variety of things. 0:18:44.040 --> 0:18:45.800 And there's a sappin in which is a particular kind 0:18:45.800 --> 0:18:47.960 of chemical that's been shown to be present in the 0:18:48.119 --> 0:18:54.000 Dressina juice that may be the active ingredient that is 0:18:54.040 --> 0:18:58.520 acting pharmacologically. And then maybe the most interesting story is 0:18:59.720 --> 0:19:01.440 you know some of the and this, I would say 0:19:01.480 --> 0:19:07.960 is the most difficult to determine if it's really sort 0:19:07.960 --> 0:19:09.960 of a cause effect thing in terms of why they 0:19:09.960 --> 0:19:14.840 were doing this. But they're a very close relative of 0:19:15.040 --> 0:19:19.679 our species. Homo sapiens, which we call modern humans, is 0:19:19.720 --> 0:19:23.399 an extinct lineage that was either a subspecies or species 0:19:23.600 --> 0:19:28.199 or divergent population depending on who you're talking to. But 0:19:28.280 --> 0:19:32.000 this was what are known as the Neanderthals, Homo neanderthal 0:19:32.119 --> 0:19:36.119 ensis or Homo sapiens neanderthal ensis, depending on right was 0:19:36.160 --> 0:19:38.080 it a subspecies or not, And that's sort of a 0:19:38.280 --> 0:19:41.960 splitting of hairs thing. But we know that this lineage 0:19:42.280 --> 0:19:46.520 left Africa before Homo sapiens did and then arrived in 0:19:46.560 --> 0:19:50.959 Europe and Asia, and you know, it was pretty divergent 0:19:51.160 --> 0:19:54.640 from humans that were evolving in Africa at the same time, 0:19:54.720 --> 0:19:57.399 you know, had left sort of butted off and formed 0:19:57.400 --> 0:20:00.399 a new lineage. And they were in Europe before modern 0:20:00.480 --> 0:20:03.840 humans were, for example. But eventually modern humans made their 0:20:03.840 --> 0:20:07.520 way to Europe co existed with the Neanderthals innerbred with them. 0:20:07.600 --> 0:20:12.120 So people who are of European descent almost everyone has, 0:20:12.240 --> 0:20:14.919 you know, somewhere around three percent of the genome is 0:20:15.119 --> 0:20:19.280 Neanderthal genome, but that species as a whole has gone extinct, 0:20:19.400 --> 0:20:22.960 and the only vestiges besides the pieces of our DNA 0:20:23.280 --> 0:20:27.120 many of us that have that are skulls and skeletons 0:20:27.240 --> 0:20:29.879 that were left in caves. And so there's a cave 0:20:29.960 --> 0:20:33.840 in Spain called elc Drone where a number of Neanderthal 0:20:33.880 --> 0:20:37.879 skeletons have been identified and the genomes of those individuals 0:20:37.960 --> 0:20:42.679 have been sequenced completely in the case of this one cave, 0:20:43.240 --> 0:20:46.600 and there's this one Neanderthal in that cave named I 0:20:46.680 --> 0:20:48.880 call him Sid in the book, just kind of as 0:20:48.880 --> 0:20:51.280 a way of, you know, kind of keeping track of 0:20:51.320 --> 0:20:56.120 what we're talking about. And Sid's was an adult male Neanderthal, 0:20:56.600 --> 0:21:00.520 and he had an absessed tooth based on his you know, 0:21:00.680 --> 0:21:06.439 the information that anthropologists got from the cave and the 0:21:06.480 --> 0:21:09.360 other thing they did this is amazing. He had dental 0:21:09.400 --> 0:21:12.480 calculus on the back of his teeth, like all of 0:21:12.520 --> 0:21:18.760 these skeletons did. And what scientists did is they analyzed 0:21:18.840 --> 0:21:21.919 what was in that calculus and they found remnants of 0:21:21.960 --> 0:21:25.920 the food that Sid and the other Neanderthals were eating. 0:21:26.440 --> 0:21:29.600 And not only that, but they sequenced the DNA of 0:21:29.720 --> 0:21:32.680 whatever was in the mouth of Sid and his friend, 0:21:32.760 --> 0:21:35.200 you know, whoever else was in the cave with him 0:21:35.560 --> 0:21:40.000 who died, they weren't necessarily contemporaneous, and what they found 0:21:40.080 --> 0:21:43.400 were typical food stuffs that people would expect to Neanderthals 0:21:43.440 --> 0:21:45.679 already known to be eating at that time in the 0:21:45.760 --> 0:21:50.200 other mouths. But in Sid's mouth they found something very unique. 0:21:50.240 --> 0:21:54.720 They found evidence that Sid had been eating or consuming 0:21:55.000 --> 0:22:00.320 drinking chemicals that were from yarrow, from this another member 0:22:00.359 --> 0:22:03.800 of the sunflower family, the astracy, and one of the 0:22:03.880 --> 0:22:08.960 chemicals is called chemazuline. And you know, yarrow is used 0:22:09.000 --> 0:22:11.879 as a medicinal by lots of different peoples around the 0:22:11.880 --> 0:22:15.639 world and has been medicinally important as a plant, and 0:22:15.720 --> 0:22:20.200 chemazuline is a profin which has sort of a structure 0:22:20.240 --> 0:22:25.240 that's very similar to ibuprofen. So it's possible that chemazuline, 0:22:25.240 --> 0:22:27.320 there's some evidence that it's actually used as an anti 0:22:27.400 --> 0:22:30.000 it was used as an anti inflammatory, and still is 0:22:30.640 --> 0:22:32.880 that it has those properties. Okay, So that's one thing. 0:22:33.760 --> 0:22:37.280 And the infection that Sid had is known because the 0:22:37.400 --> 0:22:40.320 DNA of that pathogen was sequenced. When they sequenced the 0:22:40.480 --> 0:22:43.840 genome of CID which is also amazing, and then microbiome 0:22:43.840 --> 0:22:49.200 that was in his mouth, and then there was evidence 0:22:49.240 --> 0:22:53.840 that he was eating bark from a poplar tree, and 0:22:53.920 --> 0:22:59.000 poplar trees are produce a lot of something called salicilic acid, 0:22:59.480 --> 0:23:02.000 which is a chemical that is very similar to the 0:23:02.080 --> 0:23:04.919 chemical that's an aspirin acetyl cl selic acid is just 0:23:04.960 --> 0:23:08.479 a stylated clicelic acid okay, and salicilic acid on its 0:23:08.480 --> 0:23:12.240 own also as anti inflammatory affects, just like actasalicelic acid 0:23:12.280 --> 0:23:15.280 or aspirin does. They found that in his mouth. Then 0:23:15.320 --> 0:23:19.320 they also found DNA from penicillium mold, which is the 0:23:19.320 --> 0:23:24.520 mold that produces the antibiotic penicillin. So none of the 0:23:24.520 --> 0:23:27.360 other Neanderthals in the cave had this stuff. And they 0:23:27.560 --> 0:23:31.640 from the genome sequence, they figured out that sid had 0:23:31.680 --> 0:23:35.840 some gene variants that allowed him to taste and discern 0:23:36.359 --> 0:23:39.800 at a very high level bitter chemicals in food and drink, 0:23:39.880 --> 0:23:44.200 and so some humans also are tasters or not tasters 0:23:44.640 --> 0:23:46.680 of these bitter compounds. So this is why some people 0:23:46.720 --> 0:23:52.120 are really sensitive to things like cilantro or mustard greens 0:23:52.160 --> 0:23:55.280 and Brussels sprouts and some aren't. Some don't care something 0:23:55.320 --> 0:23:58.159 it's fine, some hate it, right, And so Sid was 0:23:58.200 --> 0:24:00.280 a taster. So what this meant was Sid knew what 0:24:00.359 --> 0:24:03.359 he was doing. He wasn't just eating this stuff because 0:24:03.359 --> 0:24:05.920 he didn't know what it was. That's the idea anyway, 0:24:06.000 --> 0:24:10.000 that's inferred by this fact that he had the genetic 0:24:10.080 --> 0:24:13.680 variance that might allow him to taste really bitter things. So, 0:24:13.960 --> 0:24:18.119 putting all of this together, the anthropologists have suggested that 0:24:18.320 --> 0:24:22.520 Sid was self medicating. And that is old evidence, fifty 0:24:22.560 --> 0:24:28.280 thousand year old evidence that perhaps our ancestors, our closest relatives, 0:24:28.560 --> 0:24:31.639 we're doing what we do now that every single person 0:24:31.680 --> 0:24:35.480 has done right and the home remedies are maybe that's 0:24:35.480 --> 0:24:40.800 what Sid was using, what his family, his ancestors were doing. 0:24:40.840 --> 0:24:43.040 So how far back can we go? And that's where 0:24:43.040 --> 0:24:46.480 the great ape thing becomes interesting, because our closest living relatives, 0:24:46.480 --> 0:24:49.360 those great apes, also do it. So then we put 0:24:49.400 --> 0:24:51.480 all this together, we say, well, this seems to be 0:24:51.840 --> 0:24:54.960 maybe millions of years old, this practice right in the 0:24:54.960 --> 0:24:57.880 primate lineage and our specific great ape lineage. 0:24:59.000 --> 0:25:01.359 Let's take a quick break, and when we get back, 0:25:01.480 --> 0:25:19.880 there's still so much to discuss. Welcome back everyone, I've 0:25:19.880 --> 0:25:23.000 been chatting with doctor Noah Whitman about his book Most 0:25:23.080 --> 0:25:28.680 Dangerous Poison. Let's get back into things. It is so fascinating. 0:25:29.080 --> 0:25:31.840 There are sometimes doing the podcast where I think I 0:25:31.880 --> 0:25:34.320 want to go back and get another PhD in this, 0:25:34.400 --> 0:25:36.520 and then I'm like, talk myself out of it immediately. 0:25:36.560 --> 0:25:39.440 But like, that is definitely an area that I could 0:25:39.480 --> 0:25:44.240 would love to explore more. But as you discuss, there 0:25:44.320 --> 0:25:48.800 is also tremendous diversity in just the number and kind 0:25:48.960 --> 0:25:53.000 or types of toxins that plants can produce. Can the 0:25:53.160 --> 0:25:57.320 type of toxin produced tell us anything about what it's 0:25:57.480 --> 0:26:00.840 used for or the species that a plant it interacts with. 0:26:02.320 --> 0:26:06.280 Yeah, so, as you say, you know, plants and fungi 0:26:06.480 --> 0:26:10.639 and bacteria and our chaia, and you know even animals 0:26:10.680 --> 0:26:15.520 and protus are all capable of making chemicals that are toxic. 0:26:16.200 --> 0:26:19.240 And you know, one of the things to think about 0:26:19.320 --> 0:26:21.800 is like, well even oxygen is toxic, right, So what 0:26:21.960 --> 0:26:25.879 is a toxin? And for the purposes of the book, 0:26:26.040 --> 0:26:29.239 the way I think about it is, you know, is 0:26:29.359 --> 0:26:32.960 the organism making it to defend itself or to manipulate, 0:26:33.320 --> 0:26:36.400 you know, another organism, the behavior of another organism, either 0:26:36.440 --> 0:26:39.240 to repel it or attract it. And you know, a 0:26:39.280 --> 0:26:42.280 toxin isn't going to attract something necessarily, but a toxin 0:26:42.320 --> 0:26:45.199 could manipulate the mind of something. And so like a 0:26:45.200 --> 0:26:49.040 citrus plant will put caffeine that it makes in the 0:26:49.080 --> 0:26:52.359 nectar to manipulate the minds of bees. And it's not 0:26:52.400 --> 0:26:55.480 like the plant is thinking. It's not conscious. Plants don't 0:26:55.480 --> 0:26:58.000 have brains. They're not conscious in the same way we 0:26:58.080 --> 0:27:01.680 define an animal that has a right. So that's one thing. 0:27:02.040 --> 0:27:04.440 It doesn't mean they're not sensing the environment or responding 0:27:04.520 --> 0:27:06.320 to it, because of course they are all the time, 0:27:06.359 --> 0:27:11.560 so they have very sophisticated environmental sensing equipment. But they've 0:27:11.560 --> 0:27:14.080 been selected to do this. That means they've the ones 0:27:14.119 --> 0:27:16.680 that do it have been favored to do it. And 0:27:16.960 --> 0:27:20.959 the mutations that occur in the gene pathway, in the 0:27:21.040 --> 0:27:25.040 metabolic pathways that are encoded by genes that encode enzymes 0:27:25.119 --> 0:27:28.320 right that make the metabolism happen, those are the things 0:27:28.359 --> 0:27:31.240 that have been selected on those random variants that tweak 0:27:31.320 --> 0:27:36.080 the chemical structures, and the ones that survive better leave 0:27:36.160 --> 0:27:38.960 more offspring are the ones that pass those traits on 0:27:39.080 --> 0:27:42.040 to the next generation. That's Darwinian evolution, right, We know 0:27:42.119 --> 0:27:46.000 that that is how most of these chemicals arose, and 0:27:46.440 --> 0:27:51.280 they are making these ornate often very expensive chemicals in 0:27:51.359 --> 0:27:54.600 terms of energy and also just what's in them. So 0:27:54.680 --> 0:27:56.639 a lot of them have a nitrogen atom in them, 0:27:56.680 --> 0:27:59.760 at least one that's expensive because they could be putting 0:27:59.800 --> 0:28:03.440 that into making pollen or seeds depending on the organism, 0:28:03.560 --> 0:28:06.240 or spores or eggs in the case of an animal. 0:28:06.400 --> 0:28:08.960 Why are they making Why are they doing this? And 0:28:09.000 --> 0:28:11.280 we know that when you prevent them from doing it 0:28:11.359 --> 0:28:14.320 by knocking the genes out or you know, the opposite, 0:28:14.400 --> 0:28:16.560 taking the chemical and sprain it on a plant that 0:28:16.600 --> 0:28:19.800 doesn't make it, like say caffeine. If you put caffeine 0:28:19.800 --> 0:28:23.560 on a tomato leaf, they're very well defended from herbivores, 0:28:23.560 --> 0:28:27.280 including the ones that can normally attack tomatoes. So all 0:28:27.320 --> 0:28:29.360 of this evidence you know when you knock them out, 0:28:29.400 --> 0:28:31.480 when you knock the genes out that make the toxins 0:28:31.560 --> 0:28:33.760 in plants and you put them out in nature, they 0:28:33.800 --> 0:28:36.480 don't do very well. They get attacked by insects and 0:28:36.560 --> 0:28:39.920 other animals. So we know that they serve that function. 0:28:40.160 --> 0:28:43.960 They protect the plant from being eaten and that allows 0:28:44.040 --> 0:28:48.200 them to have more pollen and seeds than they would otherwise. Right, 0:28:48.320 --> 0:28:51.200 because they have they can protect that tissue that is 0:28:51.200 --> 0:28:55.000 allowing them to photosynthesize, that's allowing them to make more 0:28:55.000 --> 0:28:59.440 seeds in pollen. So it's this defense usually that has 0:28:59.440 --> 0:29:03.480 evolved in the plants against natural enemies, and the natural 0:29:03.600 --> 0:29:06.240 enemies have been the ones doing the natural selection. They're 0:29:06.280 --> 0:29:09.400 the selective agents, as we say, so we can only 0:29:09.440 --> 0:29:11.240 think about it in the context of this kind of 0:29:11.320 --> 0:29:16.120 coevolved system. But eventually some animals overcome that and even 0:29:16.280 --> 0:29:18.120 use the chemicals that the plants are making to their 0:29:18.120 --> 0:29:21.320 own devices, like the monarch butterfly. So when if we 0:29:21.360 --> 0:29:24.200 step way back, we can say that many of the 0:29:24.240 --> 0:29:26.960 plants that are out there, the species that are out there, 0:29:27.000 --> 0:29:30.000 the diversity of plants, and you know, if we look 0:29:30.040 --> 0:29:33.320 at their chemicals, they're so diverse among those plants, right, 0:29:33.360 --> 0:29:36.040 each one is sort of making a different set. And 0:29:36.080 --> 0:29:39.000 then yes, there's some similarity among plants that are closer 0:29:39.080 --> 0:29:41.560 related to each other and the chemicals they make, but 0:29:41.600 --> 0:29:45.360 there's also diversity that's constantly being born in the chemical 0:29:45.360 --> 0:29:49.160 structures as time goes on, as evolution proceeds. And then 0:29:49.200 --> 0:29:51.440 the same is true in the animal side. You know 0:29:51.520 --> 0:29:54.400 that they're colonizing these plants, they're having to overcome these 0:29:54.400 --> 0:29:57.400 things and evolve ways of dealing with them and sometimes 0:29:57.400 --> 0:30:01.720 even using them. So this chemical dance has produced all 0:30:01.760 --> 0:30:05.200 of these diverse chemicals over deep time, this co evolutionary 0:30:05.280 --> 0:30:09.120 dance in the plants and the other organisms that are 0:30:09.120 --> 0:30:11.240 making them. So that's that's I would say the most 0:30:11.240 --> 0:30:14.320 important thing to realize is that these chemical this chemical 0:30:14.320 --> 0:30:17.560 diversity isn't there, you know, because of us. We can 0:30:17.640 --> 0:30:22.120 benefit from it by tapping into this you know, war 0:30:22.160 --> 0:30:26.360 of nature, but the chemical diversity itself is there to 0:30:26.520 --> 0:30:29.000 serve the needs of the makers. 0:30:30.200 --> 0:30:32.760 I love that point because I think that we're so 0:30:33.280 --> 0:30:35.760 of course, most of us are so human centric that 0:30:35.840 --> 0:30:38.320 we think about but what about humans? But what about us? 0:30:38.360 --> 0:30:41.040 But what about us? And I think that it goes 0:30:41.080 --> 0:30:45.120 to show that some of these plant derived pharmaceuticals we 0:30:45.440 --> 0:30:49.040 forget their you know, their plant origins. But there are 0:30:49.080 --> 0:30:54.960 some amazing, serendipitous stories of how we discovered certain drugs, 0:30:55.080 --> 0:30:58.520 very effective drugs, like I think one in your book 0:30:58.560 --> 0:31:02.560 that you mentioned is Humoran and Warfarin and cattle. Do 0:31:02.720 --> 0:31:06.080 you have a favorite drug origin story. 0:31:06.560 --> 0:31:09.160 Yeah, that's one that I didn't really know about before 0:31:09.160 --> 0:31:11.800 I started writing the book, but is it really interesting. Yeah. 0:31:11.840 --> 0:31:15.520 So the blood thinner warfarin that is a very important 0:31:15.560 --> 0:31:19.400 anti cregulent drug, is also a rat poison and is 0:31:19.440 --> 0:31:21.600 a big problem right now because if people leave out 0:31:21.680 --> 0:31:24.560 rat poison, you know, in their backyard, and a rat 0:31:24.600 --> 0:31:27.280 eats it but doesn't quite die, a bird of prey 0:31:27.360 --> 0:31:30.280 might eat that rat and become poisoned. So this is 0:31:30.320 --> 0:31:32.520 actually a big problem and I don't think people should 0:31:32.520 --> 0:31:39.240 be using rat poison. But my favorite origin story really 0:31:39.360 --> 0:31:44.280 is probably curari, which is a concoction. So that's a 0:31:44.360 --> 0:31:47.200 general term for a concoction that is used as an 0:31:47.240 --> 0:31:51.840 air poison all over northern South America and the Caribbean. 0:31:52.240 --> 0:31:55.640 So curari is not just one thing. And these are 0:31:56.000 --> 0:32:02.160 concoctions that were recipes basically passed down the generations, and 0:32:02.200 --> 0:32:07.040 they're derived from different plants, mostly in the Amazonian rainforest. 0:32:07.760 --> 0:32:12.040 And one of them is called tube kurari and that 0:32:12.240 --> 0:32:15.760 was simply because the qurrari was stored in bamboo when 0:32:15.760 --> 0:32:20.360 it was shipped to North America and Europe where it 0:32:20.440 --> 0:32:26.040 was analyzed. But indigenous peoples were in that case in 0:32:26.200 --> 0:32:30.520 Ecuador were using tube kurrai as an aero poison for 0:32:30.600 --> 0:32:34.520 hunting mostly but also in warfare, but mostly in hunting 0:32:34.560 --> 0:32:40.160 and blow darts. And the German explorer Alexander von Humboldt 0:32:40.560 --> 0:32:44.600 in his diary along with Amy Boone Plant his companion, 0:32:45.200 --> 0:32:50.160 they described their encounter in I think Brazil with an 0:32:50.160 --> 0:32:53.960 indigenous man who was the man who was making the 0:32:54.040 --> 0:32:56.040 kirai in that village that he happened to be in, 0:32:56.480 --> 0:32:59.920 and he was having a conversation with the kurari maker. 0:33:00.880 --> 0:33:03.800 But he described the place where he was making it 0:33:03.840 --> 0:33:06.560 as similar to a pharmacy that you would encounter in 0:33:06.600 --> 0:33:11.520 Europe with you know, with very sophisticated filters and vessels 0:33:11.640 --> 0:33:15.440 and you know, lots of very particular ways of doing things. 0:33:16.000 --> 0:33:17.960 And then the man who was making the karari said 0:33:18.000 --> 0:33:20.520 that they called the silent death. You know. His claim 0:33:20.560 --> 0:33:22.959 was that it was far superior to gunpowder because it 0:33:23.000 --> 0:33:24.840 was quiet, you know, it was didn't make a sound, 0:33:25.400 --> 0:33:28.760 and so you could could shoot a prey in the 0:33:28.800 --> 0:33:30.880 tree with a blow dart and it would hit the 0:33:30.960 --> 0:33:34.160 animal and then you know, maybe thirty seconds later. Because 0:33:35.040 --> 0:33:38.360 what became determined was that the chemical in that qurrai 0:33:38.640 --> 0:33:42.560 was paralyzing the animal. And the animal was still alive 0:33:42.600 --> 0:33:45.000 when it fell to the ground, but paralyzed, couldn't breathe right, 0:33:45.040 --> 0:33:49.479 eventually died. So these concoctions were used all over you know, 0:33:49.640 --> 0:33:52.840 northern South America and the Amazonian basin and were very valuable. 0:33:52.840 --> 0:33:56.120 They were traded, they were coveted things, these aero poisons. 0:33:56.720 --> 0:34:00.320 But that tube Kurari that was eventually shipped in the 0:34:00.360 --> 0:34:06.400 twentieth century to be analyzed, and in both Canada and Europe, 0:34:06.440 --> 0:34:09.640 it was sort of discovered that okay, this tube curari 0:34:10.360 --> 0:34:16.200 had a compound and alkaloid, that tubocurarin, that became the 0:34:16.440 --> 0:34:21.600 first muscle relaxant that allowed general anesthesia to proceed in 0:34:21.960 --> 0:34:24.960 the modern way that we think about during surgery. So 0:34:25.000 --> 0:34:29.040 it was a stabilized kind of anesthesia that wasn't just ether, right, 0:34:29.040 --> 0:34:31.839 which would knock you out. But the problem was if 0:34:32.120 --> 0:34:35.640 the muscles weren't relaxed during surgery, it made it very 0:34:35.680 --> 0:34:38.360 dangerous for the patient and very difficult for the surgeon. 0:34:38.440 --> 0:34:40.840 Right you can imagine why if the muscles are reacting 0:34:41.360 --> 0:34:42.960 to being cut, that's not a good thing. 0:34:43.080 --> 0:34:43.279 Right. 0:34:43.719 --> 0:34:47.759 So this this currari totally relaxed the skeletal muscles and 0:34:47.840 --> 0:34:51.480 allowed surgery to be performed in a way that was stable, 0:34:51.600 --> 0:34:55.320 so etherized and curized. And so that's probably my favorite 0:34:55.320 --> 0:34:58.839 origin story because it arose from indigenous knowledges. They knew 0:34:58.880 --> 0:35:01.440 it was paralyzing the animals, that's why they were using it, 0:35:02.160 --> 0:35:04.239 but not just it. It's like many things, but this 0:35:04.320 --> 0:35:07.400 one specific one actually had. It played an enormous role 0:35:07.800 --> 0:35:10.400 in the development of modern medicine and eventually led to 0:35:10.440 --> 0:35:14.120 the ventilator because if you are paralyzing the skull of 0:35:14.200 --> 0:35:16.560 muscles during surgery, as anybody knows, you have to be 0:35:16.560 --> 0:35:19.399 put on a ventilator and have to have artificial respiration, right, 0:35:20.040 --> 0:35:23.080 So it led to the development of all this technology 0:35:23.120 --> 0:35:26.080 that we take for granted now. But it's important to 0:35:26.120 --> 0:35:29.320 remember that this was really only going in the nineteen 0:35:29.520 --> 0:35:33.920 forties or so, right, so before that it was this 0:35:33.960 --> 0:35:36.319 is why surgery is still dangerous, but it was a 0:35:36.360 --> 0:35:39.080 lot more dangerous then. So that's probably my favorite story. 0:35:39.880 --> 0:35:43.840 It's a great story, and we oh, like modern medicine, 0:35:43.920 --> 0:35:48.960 modern surgery owes so much to various plant compounds like 0:35:49.040 --> 0:35:53.840 kirari and morphine is another one that you mentioned, but 0:35:54.480 --> 0:35:57.840 one of the most jaw dropping and mind blowing facts 0:35:57.880 --> 0:36:01.600 that I read in your book is that mammals have 0:36:01.719 --> 0:36:06.560 been making morphine long before plants and salsilic acid we 0:36:06.640 --> 0:36:10.480 make our own. But what the heck is going on? Why? How? 0:36:10.880 --> 0:36:15.320 Yeah? I would say that this is still a pretty 0:36:15.760 --> 0:36:20.680 controversial topic in just in terms of the science, but 0:36:21.200 --> 0:36:23.439 as I review it in the book, I mean, I'm 0:36:23.480 --> 0:36:27.200 convinced that you know, based on the published studies, that 0:36:27.400 --> 0:36:31.480 mammals do make salsilic acid for whatever function. We don't 0:36:31.600 --> 0:36:35.040 know yet, Actually we don't know. And the reason that 0:36:35.640 --> 0:36:38.040 we think this, it's like, yes, it could be the 0:36:38.080 --> 0:36:41.759 microbiome making it or something, right, but in studies with 0:36:41.840 --> 0:36:44.719 like mice, you know where they really control well the 0:36:44.840 --> 0:36:47.200 diet and things like that, they are still making it. 0:36:47.280 --> 0:36:50.239 So you can even have notobiotic mice, which means mice 0:36:50.280 --> 0:36:53.120 that don't have a microbiome, so they're sterile. But the 0:36:53.160 --> 0:36:56.759 morphine thing, I think is actually more interesting because we 0:36:56.840 --> 0:37:01.200 have receptors for morphine that are called the endorphin, and 0:37:01.320 --> 0:37:05.040 the endorphins are these peptides, which means they're they're amino 0:37:05.080 --> 0:37:08.800 acids that are kind of linked together. Right in chains 0:37:08.840 --> 0:37:12.400 not super long because they don't fold into proteins, but 0:37:12.480 --> 0:37:15.600 all proteins are made of these chains of amino acids too, 0:37:15.840 --> 0:37:20.280 So shorter ones are just called peptides, and endorphins are those. 0:37:20.360 --> 0:37:23.239 They're peptides of amino acids, made of amino acids, and 0:37:23.280 --> 0:37:26.480 they bind to the endorphin receptors. And so say if 0:37:26.560 --> 0:37:29.600 I had a paper cut in my hand, endorphins would 0:37:29.600 --> 0:37:32.360 be released, right, so I would initially feel pain, but 0:37:32.360 --> 0:37:34.759 then the pain gets dulled, and that dulling is in 0:37:34.800 --> 0:37:37.680 part due to the release of these endorphins. Okay, so 0:37:37.760 --> 0:37:42.640 they are the pain sort of preventing molecules that allow 0:37:42.760 --> 0:37:48.799 us to calm the pain down. And morphine binds to 0:37:48.880 --> 0:37:52.080 those receptors too, And it was thought that morphine is 0:37:52.120 --> 0:37:54.800 only found in the opium poppy, and the opium poppy's 0:37:54.840 --> 0:37:57.840 relatives make similar compounds, but nothing quite gets to morphine 0:37:57.840 --> 0:38:01.120 except in the opium poppy, and the pathway, the metabolic 0:38:01.160 --> 0:38:06.320 pathway to make morphine is well characterized in opium poppies, 0:38:06.360 --> 0:38:11.160 and we roughly know, you know, when the different relatives 0:38:11.719 --> 0:38:14.000 gained the ability to make the precursors and things like that. 0:38:14.040 --> 0:38:18.960 So it's pretty ancient And it turns out this researcher 0:38:19.040 --> 0:38:24.600 in Saint Louis, this late scientist, discovered some evidence that 0:38:25.320 --> 0:38:32.200 the brains of mammals and other body parts contained morphine. 0:38:32.880 --> 0:38:35.920 He could even find it in the urine of some animals. 0:38:35.960 --> 0:38:38.880 And you know, this was actually older evidence, and people 0:38:38.920 --> 0:38:41.000 were sort of like, yeah, well, it's just what they're eating, 0:38:41.160 --> 0:38:43.040 or you know, they're getting it from the diet. If 0:38:43.040 --> 0:38:46.000 they're cows, they're probably eating poppies or things like that, 0:38:46.640 --> 0:38:48.719 or maybe it's the bacteria and their guts making it 0:38:48.800 --> 0:38:53.040 or transforming some chemical into a morphine like chemical. But 0:38:53.560 --> 0:38:56.160 he went a step further and actually looked at this 0:38:56.320 --> 0:38:59.160 in mice. So he had mice that were which are 0:38:59.200 --> 0:39:01.680 mammals like us, and should do mice make it? Because 0:39:01.719 --> 0:39:03.839 if we make it, maybe mice make it. Maybe it's 0:39:03.840 --> 0:39:07.480 something that is more conserved across the tree of life, 0:39:07.560 --> 0:39:11.000 you know. And he had these notobiotic mice that didn't 0:39:11.000 --> 0:39:14.600 have microbiomes. He delivered them via cesarean section so that 0:39:15.080 --> 0:39:19.560 they're very controlled mice that don't have a microbiome. They 0:39:20.200 --> 0:39:23.319 have a diet that's very very controlled. And sure enough, 0:39:23.360 --> 0:39:26.440 those mice in the urine also had morphine. It's like, where, 0:39:26.520 --> 0:39:28.960 so is this just a byproduct? Like what is going on? 0:39:29.040 --> 0:39:32.799 How do they do this? People were skeptical still, so 0:39:33.280 --> 0:39:36.960 he went a step further and had some human cell lines. 0:39:37.000 --> 0:39:41.200 The means they're just the cells. They were also notautobiotics, 0:39:41.280 --> 0:39:43.120 so you know, going to great lengths to make sure 0:39:43.120 --> 0:39:45.360 there are no bacteria or other microbes living in the 0:39:45.400 --> 0:39:49.359 culture with them or other cells, and he gave them 0:39:49.440 --> 0:39:54.280 a very simple precursor that eventually leads to the production 0:39:54.320 --> 0:39:58.720 of morphine in the opium poppies. So he gave those cells, 0:39:59.040 --> 0:40:01.520 you know, sort of fe the cells this precursor, and 0:40:01.520 --> 0:40:05.719 sure enough they make morphine. So it's very clear that 0:40:05.840 --> 0:40:08.080 human cells. Those were human. I think it was it 0:40:08.120 --> 0:40:11.680 was a brain tumor cell line. But this was shocking. 0:40:11.760 --> 0:40:14.360 I think that that they found morphine was able to 0:40:14.360 --> 0:40:17.440 be made by these particular cells. And then they proposed 0:40:17.520 --> 0:40:20.240 that maybe it's in the brain. Maybe maybe it actually 0:40:20.320 --> 0:40:23.840 is used somehow by the body as a molecule to 0:40:24.040 --> 0:40:27.520 do the the you know, to make these nervous systems work. 0:40:27.600 --> 0:40:30.400 But it's still unclear actually what it's doing. We don't know. 0:40:31.000 --> 0:40:33.080 So that's the bottom line is that it's it's in 0:40:33.160 --> 0:40:36.719 low amounts, but is it in amounts that are biologically meaningful? 0:40:36.840 --> 0:40:39.680 I think that's still a little controversial. Even is it 0:40:39.800 --> 0:40:42.560 just a waste product of some other metabolic pathway. We 0:40:42.680 --> 0:40:46.720 don't know, so I think there are many mysteries still. 0:40:46.760 --> 0:40:50.000 But it's shock. It's shocking, Yes, that I would say 0:40:50.080 --> 0:40:53.320 with some confidence that you and I made morphine today. 0:40:54.280 --> 0:40:54.640 It is. 0:40:55.360 --> 0:40:59.080 I just keep thinking about it. It's like so tantalizing, 0:40:59.120 --> 0:41:02.600 like why but why but why? I just keep thinking 0:41:02.600 --> 0:41:03.160 about it. 0:41:04.200 --> 0:41:07.400 But well, we're making endorphins. We know why that is. 0:41:07.440 --> 0:41:09.759 So maybe morphine is a similar thing, except it's a 0:41:09.760 --> 0:41:12.319 small molecule, you know, so it might be a little 0:41:12.320 --> 0:41:15.360 bit easier for it to get through different parts of 0:41:15.360 --> 0:41:17.960 our bodies, right, So that that's something else to think about. 0:41:18.239 --> 0:41:23.520 Yeah, And morphine, you know, is just one of many, 0:41:23.600 --> 0:41:27.640 many different types of compounds that are addictive to humans 0:41:27.719 --> 0:41:31.000 or can be addictive to humans. And a big focus 0:41:31.200 --> 0:41:34.480 of your book is on addictive compounds and your father's 0:41:34.480 --> 0:41:39.880 addiction struggles. As you mentioned, do all addictive compounds work 0:41:40.040 --> 0:41:43.080 on the human brain, I'll say, in the same way 0:41:43.239 --> 0:41:47.320 to create those addiction pathways, and Ken this is a 0:41:47.360 --> 0:41:51.160 two parter. Sorry, but can we predict whether a newly 0:41:51.239 --> 0:41:56.440 discovered toxin would be addictive or psychedelic or what effects 0:41:56.480 --> 0:41:58.920 it's likely to have just based on its structure? 0:42:00.920 --> 0:42:03.840 Well, I think in many ways, yes, you could say, 0:42:03.880 --> 0:42:06.680 this chemical what receptors does it bind too that we 0:42:06.719 --> 0:42:09.520 know of? Right, Like, we could figure that out pretty easily, 0:42:11.080 --> 0:42:12.640 and that is in fact, how a lot of drugs 0:42:12.680 --> 0:42:14.759 are designed now, you know, like where are they going 0:42:14.840 --> 0:42:17.720 to bind? And are they going to compete with another receptor? 0:42:17.760 --> 0:42:19.839 Are they going to compete with a neurotransmitter? Are they 0:42:19.880 --> 0:42:22.719 you know, what are they? Where are they binding? So 0:42:22.760 --> 0:42:26.520 I think that part is not completely understood in terms 0:42:26.520 --> 0:42:28.319 of being able to predict, but we could we can 0:42:28.360 --> 0:42:31.000 get close. Like fentanyl was sort of you know, this 0:42:31.120 --> 0:42:35.880 pipuriodine structure that forms the basis of it that was 0:42:36.040 --> 0:42:40.680 used sort of because Jansen discovered that, you know, morphine 0:42:40.760 --> 0:42:43.640 has at its base this piperiodine ring too, you know, 0:42:44.040 --> 0:42:46.880 so could he exploit that and make a synthetic version 0:42:47.160 --> 0:42:49.759 that was sort of had properties that were made it 0:42:49.840 --> 0:42:53.120 advantageous to use, And yes it did, but it also 0:42:53.160 --> 0:42:57.399 had the problem of being really really really potent, and 0:42:57.480 --> 0:43:02.239 so fentanyl is just the latest way in the opioid crisis, right. 0:43:03.320 --> 0:43:07.040 But going back to your question about addiction, well, I 0:43:07.080 --> 0:43:09.000 think the first thing to say is I'm not an 0:43:09.000 --> 0:43:13.719 addiction specialist, so that's one thing. But if you take 0:43:14.440 --> 0:43:17.880 something like alcohol use disorder and compare it to opioid 0:43:18.000 --> 0:43:21.840 use disorder, there are similarities and differences in the neural 0:43:21.920 --> 0:43:25.840 circuits involved. The same is true for something like methamphetamine 0:43:25.920 --> 0:43:29.319 use disorder. But what they have in common is, you know, 0:43:29.760 --> 0:43:33.839 very often it's either that sort of dopamine or opioid 0:43:34.120 --> 0:43:39.320 endogenous opioid in other words, endorphin based systems that are involved. 0:43:39.320 --> 0:43:42.800 Not always, but they're they're usually involved, right, So there's 0:43:42.840 --> 0:43:48.880 some some problem with those two pathways, usually in the 0:43:48.920 --> 0:43:52.120 brains of people who become addicted to things. So that's 0:43:52.160 --> 0:43:54.840 one of the things that I think most addiction specialists 0:43:54.840 --> 0:43:57.640 would agree that the people who are most prone to 0:43:57.680 --> 0:44:01.080 developing the use disorders, whether it's alcohol use disorder, opioid 0:44:01.160 --> 0:44:05.880 use disorder, something like methamphetamine use disorder, are people who 0:44:05.920 --> 0:44:11.400 come from childhoods where there was adverse events, abuse, or neglect, 0:44:11.640 --> 0:44:15.800 or all three trauma of some kind. So this book, 0:44:16.200 --> 0:44:20.440 this Gobbor mates book. It's in the Realm of Something Ghosts. 0:44:20.440 --> 0:44:22.919 I can't remember the full title, but it's a great 0:44:22.960 --> 0:44:25.320 book because he talks about this. He sort of breaks 0:44:25.360 --> 0:44:28.720 it down into the systems that get set in place 0:44:28.760 --> 0:44:33.480 as infants through early childhood. Right, These dopamine systems, the 0:44:33.520 --> 0:44:37.360 opioid system the systems that are allowing our bodies and 0:44:37.440 --> 0:44:41.520 brains to work properly, to respond to stimuli properly. But 0:44:41.600 --> 0:44:44.399 they need feedback, They need interaction with the people around 0:44:44.480 --> 0:44:47.319 us in order to develop properly. They need that kind 0:44:47.360 --> 0:44:51.480 of stimulation, right, They need to feel we need to 0:44:51.480 --> 0:44:55.080 feel safe in order to properly develop. And when that goes, 0:44:55.440 --> 0:44:59.560 when that's out of whack, then there becomes the need 0:44:59.600 --> 0:45:03.880 for external you know, sort of external stimulation or damping 0:45:03.920 --> 0:45:06.920 down of those pathways. So it's a really rough way 0:45:06.960 --> 0:45:09.680 of describing it, but I would say that people begin 0:45:09.760 --> 0:45:13.319 to use these drugs, they take them, like most people 0:45:13.360 --> 0:45:16.680 who take prescription opioids do not become do not develop 0:45:16.719 --> 0:45:19.920 opid use disorders. Right, So why do the people who 0:45:20.000 --> 0:45:22.280 develop them develop them? What do they have in common? 0:45:22.840 --> 0:45:25.200 And one of the things they have many of them 0:45:25.280 --> 0:45:29.960 have in common, are these early childhood issues with their environment, 0:45:30.800 --> 0:45:34.520 and so they're sort of set on a trajectory where 0:45:34.520 --> 0:45:39.040 they're open to developing these use disorders very easily. And 0:45:39.239 --> 0:45:42.600 that's also true for alcohol use disorder. So there's a 0:45:42.600 --> 0:45:47.040 genetic component too though, so we know that in some cases, yes, 0:45:47.080 --> 0:45:49.919 if you have certain opiid receptor variants, you are more 0:45:49.920 --> 0:45:52.399 prone to developing a use disorder. You may be more 0:45:52.400 --> 0:45:56.400 prone to developing alcohol use disorder and an opioid use disorder. 0:45:56.719 --> 0:45:59.200 So that's interesting too, and there's some debate about that 0:45:59.280 --> 0:46:01.440 as well, like does it crossover, which kind of gets 0:46:01.480 --> 0:46:07.800 at your question. But the psychedelic thing is interesting because psychedelics, 0:46:07.840 --> 0:46:13.120 broadly speaking, are just those chemicals that are binding primarily 0:46:13.239 --> 0:46:15.719 in terms of how we think about a psychedelic to 0:46:15.800 --> 0:46:18.240 a set of serotonin receptors in the brain, a subset 0:46:18.280 --> 0:46:21.640 of them, and they are not addictive in that in 0:46:21.680 --> 0:46:23.520 the ways that you and I have been talking about. 0:46:23.600 --> 0:46:27.160 So there's no use disorder known that really is going 0:46:27.239 --> 0:46:31.120 to come from a psychedelic experience, so you don't people 0:46:31.160 --> 0:46:33.680 don't get addicted to them in that kind of same sense, 0:46:34.200 --> 0:46:36.520 And what addiction is is sort of like, you know, 0:46:37.440 --> 0:46:40.160 how do we define that most people would define it 0:46:40.200 --> 0:46:44.080 as you know, using a chemical in this case in 0:46:44.120 --> 0:46:47.920 a way that causes us harm or we want to stop, 0:46:47.960 --> 0:46:51.920 but can't you know? So that there's the inability to 0:46:52.000 --> 0:46:56.160 stop using something and the continued use of it is 0:46:56.200 --> 0:46:59.239 causing problems in other areas of our life. Now you 0:46:59.239 --> 0:47:02.920 could say I'm a addicted to caffeine. Is that a problem? No? 0:47:03.360 --> 0:47:06.440 Does it cause problems in my other parts of my life? No? 0:47:07.160 --> 0:47:10.640 It enhances other parts of my life. So is that 0:47:10.719 --> 0:47:13.080 an addiction? And I think that's why the word use 0:47:13.120 --> 0:47:16.719 disorder is better than addiction because it right it sort of, 0:47:17.600 --> 0:47:19.719 it narrows it down a little bit more as a 0:47:19.760 --> 0:47:25.080 problem because it's affecting your other aspects of your life, 0:47:25.120 --> 0:47:27.479 whether it's your health or your well being. 0:47:28.760 --> 0:47:35.480 You mentioned caffeine. Coffee is my particular favorite root of caffeine, 0:47:35.560 --> 0:47:39.440 getting caffeine in my body. I have been drinking French 0:47:39.520 --> 0:47:44.040 press coffee for well over ten years. But now after 0:47:44.080 --> 0:47:47.520 reading your book, I'm having second thoughts. Can you talk 0:47:47.560 --> 0:47:50.719 about why we should consider filtering our coffee? 0:47:51.160 --> 0:47:54.080 Sure so? And these are just from the published litera 0:47:54.120 --> 0:47:57.400 scientific literature. I'm not a nutritionist. I can't give dietary advice. 0:47:57.400 --> 0:47:59.960 I'm not a physician, so keep all this in mind, okay, 0:48:00.520 --> 0:48:01.920 And I wrote about it in the books from the 0:48:01.920 --> 0:48:04.480 perspective of changing my own behavior, my own decisions I 0:48:04.520 --> 0:48:06.680 made based on my reading of the literature, So keep 0:48:06.680 --> 0:48:08.560 that in mind. So I'm not telling you or your 0:48:08.600 --> 0:48:11.360 listeners what they should be doing. I'm not giving that advice. 0:48:11.480 --> 0:48:16.680 But I personally will not drink regularly out of a 0:48:16.719 --> 0:48:21.160 French press or drink unfiltered coffee in large quantities ever. Again, 0:48:21.960 --> 0:48:26.160 and the reason is, it's a long story, but to 0:48:26.280 --> 0:48:30.080 boil it down, so to speak, it was actually boiled 0:48:30.239 --> 0:48:34.400 Scandinavian coffee, which is unfiltered. It's a way that coffee 0:48:34.440 --> 0:48:39.040 was traditionally made in Scandinavia, including Finland. And an initial 0:48:39.160 --> 0:48:42.799 set of epidemiological studies came out that were strange. They 0:48:42.800 --> 0:48:46.600 were showing that, particularly for men, there was a higher 0:48:46.680 --> 0:48:50.680 risk of cardiovascular disease and risk of death among people 0:48:50.680 --> 0:48:53.880 who drank coffee. Now this was strange because we know 0:48:54.120 --> 0:48:58.880 from huge, much larger and much more recent epidemiological studies 0:48:58.920 --> 0:49:03.960 that drinking coffee is protective at in terms of reducing 0:49:04.000 --> 0:49:06.920 death risk. Like that that is the case, and we 0:49:07.000 --> 0:49:09.200 don't know in terms of cause and effect or exactly 0:49:09.280 --> 0:49:11.360 what's going on. But you know, a lot more is 0:49:11.440 --> 0:49:14.600 known now than was known then. These early studies, which 0:49:14.640 --> 0:49:18.000 were done in the middle part of the twentieth century 0:49:18.560 --> 0:49:22.680 where people were still drinking boiled coffee and Scandinavia, triggered 0:49:22.719 --> 0:49:26.759 some interest in what was causing that potentially instead of 0:49:26.840 --> 0:49:29.319 just like life factors that were associated with people who 0:49:29.400 --> 0:49:31.160 drank coffee, right, So they wanted to know, is there 0:49:31.239 --> 0:49:34.600 something in this coffee that is causing higher risk of 0:49:34.880 --> 0:49:39.239 heart attack basically, and if they picked it up in 0:49:39.280 --> 0:49:42.279 the study, it was scatatistically significant. So it wasn't just 0:49:42.320 --> 0:49:44.600 like a little thing. It wasn't just a little blip 0:49:44.600 --> 0:49:47.000 in the data. It was concerning enough where they invested 0:49:47.040 --> 0:49:50.359 a lot of money in trying to figure out and 0:49:50.440 --> 0:49:53.640 time what was going on. And so in countries kind 0:49:53.640 --> 0:49:56.799 of all over they started digging into this and what 0:49:56.840 --> 0:50:00.799 they found was a set of chemical that are in 0:50:00.920 --> 0:50:06.879 coffee beans that are they have this name capistol and coweol, 0:50:07.400 --> 0:50:11.160 and they are a group of terpenoids. They're dieterping alcohols. 0:50:11.160 --> 0:50:14.799 That's the technical kind of class that they're in. And 0:50:15.320 --> 0:50:21.600 these are fat soluble very lightweight molecules that like being 0:50:21.640 --> 0:50:25.600 dissolved in things like lipids. And what they do is 0:50:25.760 --> 0:50:30.279 it turns out that that those two chemicals were probably 0:50:30.600 --> 0:50:35.600 the reason that they detected this higher cardiovascular risk in 0:50:35.640 --> 0:50:39.239 people who are drinking unfiltered coffee basically. And what they 0:50:39.320 --> 0:50:43.400 do is these two chemicals they are not themselves cholesterol. 0:50:44.360 --> 0:50:47.080 So you know, it's not like you're eating cheese or 0:50:47.160 --> 0:50:49.440 you know, you got to watch your diet because of that, because, right, 0:50:49.520 --> 0:50:53.960 our shrimp have a lot of cholesterol. No, the LDLC, 0:50:54.480 --> 0:50:56.440 which is the cholesterol that's kind of known as the 0:50:56.480 --> 0:51:00.239 bad cholesterol, although that's also a little bit of a misnumber, right, 0:51:00.560 --> 0:51:04.680 but the LDLC cholesterol is the cholesterol level that doctors 0:51:04.680 --> 0:51:07.880 are tracking, whether in when they decide to give you 0:51:07.920 --> 0:51:10.800 a statin or not. Okay, so this is the stuff 0:51:10.800 --> 0:51:14.319 that is forming plaques, that's causing athlosclerosis and that sort 0:51:14.360 --> 0:51:16.880 of thing. You know, The idea is that lower is 0:51:16.960 --> 0:51:21.480 better in terms of you know, life extension. So what 0:51:21.560 --> 0:51:24.560 they noticed was cafaestell and kawi alf. You if I 0:51:24.600 --> 0:51:27.400 gave that to you, just the same amount that you 0:51:27.440 --> 0:51:29.920 would get in say, drinking four cups of French press 0:51:29.920 --> 0:51:34.680 coffee your cholesterol levels if you hadn't been drinking French press, 0:51:34.760 --> 0:51:36.719 so I couldn't do this to you. But if you 0:51:36.760 --> 0:51:39.320 hadn't been drinking French press, you could measure the increase 0:51:39.360 --> 0:51:41.239 and you would see an increase of maybe ten to 0:51:41.239 --> 0:51:45.480 fifteen percent of the LDLC in the weeks two weeks after, 0:51:45.800 --> 0:51:49.839 you know, continuing to drink it. And so they did that. 0:51:49.920 --> 0:51:52.839 You know, they isolated these compounds. It's definitely them that's 0:51:52.880 --> 0:51:56.720 causing it, and they're filtered out by a paper filter. 0:51:57.880 --> 0:52:00.600 They're also filtered out by the formation of what's called 0:52:00.600 --> 0:52:03.680 a filter cake of the grounds of coffee themselves. Because 0:52:03.719 --> 0:52:07.800 these diterping alcohols caffistan call wee all bind to small 0:52:08.000 --> 0:52:12.239 particles in the coffee that you during the grind process, right, 0:52:12.280 --> 0:52:14.200 that are made during the grind process, and then during 0:52:14.239 --> 0:52:17.200 the brewing process. If there's not something to catch those 0:52:17.239 --> 0:52:20.560 small particles, those small particles will make it through into 0:52:20.600 --> 0:52:22.520 the brew, which of course they do in a French 0:52:22.560 --> 0:52:24.719 press because that thing you plunge through is just a 0:52:24.760 --> 0:52:27.840 really rough mesh filter, right, So it's catching some of 0:52:27.840 --> 0:52:30.000 the grounds, but you know, a lot most of the 0:52:30.040 --> 0:52:32.520 smallest particles are making the way through, which means most 0:52:32.560 --> 0:52:35.919 of the available caffistan call we all is also making 0:52:35.960 --> 0:52:38.439 it through, and the amount that's available depends on the bean. 0:52:38.680 --> 0:52:41.640 Robust and Arabica have different amounts of the caffistan callwe all. 0:52:42.360 --> 0:52:48.480 How much it's roasted has an effect, Okay, But roughly speaking, 0:52:48.520 --> 0:52:50.480 if you have an Arabica bean, it's going to have 0:52:50.640 --> 0:52:53.520 a decent amount of caffistan caullwie al in it, and 0:52:53.800 --> 0:52:56.719 if you don't filter it, you're gonna raise your cholesterol 0:52:56.800 --> 0:52:59.360 because of it. At least that's how I interpret it. 0:52:59.400 --> 0:53:01.719 All this littera and I did a deep dive, and 0:53:01.760 --> 0:53:04.760 the nutrition literature is fascinating because there are these studies 0:53:04.800 --> 0:53:07.240 where what they got to do with the graduate students 0:53:07.440 --> 0:53:10.520 was make coffee six ways from Sunday and then measure 0:53:10.560 --> 0:53:13.840 the kaffistall colwieol in it. It's just so funny. But 0:53:13.920 --> 0:53:17.600 what's clear is that an auto drip, because it's water 0:53:17.760 --> 0:53:21.680 gently kind of dripping down on the grounds, it's kind 0:53:21.680 --> 0:53:25.200 of retaining the structure of all of those grounds. Right, 0:53:25.880 --> 0:53:29.040 even though the gold mesh filter absolutely would let the 0:53:29.120 --> 0:53:32.239 diet tirping alcohols through the little poor and the mesh, right, 0:53:32.840 --> 0:53:36.640 but what's trapping them is that all of the coffee 0:53:36.640 --> 0:53:39.560 grounds themselves. And so that's why a gold mesh filter 0:53:39.680 --> 0:53:42.760 will work to filter out most of the caffistan callie 0:53:42.760 --> 0:53:45.479 all in an auto drip, but not a pore over 0:53:45.840 --> 0:53:48.200 because you're swirling the grounds around in the poor over, 0:53:48.239 --> 0:53:51.480 aren't you right? You're taking that kettle and moving them around, 0:53:51.600 --> 0:53:54.400 swirling them around, so the particles will get through the 0:53:54.400 --> 0:53:56.800 gold mesh and a pour over, but not a paper filter. 0:53:57.400 --> 0:54:02.480 So this is like I cannot believe, this is where 0:54:02.480 --> 0:54:05.080 I ended up in the book, like a lot of attention, 0:54:05.239 --> 0:54:07.040 but you know, I like going down these rabbit holes. 0:54:07.520 --> 0:54:12.279 And if you think about cholesterol levels, you know, the 0:54:12.320 --> 0:54:16.160 two most potent inducing chemicals in our diet for LDL 0:54:16.280 --> 0:54:19.719 cholesterol are these two chemicals. And the way they work 0:54:19.840 --> 0:54:23.279 is they bind to a receptor in your body that 0:54:23.400 --> 0:54:26.840 tricks your liver into making more LDL cholesterol. That is 0:54:26.840 --> 0:54:31.319 what happens. So really stepping back, thinking like if there's 0:54:31.360 --> 0:54:33.759 one public health message, you know, and I can't give 0:54:33.800 --> 0:54:36.680 it because I'm not an epidemiologist or a physician, but 0:54:36.800 --> 0:54:39.600 for myself, just for my own health, you know, this 0:54:39.760 --> 0:54:42.080 was the most salient thing and I stopped drinking French 0:54:42.080 --> 0:54:44.279 press too, and I used to only drink it. And 0:54:44.400 --> 0:54:47.800 of course LDL cholesterol levels vary a lot between people 0:54:47.800 --> 0:54:50.759 for lots of reasons, including genetics and diet. Right, not 0:54:50.920 --> 0:54:53.480 in the broadest sense, but for me, I thought, this 0:54:53.560 --> 0:54:55.560 is a simple thing I could do just to keep 0:54:55.600 --> 0:54:58.400 it down. It really depends on the person, you know, Like, 0:54:58.640 --> 0:55:01.080 I don't want to make an or arching statement about this, 0:55:01.440 --> 0:55:05.440 but the literature is clear. The scientific literature is clear 0:55:05.480 --> 0:55:08.040 about this. In my mind, it has been muddied and 0:55:08.160 --> 0:55:11.000 not well communicated, is what I would say. 0:55:12.040 --> 0:55:15.520 You ended your book with a look towards the future 0:55:15.680 --> 0:55:20.080 and the possible consequences of biodiversity loss as it relates 0:55:20.120 --> 0:55:24.000 to toxins. What are we at risk of losing as 0:55:24.040 --> 0:55:28.560 we bulldoze forests or fragment habitat or let the warming 0:55:28.719 --> 0:55:32.520 climate burn or desiccate tracts of biodiverse land. 0:55:33.520 --> 0:55:37.640 Well, the sad news is we are going to lose 0:55:37.760 --> 0:55:40.759 the future pharmacopeia, right, and not only that, we're going 0:55:40.800 --> 0:55:44.000 to lose the biodiversity that's making those things. Where the 0:55:44.000 --> 0:55:47.360 war of nature is raging at its strongest is in 0:55:47.400 --> 0:55:51.719 the tropics, and these beautiful studies that were done in 0:55:51.760 --> 0:55:55.160 the middle part of the twentieth century. This ecologist did 0:55:55.200 --> 0:55:57.920 sort of a transect, you know, sort of measuring alkaloid 0:55:58.040 --> 0:56:02.400 levels across different biomes from the poles to the equator, 0:56:02.480 --> 0:56:06.839 and then they had these controls in equatorial zones that 0:56:06.880 --> 0:56:10.080 had mountains, so there's less diversity at the tops of 0:56:10.120 --> 0:56:13.160 the mountains right than at the base and lowland tropical forests, 0:56:13.560 --> 0:56:16.759 and so that kind of mimics the latitudinal gradient that 0:56:16.880 --> 0:56:20.600 von Humboldt discovered. This mirroring by the way, in terms 0:56:20.600 --> 0:56:23.680 of species numbers and how diverse things get. They're more 0:56:23.680 --> 0:56:26.160 diverse at the equator and less diverse at the poles, 0:56:26.520 --> 0:56:29.879 more diverse in lowland tropical forests than at the upper 0:56:29.960 --> 0:56:35.440 limits of the mountains. And they saw the alkaloid diversity 0:56:35.719 --> 0:56:41.160 parallel that so plants on average produce more alkaloid diversity 0:56:41.200 --> 0:56:43.839 than in the tropics and the lowland tropics than they 0:56:43.920 --> 0:56:47.040 do at the tops of the mountains per species, and 0:56:47.120 --> 0:56:50.919 also towards the poles. And so the interpretation was that 0:56:51.040 --> 0:56:54.759 the interactions between species are stronger in the tropics and 0:56:54.840 --> 0:56:57.680 where there's more diversity, where it's warmer for a longer 0:56:57.719 --> 0:57:01.920 period of time or stable warmth basically. And so these 0:57:02.040 --> 0:57:06.480 cradles of biodiversity that harbor most species also harbor most 0:57:06.520 --> 0:57:10.319 of the toxins, most of the chemical diversity that we 0:57:10.760 --> 0:57:12.960 have on the planet that have access to now and 0:57:13.000 --> 0:57:17.840 in the future, and so and those lands are largely 0:57:18.360 --> 0:57:21.880 controlled by indigenous people, who are also the most endangered 0:57:22.040 --> 0:57:24.280 you know, cultures in the world in terms of their 0:57:25.200 --> 0:57:28.680 just their being right and their languages, their cultures, all 0:57:28.720 --> 0:57:32.760 of that, they're the least empowered. And so the other 0:57:32.800 --> 0:57:35.200 thing that's interesting, just as a general rule, not just 0:57:35.240 --> 0:57:38.800 in the tropics, but indigenous lands hold maybe fifty percent 0:57:38.840 --> 0:57:43.560 of the carbon sequestering capacity of the terrestrial realm. And 0:57:43.640 --> 0:57:46.240 so I didn't think I'd end up here, but it 0:57:46.320 --> 0:57:49.640 was sort of like forget about the pharmacopeia, just thinking about, 0:57:49.920 --> 0:57:52.440 you know, the future of the planet is really in 0:57:52.480 --> 0:57:55.880 the hands of indigenous people and empowering them. And if 0:57:55.880 --> 0:57:58.120 we do that, so many things get solved, Like their 0:57:58.400 --> 0:58:03.120 existence is fortify right, their rights are guaranteed, and then 0:58:03.320 --> 0:58:05.480 the rest kind of hitches along for the ride, is 0:58:05.800 --> 0:58:08.920 what I would say. So human rights kind of becomes 0:58:09.040 --> 0:58:10.720 like the focus of the book at the end, but 0:58:11.160 --> 0:58:13.040 you know, it's sort of like, yeah, the other stuff 0:58:13.080 --> 0:58:16.680 is sort of just tagging along. But you know, the 0:58:16.720 --> 0:58:19.360 future pharmacopeia for our descendants is going to be there 0:58:19.400 --> 0:58:21.920 in the tropics. Yes they're drugs. New drugs will come 0:58:21.960 --> 0:58:24.600 out of the temperate zones too, but most of them 0:58:24.680 --> 0:58:26.640 are going to come out of the tropics still, you know, 0:58:26.680 --> 0:58:30.520 for natural drugs, and yes, synthetic drugs with AI and all, 0:58:30.560 --> 0:58:34.840 this definitely very promising. You know, directed evolution, there's all 0:58:34.920 --> 0:58:38.040 kinds of new ways of thinking about making synthetic drugs 0:58:38.080 --> 0:58:40.840 and that's going to be very important. But on the 0:58:40.840 --> 0:58:44.400 other hand, if you just look at the approved cancer 0:58:44.480 --> 0:58:47.840 drugs anti cancer drugs, more than half are from plants, 0:58:48.520 --> 0:58:53.560 so that that's still true, and so there's untapped potential. 0:58:53.600 --> 0:58:56.120 People's lives have been saved by tax all I guarantee 0:58:56.160 --> 0:58:59.000 you of some of your listeners. So this really hits 0:58:59.000 --> 0:59:01.840 home for people when you think about that, right, think 0:59:01.880 --> 0:59:05.400 about the next tax all that is somewhere in the 0:59:05.400 --> 0:59:09.040 Atlantic forest in Brazil and some tree that exists in 0:59:09.080 --> 0:59:12.760 a tiny population, is it going to be there? You know? 0:59:12.920 --> 0:59:15.200 And that's the thing. It's like, this is this is 0:59:15.200 --> 0:59:18.720 something that we can control that we have the we 0:59:19.480 --> 0:59:21.520 have right. The fate is in our hands. 0:59:40.920 --> 0:59:43.880 Doctor Whiteman, thank you so very much for taking the 0:59:43.920 --> 0:59:46.400 time to chat with me. Honestly, I feel like we 0:59:46.520 --> 0:59:49.720 could have talked about poisons all day and I would 0:59:49.720 --> 0:59:52.120 have loved it. For any of you out there that 0:59:52.160 --> 0:59:54.960 feels the same way and wants to learn even more 0:59:55.040 --> 0:59:58.520 about toxins, check out our website this podcast will Kill 0:59:58.560 --> 1:00:00.840 You dot com, where I'll post link to where you 1:00:00.880 --> 1:00:04.040 can find most dangerous poison, as well as a link 1:00:04.080 --> 1:00:07.600 to doctor Whiteman's lab website. 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