For the Notes see below or click here for 270 page downloadable PDF. There are 2083 reference numbers, but these do not always cite unique references, some are repeated.
Introduction
Page 3. As sixteenth-century Swiss physician. Philippus Theophrastus Aureolus Bombastus von Hohenheim (1493-1541), later known as Paracelsus, was a founder of the field of toxicology. The maxim “the dose makes the poison” paraphrases what Paracelsus wrote in German: “Alle Dinge sind Gift, und nichts ist ohne Gift; allein die dosis machts, daß ein Ding kein Gift sei.“ This is translated into English as: “All things are poison and nothing is without poison; only the dose makes it so that a thing is not a poison.”
1. Paracelus, Theophrastus. “Die dritte Defension wegen des Schreibens der neuen Rezepte.” In Septem Defensiones 1538. Werke Bd. 2, Darmstadt 1965, S. 510. Accessed June 19, 2023: http://www.zeno.org/nid/20009261362.
Page 3. At the wrong dose. Atmospheric oxygen can become toxic at partial pressures higher than those at sea level. Excess reactive oxygen species like superoxide radicals may overwhelm antioxidant buffering mechanisms and damage biomolecules prone to oxidation, such as lipids.
2. Fridovich, I. (1998). “Oxygen Toxicity: A Radical Explanation.” Journal of Experimental Biology, 201(8), 1203–1209. https://doi.org/10.1242/jeb.201.8.1203
Page 4. The chemicals that I call toxins. The “war of nature” quote is from page 490 of the first British edition of the book that became known as The Origin of Species by Charles Darwin, who wrote: “Thus, from the war of nature, from famine and death, the most exalted object which we are capable of conceiving, namely, the production of the higher animals, directly follows.” Darwin mused about how. The “entangled bank” quote is from page 489.
3. Darwin, C. (1859). On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. London: Murray (1st edition). Accessed June 19, 2023: http://darwin-online.org.uk/Variorum/1859/1859-490-c-1860.html.
Page 7. It often hosts more great gray owls. The Sax-Zim Bog supports many great gray owl (Strix nebulosa) individuals during irruption years when microtine rodent populations wane in more northerly regions.
4. Svingen, P.H. and Lind, J.W. (2005). “The 2004–2005 influx of northern owls part II: Great gray owl.” The Loon 77: 194–208. Accessed June 19, 2023: https://www.moumn.org/loon/pdf/2005.pdf#page=194.
Page 8. The local school. The Toivola-Meadowlands School was initially closed by Independent School District #710 in 1992 owing to decreasing enrollment and then briefly operated as a charter school before permanently closing in 1998. Noah Whiteman received his high school diploma from the charter school in 1994.
5. Whiteman, N. 2023. Personal observation.
Chapter 1. Deadly Daisies
Page 9. Within the infant rind. This quote is from Act 2, Scene 3 from William Shakespeare’s Romeo and Juliet. Friar Laurence carries a basket containing medicinal herbs that hold both the power to cure and the power to harm.
6. Shakespeare, W. (1594). The Tragedy of Romeo and Juliet. Open Source Shakespeare. George Mason University. Accessed June 20, 2023: https://www.opensourceshakespeare.org.
Page 9. Even in its “infant rind,” the mum. Matricin, also known as matricine, is a sesquiterpene lactone chemical produced by Asteraceae. In the acidic environment of the human stomach, matricin is converted into chamazulene carboxylic acid, which decarboxylates into chamazulene. Chamazulene carboxylic acid and chamazulene are hypothesized to have anti-inflammatory effects with modes of action similar to synthetic non-steroidal anti-inflammatory drugs (NSAID) ibuprofen and naproxen. This is likely due to the structural similarities between chamazulene carboxylic acid, chamazulene and NSAIDs, which inhibit proinflammatory enzymes. Chamazulene was the most abundant terpenoid released by the mountain yarrow Achillea collina after aphid infestation, implicating its role as an anti-herbivore defense.
7. Ramadan, M., Goeters, S., Watzer, B., Krause, E., Lohmann, K., Bauer, R., Hempel, B., & Imming, P. (2006). “Chamazulene Carboxylic Acid and Matricin: A Natural Profen and Its Natural Prodrug, Identified through Similarity to Synthetic Drug Substances.” Journal of Natural Products, 69(7), 1041–1045. https://doi.org/10.1021/np0601556
8. Safayhi, H., Sabieraj, J., Sailer, E. -R., and H. P. T. Ammon. (1994). “Chamazulene: An antioxidant-type inhibitor of leukotriene B4 formation.” Planta Medica 60: 410–413. https://doi.org/10.1055/s-2006-959520.
9. Giorgi, A., Panseri, S., Nanayakkarawasam, N., N. M. C., Chiesa, L. M. (2012). “HS-SPME-GC/MS analysis of the volatile compounds of Achillea collina: Evaluation of the emissions fingerprint induced by Myzus persicae infestation.” Journal of Plant Biology 55: 251–260. https://doi.org/10.1007/s12374-011-0356-0.
Page 9. The eastern white pine held its own piperidine alkaloids. Piperidine is a heterocyclic amine (see Appendix) naturally produced by plants like those in the genus Piper. Piperidine was discovered in the 19th century when piperine was treated with nitric acid in the laboratory. Piperine and an isomer of piperine called chavicine are the predominant molecules that drive the peppery taste of black pepper (Piper nigrum). The piperidine ring is also used as the foundation for synthetic drugs, including fentanyl. Piperidine alkaloids are found in many species of spruce, fir, and pine, including the eastern white pine (Pinus strobus), which produces pinidine. These chemicals are also made by distantly related plants, such as poison hemlock (Conium maculatum), which produces the highly toxic piperidine alkaloid coiinne, and by pitcher plants (Sarracenia spp.), which ostensibly paralyzes the insects that fall into the pitcher. Coiinine and related alkaloids in poison hemlock may have killed Socrates. Insects also synthesize piperidine alkaloids, including fire ants (Solenopsis spp.), which produce solenopsins that are venom components, and coccinellid beetles, which produce other piperidines that are secreted in defensive glands or during reflex bleeding. Piperidine alkaloids thus play a defensive role against natural enemies of both the plants and insects that synthesize these chemicals.
11. Veličkovic′, D., Liao, H.-L., Vilgalys, R., Chu, R. K., and Anderton, C. R. (2019). “Spatiotemporal transformation in the alkaloid profile of Pinus roots in response to mycorrhization.” Journal of Natural Products 82: 1382–1386. Accessed June 22, 2023: https://pubs.acs.org/doi/full/10.1021/acs.jnatprod.8b01050.
14. Tawara, J. N., A. Blokhin, T. A. Foderaro, and F. R. Sermitz. (1993). “Toxic piperidine alkaloids from pine (Pinus) and spruce (Picea) trees. New structures and a biosynthetic hypothesis.” Journal of Organic Chemistry 58: 4813–4818. Accessed June 22, 2023: https://pubs.acs.org/doi/abs/10.1021/jo00070a014
15. Mody, V., Henson, R., Hedin, P. A., Kokpol, U., and D. H. Miles. (1976). “Isolation of the insect paralyzing agent coniine from Sarracenia flava.” Experientia 32: 829–830. Accessed June 22, 2023: https://link.springer.com/article/10.1007/BF02003710
16. Shtykova, L., Masuda, M., Eriksson, C., Sjödin, K., Marling, E., Schlyter, F., & Nydén, M. (2008). Latex coatings containing antifeedants: Formulation, characterization, and application for protection of conifer seedlings against pine weevil feeding. Progress in Organic Coatings, 63(2), 160–166. https://doi.org/10.1016/j.porgcoat.2008.05.006 Page 9. St. John’s wort contains the phenolic compound hypericin. St. John’s Wort produces the anthraquinone derivative hypericin, which has a large chromophore structure (see Appendix) that absorbs visible light in the 590 nm range. Upon digestion, hypericin moves through the blood to the skin and can be toxic owing to the production of singlet oxygen, which is highly reactive with biomolecules. Hypericin is a toxin to herbivorous insects as well as livestock and other domestic animals that feed on this plant can be injured owing to photosensitivity. The plant is also widely used medicinally.
17. Volmer, J.J. and Rosenson J. (2004). “Chemistry of St. John’s Wort: Hypericin and Hyperforin.” Journal of Chemical Education 81: 1450–1465. Accessed June 22, 2023: https://pubs.acs.org/doi/pdf/10.1021/ed081p1450
20. Samuels, R., Knox, P. (1989). “Insecticidal activity of hypericin towards Manduca sexta larvae.” Journal of Chemical Ecology 15: 855–862. Accessed June 22, 2023: https://link.springer.com/article/10.1007/BF01015181
Page 9. and sea holly, the aldehyde eryngial. The sea holly (Eryngium maritimum), a member of the dill family (Apiaceae) produces the aldehyde eryngial, also called trans-2-dodecenal (see Appendix). Other members of the dill family such as cilantro (coriander; Coriandrum sativum), ginger (Zingiber officionale), citrus (orange peel; Citrus x sinensis) also produce this compound, as do some Rhinocricus millipedes. Sea holly has been used as a medicinal for a variety of ailments.
21. Forbes, W. M., Gallimore, W. A., Mansingh, A., Reese, P. B., & Robinson, R. D. (2014). Eryngial ( trans -2-dodecenal), a bioactive compound from Eryngium foetidum : its identification, chemical isolation, characterization and comparison with ivermectin in vitro. Parasitology, 141(2), 269–278. https://doi.org/10.1017/S003118201300156X
22. Manville, R. W., & Abbott, G. W. (2019). Cilantro leaf harbors a potent potassium channel–activating anticonvulsant. The FASEB Journal, 33(10), 11349–11363. https://doi.org/10.1096/fj.201900485R
23. Wheeler, J. W., Meinwald, J., Hurst, J. J., & Eisner, T. (1964). trans -2-Dodecenal and 2-Methyl-1,4-Quinone Produced by a Millipede. Science, 144(3618), 540–541. https://doi.org/10.1126/science.144.3618.540
Page 10. The needles of eastern white pine have long been used. This species (Pinus strobus) and many others in the genus Pinus have been used by Indigenous peoples of North America as medicinals to treat a variety of conditions, from dermatological to respiratory. An example is given below, but also see
24. Rousseau, J., (1947). “Ethnobotanique Abenakise.” Archives de Folklore 11: 145–182. Accessed June 22, 2023. Found by searching “Pinus strobus via http://naeb.brit.org/uses/species/2977.
26. Flood, M., & Myhal, N. (2022). White Pine in Time and Place. History of Pharmacy and Pharmaceuticals, 63(2), 302–327. https://doi.org/10.3368/hopp.63.2.302. Page 10. Hypericin in St. John’s wort is widely used. 27. Linde, K., Ramirez, G., Mulrow, C. D., Pauls, A., Weidenhammer, W., & Melchart, D. (1996). St John’s wort for depression--an overview and meta-analysis of randomised clinical trials. BMJ, 313(7052), 253–258. https://doi.org/10.1136/bmj.313.7052.253
28. Nahrstedt, A., & Butterweck, V. (2010). Lessons Learned from Herbal Medicinal Products: The Example of St. John’s Wort. Journal of Natural Products, 73(5), 1015–1021. https://doi.org/10.1021/np1000329
Page 10. Finally, Jamaican scientists.
29. Forbes, W. M., Gallimore, W. A., Mansingh, A., Reese, P. B., & Robinson, R. D. (2014). Eryngial ( trans -2-dodecenal), a bioactive compound from Eryngium foetidum : its identification, chemical isolation, characterization and comparison with ivermectin in vitro. Parasitology, 141(2), 269–278. https://doi.org/10.1017/S003118201300156X
Page 10. One big hint came.
30. Manville, R. W., & Abbott, G. W. (2019). Cilantro leaf harbors a potent potassium channel–activating anticonvulsant. The FASEB Journal, 33(10), 11349–11363. https://doi.org/10.1096/fj.201900485R
Page 12. We scattered his ashes. The quote “shining Big-Sea-Water” of Lake Superior” is from Henry Wadsworth Longfellow’s 1855 poem The Song of HiawathaIII. Hiawatha’s Childhood. Accessessed June 23, 2023: https://www.hwlongfellow.org/poems_poem.php?pid=277. The relevant excerpt is here:
By the shores of Gitche Gumee, By the shining Big-Sea-Water, Stood the wigwam of Nokomis, Daughter of the Moon, Nokomis. Dark behind it rose the forest, Rose the black and gloomy pine-trees, Rose the firs with cones upon them; Bright before it beat the water, Beat the clear and sunny water, Beat the shining Big-Sea-Water.
Page 13. The two outermost pieces are of black walnut. Juglone (5-hydroxy-1,4-naphthoquinone) is produced by walnut trees and when it leaches into the soil, can inhibit the growth of other plants. Juglone is an isomer of lawson (2-hydroxy-1,4-naphthoquinone), which is the red-staining dye in henna.
31. Cook, M.T. (1921). “Wilting caused by walnut trees.” Phytopathology 11: 346. Not available online.
32. Willis, R. J. (2000). “Juglans spp., juglone and allelopathy.” Allelopathy Journal 7: 1–55. Accessed June 23, 2023: https://www.allelopathyjournal.com/Journal_Articles/AJ%207%20(1)%20January,%202000%20(1-55).pdf. Page 14. In the Achilleid, first-century. The origins of the imperfect vulnerability motif involving Thetis and her son Achilles from 33. Harrauer, C. (2010). “Why Styx? Some remarks on Satius’s Achilleid.” Wiener Studien 123: 167–175. Accessed June 23, 2023: https://www.jstor.org/stable/24752330. Page 14. As our own lineage. 34. Bramble, D. M., & Lieberman, D. E. (2004). Endurance running and the evolution of Homo. Nature, 432(7015), 345–352. https://doi.org/10.1038/nature03052
35. Gibbons, A. (2013). “Human evolution: Gain came with pain blame your bad back and sprained ankle on an imperfect reworking of the ape body plan.” Science. doi: 10.1126/article.26387. Accessed June 24, 2023: https://www.science.org/content/article/human-evolution-gain-came-pain
Page 16. Pyrethrum powder was first. The first reference below has been translated into English online (if the website is visited the journal gives one the option of German or English). The second reference is an excellent history and detailed account of the use of pyrethrum powder over time.
36. Roth, K., & Vaupel, E. (2017). Von Insekten, Chrysanthemen und Menschen. Chemie in Unserer Zeit, 51(3), 162–184. https://doi.org/10.1002/ciuz.201700786
Page 17. Chrysanthemums have been. The role of Japanese scientists in particular is surveyed in the reference below.
38. Matsuo, N. (2019). “Discovery and development of pyrethroid insecticides. Proceedings of the Japan Academy.” Series B, Physical and Biological Sciences. 95: 378–400. Accessed June 24, 2023: https://doi.org/10.2183/pjab.95.027.
Page 18. This physiological reaction sounds bad. A few examples of the off-target effects of natural and synthetic pyrethrins.
39. Antwi, F. B., & Reddy, G. V. P. (2015). Toxicological effects of pyrethroids on non-target aquatic insects. Environmental Toxicology and Pharmacology, 40(3), 915–923. https://doi.org/10.1016/j.etap.2015.09.023
40. Haya, K. (1989). Toxicity of pyrethroid insecticides to fish. Environmental Toxicology and Chemistry, 8(5), 381–391. https://doi.org/10.1002/etc.5620080504
Page 18. Dose for dose.
41. Roth, K., & Vaupel, E. (2017). Von Insekten, Chrysanthemen und Menschen. Chemie in Unserer Zeit, 51(3), 162–184. https://doi.org/10.1002/ciuz.201700786
Page 18. For example, a single. Although this article focused on the rat, the authors changed one amino acid in one of the rat’s voltage gated sodium channels to mimic the insect version and found that that one amino acid change can explain the high susceptibility of arthropods, including insects, to pyrethrins.
42. Vais, H., Atkinson, S., Eldursi, N., Devonshire, A. L., Williamson, M. S., & Usherwood, P. N. R. (2000). A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides. FEBS Letters, 470(2), 135–138. https://doi.org/10.1016/S0014-5793(00)01305-3
Page 18. By contrast, cats. Cats are missing an enzyme necessary for the detoxification of pyrethrins.
43. Boland, L. A., & Angles, J. M. (2010). Feline permethrin toxicity: Retrospective study of 42 cases. Journal of Feline Medicine and Surgery, 12(2), 61–71. https://doi.org/10.1016/j.jfms.2009.09.018
Page 18. Consider the sad story. Although there are apocryphal stories of newts poisoning people in a variety of contexts, the below is a true story involving a dare gone wrong.
44. Bradley, S. G., & Klika, L. J. (1981). A Fatal Poisoning From the Oregon Rough-Skinned Newt (Taricha granulosa). JAMA: The Journal of the American Medical Association, 246(3), 247. https://doi.org/10.1001/jama.1981.03320030039026
Page 18. Although pyrethrins are made by plants, tetrodotoxin.
45. Tani, T. (1945). Nihonsan Fugu no Chudokugakuteki Kenkyu (Toxicological Studies on Japanese Puffer). Tokyo, Teikokutosho, 1945, 15-27.
46. Yokoo, A. (1950). Study on chemical purification of tetrodotoxin (3)-purification of spheroidine. Journal of the Chemical Society of Japan, 71(11), 590-592.
47. Mosher, H. S., Fuhrman, F. A., Buchwald, H. D., & Fischer, H. G. (1964). Tarichatoxin—Tetrodotoxin: A Potent Neurotoxin. Science, 144(3622), 1100–1110. https://doi.org/10.1126/science.144.3622.1100
48. Sheumack, D. D., Howden, M. E. H., Spence, I., & Quinn, R. J. (1978). Maculotoxin: A Neurotoxin from the Venom Glands of the Octopus Hapalochlaena maculosa Identified as Tetrodotoxin. Science, 199(4325), 188–189. https://doi.org/10.1126/science.619451
49. Chau, R., Kalaitzis, J. A., & Neilan, B. A. (2011). On the origins and biosynthesis of tetrodotoxin. Aquatic Toxicology, 104(1–2), 61–72. https://doi.org/10.1016/j.aquatox.2011.04.001
Page 18. There is nothing inherently healthy about natural products.
50. Meier, B. P., Dillard, A. J., & Lappas, C. M. (2019). Naturally better? A review of the natural‐is‐better bias. Social and Personality Psychology Compass, 13(8). https://doi.org/10.1111/spc3.12494
Page 19. Darwin remarked that the birds. Quote “a gun here is almost superfluous; for with the muzzle of one I pushed a hawk off the branch of a tree”from reference below, also known as The Voyage of the Beagle.
51. Darwin, C. 1890. Journal of researches into the natural history and geology of the various countries visited by H.M.S. Beagle etc. (First Murray illustrated ed.), London: John Murray.
Page 20. One of the largest in the world.
52. Clark, D. B. (1979). A Centipede Preying on a Nestling Rice Rat (Oryzomys bauri). Journal of Mammalogy, 60(3), 654–654. https://doi.org/10.2307/1380119
53. Ortiz-Catedral, L., Christian, E., Chimborazo, W., Sevilla, C., & Rueda, D. (2021). A Galapagos centipede Scolopendra galapagoensis preys on a Floreana Racer Pseudalsophis biserialis. Galapagos Research, 70, 2-4.
54. Menezes, J. C. T., & Marini, M. Â. (2017). Predators of bird nests in the Neotropics: a review. Journal of Field Ornithology, 88(2), 99–114. https://doi.org/10.1111/jofo.12203
56. Price, R. D., & Beer, J. R. (1963). Species of Colpocephalum (Mallophaga: Menoponidae) Parasitic upon the Falconiformes. The Canadian Entomologist, 95(7), 731–763. https://doi.org/10.4039/Ent95731-7
Page 20. I wanted to use mutations.
57. Whiteman, N. K., & Parker, P. G. (2005). Using parasites to infer host population history: a new rationale for parasite conservation. Animal Conservation, 8(2), 175–181. https://doi.org/10.1017/S1367943005001915
Page 20. It was likely that each hawk.
58. Koop, J. A. H., DeMatteo, K. E., Parker, P. G., & Whiteman, N. K. (2014). Birds are islands for parasites. Biology Letters, 10(8), 20140255. https://doi.org/10.1098/rsbl.2014.0255
Page 21. The first hawk that I “dust ruffled.”
59. Clayton, D. H. and Drown D. M. (2001). Critical evaluation of five methods for quantifying chewing lice (Insecta: Phthiraptera). Journal of Parasitology 87: 1291–1300. Accessed June 26, 2023: https://doi.org/10.1645/0022-3395(2001)087[1291:CEOFMF]2.0.CO;2.
Page 21. Through our research.
60. Whiteman, N. K., Kimball, R. T., & Parker, P. G. (2007). Co-phylogeography and comparative population genetics of the threatened Galápagos hawk and three ectoparasite species: ecology shapes population histories within parasite communities. Molecular Ecology, 16(22), 4759–4773. https://doi.org/10.1111/j.1365-294X.2007.03512.x
Page 21. The mangrove finch.
61. Fessl, B., Young, G. H., Young, R. P., Rodríguez-Matamoros, J., Dvorak, M., Tebbich, S., & Fa, J. E. (2010). How to save the rarest Darwin’s finch from extinction: the mangrove finch on Isabela Island. Philosophical Transactions of the Royal Society B: Biological Sciences, 365(1543), 1019–1030. https://doi.org/10.1098/rstb.2009.0288
Page 21. It is being ravaged.
62. O’Connor, J. A., Sulloway, F. J., Robertson, J., & Kleindorfer, S. (2010). Philornis downsi parasitism is the primary cause of nestling mortality in the critically endangered Darwin’s medium tree finch (Camarhynchus pauper). Biodiversity and Conservation, 19(3), 853–866. https://doi.org/10.1007/s10531-009-9740-1
Page 21. To control these awful flies.
63. Causton, C. E. & Lincango, M. P. (2014). Review of chemical control methods for use against Philornis downsi in nests of threatened Galapagos birds, with an in-depth nontarget risk assessment of permethrin. Technical report No 1-2014. Charles Darwin Foundation for the Galapagos Islands. ISSN: 1390-6526.
64. Tebbich, S., Cimadon, A., Cunninghame, F., Anchundia, D., Causton, C., and Fessl, B. (2019). Protocolo para la aplicación de insecticidas en la base de nidos de aves terrestres amenazadas en Galápagos. Informe Tecnico No. 03 2019. Charles Darwin Foundation, Galapagos, Ecuador. Not available online.
Page 21. Cleverly, ecologist Sarah Knutie.
65. Knutie, S. A., McNew, S. M., Bartlow, A. W., Vargas, D. A., & Clayton, D. H. (2014). Darwin’s finches combat introduced nest parasites with fumigated cotton. Current Biology, 24(9), R355–R356. https://doi.org/10.1016/j.cub.2014.03.058
Page 22. Russet sparrows in China gather the leaves of wormwood.
66. Yang, C., Ye, P., Huo, J., Møller, A. P., Liang, W., & Feeney, W. E. (2020). Sparrows use a medicinal herb to defend against parasites and increase offspring condition. Current Biology, 30(23), R1411–R1412. https://doi.org/10.1016/j.cub.2020.10.021
Page 23. In fact, those first used by Indigenous healers have yielded nearly 50% of all modern drugs. This is primarily based on the World Health Organization’s estimate of 40% (Ref. 67). However, it is not clear how that 40% figure was calculated. I found that it is possible to arrive at a figure near this independently, considering two elements. The first element is the proportion of modern drugs in the strict sense (e.g., those prepared by the pharmaceutical industry and/or clinical settings) that are from natural products or inspired from them (e.g., mimics, use a natural product as a core, etc.), and the second is the proportion of these drugs that are derived from Indigenous knowledge/traditional healing practices in the broadest sense (e.,g., traditional medicine henceforth). I provide information on each element below, which gives me confidence that the nearly 50% of all modern drugs claim is reasonable.
Percent of modern drugs from nature or inspired by it: This quote, by authors of a quantitative review of the literature speaks for itself (Ref. 68): “By 1990, about 80% of drugs were either natural products or analogs inspired by them. Antibiotics (e.g., penicillin, tetracycline, erythromycin), antiparasitics (e.g., avermectin), antimalarials (e.g., quinine, artemisinin), lipid control agents (e.g., lovastatin and analogs), immunosuppressants for organ transplants (e.g., cyclosporine, rapamycins) and anticancer drugs (e.g., taxol, doxorubicin) revolutionized medicine.” A slightly lower figure for natural product-derived drugs as a percentage of the total is given for 1993, when over 50% of all drugs used in clinical settings were still derived from natural products or inspired by them (Ref. 69). Similar estimates were arrived at by others (e.g,. Ref. 70). This figure of ~50% remained the same (Ref. 71) for new drugs as well: of 1881 total drugs approved by the Food and Drug Administration (FDA) and similar entities (from 1981-2019) at least 921 (49.44%) were derived from natural products or inspired by them--the “at least” is because this figure does not include “biological macromolecules” that were also approved, which would include proteins or peptides derived originally from natural sources (e.g., components of cone snail venom, snake venom, leech saliva, etc.). Just for cancer drugs alone since 1981, of 185 new small molecules approved for cancer treatment, 120, or 64.9% were derived from natural products or inspired by them (Ref. 71).
In summary, for new drugs (from 1981-2019), the estimate of those coming from nature or inspired by those molecules is likely at least 50%, assuming some of the “biological macromolecules” are of natural origin but created through recombinant technology. Coupled with older estimates (e.g,. Ref. 69 as an example), the 50% figure for modern drugs being of natural product origin or inspired by them, seems quite reasonable and conservative.
Percent of drugs from natural products or those inspired by them that emerged from traditional medicine sensu lato: In Ref. 72, Fabricant and Farnsworth (2001) cleverly sought (there are many other similar studies as well) to determine what proportion of drugs used in modern medicine were also found in medicinal plants (which doesn’t include fungi, animals, bacteria, etc.) that were deployed in traditional medicine:
“We were requested by the WHO Traditional Medicine Programme (TRM) several years ago to provide evidence that ethnomedical information did indeed lead to useful drug discovery. We sent letters to the WHO–TRM centers throughout the world asking for their assistance in identifying all plant-derived pure compounds used as drugs in their respective countries. In addition, we surveyed pharmacopoeias of developed and developing countries to identify all such useful drugs. Next we surveyed the scientific literature to find the original papers reporting isolation of these compounds from their respective plants. This was done to determine whether the chemical efforts were stimulated by ethnomedical claims and to correlate current uses for the compounds with such ethnomedical claims (2).”
In other words, the question was whether plant-derived modern drugs were already found in the pharmacopeias of traditional knowledge-holders. The idea is that this is a highly non-random association between a plant used in traditional medicine and the fact that a modern drug exists derived from that plant or inspired by a molecule in it, likely owing to the use of that plant by the traditional healers in the first instance. The answer was that of 122 plant-derived pure compounds identified by Fabricant and Farnsworth used as drugs by physicians around the world, 80% were found in plants used by traditional healers. Flowing from this, we can deduce that if ~50% of modern drugs are from natural products or inspired by them, and that this has remained true for decades, the vast majority of medicines were derived from plants and other organisms used by traditional healers. The critical assumption is that the reason these plants and other organisms were the focus of study by modern medicine was due to the knowledge from traditional healers that was transmitted to practitioners of science in the modern sense, and then folded into the industrialized pharmacopeia. This isn’t to say there is necessarily a great fit between what ailments the traditional healers targeted with a particular plant (or other organism or concoction, etc.) and the ultimate drug and target developed by the pharmaceutical industry. Still, if we accept that ~50% of modern drugs from natural sources or inspired by them is conservative, and that the vast majority of those drugs are likely to be found in traditional medicines already, it is reasonable for WHO to claim that over 40% of modern drugs are derived from traditional medicines. Thus, the statement that “nearly 50% of all modern drugs” having been brought to light through the wisdom of Indigenous knowledge is reasonable.
67. Quote from WHO Global Centre for Traditional Medicine: “Over 40% of pharmaceutical formulations are based on natural products and landmark drugs, including aspirin and artemisinin, originated from traditional medicine.” Accessed June 27, 2023: https://www.who.int/initiatives/who-global-centre-for-traditional-medicine
68. Li, J. W.-H., & Vederas, J. C. (2009). Drug Discovery and Natural Products: End of an Era or an Endless Frontier? Science, 325(5937), 161–165. https://doi.org/10.1126/science.1168243
69. Balandrin, M. F., Kinghorn, A. D., & Farnsworth, N. R. (1993). Plant-Derived Natural Products in Drug Discovery and Development. In Human Medicinal Agents from Plants (Vol. 534, pp. 2–12). American Chemical Society. https://doi.org/doi:10.1021/bk-1993-0534.ch001
70. “In addition, 61% of all new chemical entities introduced worldwide as drugs during the same period could be traced to or were inspired by natural products.” From: Newman, D. J., Cragg, G. M., & Snader, K. M. (2003). Natural Products as Sources of New Drugs over the Period 1981−2002. Journal of Natural Products, 66(7), 1022–1037. https://doi.org/10.1021/np030096l
71. Newman, D. J., & Cragg, G. M. (2020). Natural Products as Sources of New Drugs over the Nearly Four Decades from 01/1981 to 09/2019. Journal of Natural Products, 83(3), 770–803. https://doi.org/10.1021/acs.jnatprod.9b01285
72. Fabricant, D. S., & Farnsworth, N. R. (2001). The value of plants used in traditional medicine for drug discovery. Environmental Health Perspectives, 109(suppl 1), 69–75. https://doi.org/10.1289/ehp.01109s169
Page 23. Self-medication in the animal world, or zoopharmacogosy.
73. Rodriguez, E., & Wrangham, R. (1993). Zoopharmacognosy: The Use of Medicinal Plants by Animals. In Phytochemical Potential of Tropical Plants (pp. 89–105). Springer US. https://doi.org/10.1007/978-1-4899-1783-6_4
75. Jaeger, E. C. (1944). A Source-book of Biological Names and Terms (2nd ed.). Charles C. Thomas, Springfield, IL.
76. Applequist, W. L., & Moerman, D. E. (2011). Yarrow (Achillea millefolium L.): A Neglected Panacea? A Review of Ethnobotany, Bioactivity, and Biomedical Research1. Economic Botany, 65(2), 209–225. https://doi.org/10.1007/s12231-011-9154-3
77. Dioscorides P. Osbaldeston T. A. & Wood R. P. A. (2000). De materia medica : A new indexed version in modern English. Pp. 927. Ibidis Press, Johannesburg. ISBN 0-62023435. Page 23. In addition to expounding.
78. Culpeper, N. (1995). Culpeper's Complete Herbal: A Book of Natural Remedies of Ancient Ills (The Wordsworth Collection Reference Library). NTC/Contemporary Publishing Company. ISBN 1-85326-345-1.
Page 23. Yarrow, chamomile and other daisies like wormwood.
80. Culpeper, N. (1995). Culpeper's Complete Herbal: A Book of Natural Remedies of Ancient Ills (The Wordsworth Collection Reference Library). NTC/Contemporary Publishing Company. ISBN 1-85326-345-1.
81. Tu, Y. (2011). The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine. Nature Medicine, 17(10), 1217–1220. https://doi.org/10.1038/nm.2471
Page 24. Amazingly, Neanderthals live on in.
82. Green, R. E., Krause, J., Briggs, A. W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M. H.-Y., Hansen, N. F., Durand, E. Y., Malaspinas, A.-S., Jensen, J. D., Marques-Bonet, T., Alkan, C., Prüfer, K., Meyer, M., Burbano, H. A., … Pääbo, S. (2010). A Draft Sequence of the Neandertal Genome. Science, 328(5979), 710–722. https://doi.org/10.1126/science.1188021
Page 25. The more ancient.
83. Green, R. E., Krause, J., Briggs, A. W., Maricic, T., Stenzel, U., Kircher, M., Patterson, N., Li, H., Zhai, W., Fritz, M. H.-Y., Hansen, N. F., Durand, E. Y., Malaspinas, A.-S., Jensen, J. D., Marques-Bonet, T., Alkan, C., Prüfer, K., Meyer, M., Burbano, H. A., … Pääbo, S. (2010). A Draft Sequence of the Neandertal Genome. Science, 328(5979), 710–722. https://doi.org/10.1126/science.1188021
Page 25. In addition to their DNA.
84. Hoffmann, D. L., Standish, C. D., García-Diez, M., Pettitt, P. B., Milton, J. A., Zilhão, J., Alcolea-González, J. J., Cantalejo-Duarte, P., Collado, H., de Balbín, R., Lorblanchet, M., Ramos-Muñoz, J., Weniger, G.-Ch., & Pike, A. W. G. (2018). U-Th dating of carbonate crusts reveals Neandertal origin of Iberian cave art. Science, 359(6378), 912–915. https://doi.org/10.1126/science.aap7778
Page 25. Based on their cranial sizes.
85. Holloway, R. L. (1981). Volumetric and asymmetry determinations on recent hominid endocasts: Spy I and II, Djebel Ihroud I, and the salè Homo erectus specimens, with some notes on neandertal brain size. American Journal of Physical Anthropology, 55(3), 385–393. https://doi.org/10.1002/ajpa.1330550312
Page 25. Neanderthals also probably share our ability.
86. Lalueza-Fox, C., Gigli, E., de la Rasilla, M., Fortea, J., & Rosas, A. (2009). Bitter taste perception in Neanderthals through the analysis of the TAS2R38 gene. Biology Letters, 5(6), 809–811. https://doi.org/10.1098/rsbl.2009.0532
Page 25. People vary.
87. Fox, A. L. (1932). The Relationship between Chemical Constitution and Taste. Proceedings of the National Academy of Sciences, 18(1), 115–120. https://doi.org/10.1073/pnas.18.1.115
89. Reddy, B. M., Rao, D. C., & MacCluer, J. W. (1989). Phenylthiocarbamide taste sensitivity revisited: Complete sorting test supports residual family resemblance. Genetic Epidemiology, 6(3), 413–421. https://doi.org/10.1002/gepi.1370060304
Page 25. This difference.
90. Kim, U., Jorgenson, E., Coon, H., Leppert, M., Risch, N., & Drayna, D. (2003). Positional Cloning of the Human Quantitative Trait Locus Underlying Taste Sensitivity to Phenylthiocarbamide. Science, 299(5610), 1221–1225. https://doi.org/10.1126/science.1080190
Page 25. The bones of seven Neanderthal.
91. Rosas Gonzalez, A., Estalrrich, A., García-Tabernero, A., Huguet, R., Lalueza-Fox, C., Ríos, L., Bastir, M., Fernández-Cascón, B., Perez-Criado, L., Rodriguez-Perez, F. J., Ferrando, A., Fernández-Cerezo, S., Sierra, E., & de la Rasilla, M. (2015). Paleoanthropological research of the neandertal fossils from 92. El Sidrón (Asturias, Spain). Cuaternario y Geomorfología, 29(3–4), 77–94. https://doi.org/10.17735/cyg.v29i3-4.40066
93. Rosas, A., Ríos, L., Estalrrich, A., Liversidge, H., García-Tabernero, A., Huguet, R., Cardoso, H., Bastir, M., Lalueza-Fox, C., de la Rasilla, M., & Dean, C. (2017). The growth pattern of Neandertals, reconstructed from a juvenile skeleton from El Sidrón (Spain). Science, 357(6357), 1282–1287. https://doi.org/10.1126/science.aan6463
Page 25. Scientists scraped the calcified tartar.
94. Hardy, K., Buckley, S., Collins, M. J., Estalrrich, A., Brothwell, D., Copeland, L., García-Tabernero, A., García-Vargas, S., Rasilla, M., Lalueza-Fox, C., Huguet, R., Bastir, M., Santamaría, D., Madella, M., Wilson, J., Cortés, Á. F., & Rosas, A. (2012). Neanderthal medics? Evidence for food, cooking, and medicinal plants entrapped in dental calculus. Naturwissenschaften, 99(8), 617–626. https://doi.org/10.1007/s00114-012-0942-0
95. Weyrich, L. S., Duchene, S., Soubrier, J., Arriola, L., Llamas, B., Breen, J., Morris, A. G., Alt, K. W., Caramelli, D., Dresely, V., Farrell, M., Farrer, A. G., Francken, M., Gully, N., Haak, W., Hardy, K., Harvati, K., Held, P., Holmes, E. C., … Cooper, A. (2017). Neanderthal behaviour, diet, and disease inferred from ancient DNA in dental calculus. Nature, 544(7650), 357–361. https://doi.org/10.1038/nature21674
Page 26. So perhaps Sid knew what he was doing.
96. Hardy, K. (2021). Paleomedicine and the Evolutionary Context of Medicinal Plant Use. Revista Brasileira de Farmacognosia, 31(1), 1–15. https://doi.org/10.1007/s43450-020-00107-4
Page 27. We diverged from a most.
97. Langergraber, K. E., Prüfer, K., Rowney, C., Boesch, C., Crockford, C., Fawcett, K., Inoue, E., Inoue-Muruyama, M., Mitani, J. C., Muller, M. N., Robbins, M. M., Schubert, G., Stoinski, T. S., Viola, B., Watts, D., Wittig, R. M., Wrangham, R. W., Zuberbühler, K., Pääbo, S., & Vigilant, L. (2012). Generation times in wild chimpanzees and gorillas suggest earlier divergence times in great ape and human evolution. Proceedings of the National Academy of Sciences, 109(39), 15716–15721. https://doi.org/10.1073/pnas.1211740109
Page 27. People use them to treat.
98. Burkill, H. M. (1985). The Useful Plants of West Tropical Africa, Vol. 1. 2nd ed. . Kew (UK): Royal Botanical Gardens.
99. Huffman, M. A. (2001). Self-Medicative Behavior in the African Great Apes: An Evolutionary Perspective into the Origins of Human Traditional Medicine: In addition to giving us a deeper understanding of our closest living relatives, the study of great ape self-medication provides a window into the origins of herbal medicine use by humans and promises to provide new insights into ways of treating parasite infections and other serious diseases. BioScience, 51(8), 651–661. https://doi.org/10.1641/0006-3568(2001)051[0651:SMBITA]2.0.CO;2
Page 27. In 1989.
100. Huffman, M. A., & Seifu, M. (1989). Observations on the illness and consumption of a possibly medicinal plant Vernonia amygdalina (Del.), by a wild chimpanzee in the Mahale Mountains National Park, Tanzania. Primates, 30(1), 51–63. https://doi.org/10.1007/BF02381210
Page 28. Over the next decade.
101. Huffman, M. A., Gotoh, S., Turner, L. A., Hamai, M., & Yoshida, K. (1997). Seasonal trends in intestinal nematode infection and medicinal plant use among chimpanzees in the Mahale Mountains, Tanzania. Primates, 38(2), 111–125. https://doi.org/10.1007/BF02382002
Page 28. Not only is food.
102. Rodriguez, E., & Wrangham, R. (1993). Zoopharmacognosy: The Use of Medicinal Plants by Animals. In Phytochemical Potential of Tropical Plants (pp. 89–105). Springer US. https://doi.org/10.1007/978-1-4899-1783-6_4
104. Morrogh-Bernard, H. C. (2008). Fur-Rubbing as a Form of Self-Medication in Pongo pygmaeus. International Journal of Primatology, 29(4), 1059–1064. https://doi.org/10.1007/s10764-008-9266-5
105. de la Fuente, M. F., Souto, A., Albuquerque, U. P., & Schiel, N. (2022). Self‐medication in nonhuman primates: A systematic evaluation of the possible function of the use of medicinal plants. American Journal of Primatology, 84(11). https://doi.org/10.1002/ajp.23438
Page 28. For example, in Borneo.
106. Morrogh-Bernard, H. C., Foitová, I., Yeen, Z., Wilkin, P., de Martin, R., Rárová, L., Doležal, K., Nurcahyo, W., & Olšanský, M. (2017). Self-medication by orangutans (Pongo pygmaeus) using bioactive properties of Dracaena cantleyi. Scientific Reports, 7(1), 16653. https://doi.org/10.1038/s41598-017-16621-w
Page 29. Indigenous people.
107. From abstract of below reference: “In Central Kalimantan, local indigenous people use the same species as an external medication to treat their arms after a stroke, for muscular pain, and for sore bones and swellings. Morrogh-Bernard, H. C. (2008). Fur-Rubbing as a Form of Self-Medication in Pongo pygmaeus. International Journal of Primatology, 29(4), 1059–1064. https://doi.org/10.1007/s10764-008-9266-5
Page 28. The main toxic constituent.
108. Gupta, D., Bleakley, B., & Gupta, R. K. (2008). Dragon’s blood: Botany, chemistry and therapeutic uses. Journal of Ethnopharmacology, 115(3), 361–380. https://doi.org/10.1016/j.jep.2007.10.018
109. Kougan, G. B., Miyamoto, T., Tanaka, C., Paululat, T., Mirjolet, J.-F., Duchamp, O., Sondengam, B. L., & Lacaille-Dubois, M.-A. (2010). Steroidal Saponins from Two Species of Dracaena. Journal of Natural Products, 73(7), 1266–1270. https://doi.org/10.1021/np100153m
110. Tapondjou, L. A., Ponou, K. B., Teponno, R. B., Mbiantcha, M., Djoukeng, J. D., Nguelefack, T. B., Watcho, P., Cadenas, A. G., & Park, H.-J. (2008). In vivo anti-inflammatory effect of a new steroidal saponin, mannioside A, and its derivatives isolated from Dracaena mannii. Archives of Pharmacal Research, 31(5), 653–658. https://doi.org/10.1007/s12272-001-1208-3
112. Martín, R. S., & Briones, R. (1999). Industrial uses and sustainable supply of Quillaja saponaria (Rosaceae) saponins. Economic Botany, 53(3), 302–311. https://doi.org/10.1007/BF02866642
Page 28. Remarkably, a saponin.
113. Pulendran, B., S. Arunachalam, P., & O’Hagan, D. T. (2021). Emerging concepts in the science of vaccine adjuvants. Nature Reviews Drug Discovery, 20(6), 454–475. https://doi.org/10.1038/s41573-021-00163-y
Page 30. The chemicals leaching. This refers to the tannins (tinting agents) and saponins (foaming agents) that many plants produce. “Root beer” from sarsaparilla root is one way this tonic was made by Indigenous and local people (from Smilax ornata, a plant native to Mexico and Central America) and it is possible that the saponins from this plant are responsible for the foaming effect, but see Ref. 109 below, which takes a more skeptical view given the concentrations involved. Another form of “root beer” was often made from sassafras root (Sassafras albidum), originally by Native Americans, until it was discovered that safrole was carcinogenic. Although some producers (e.g., Bundaberg) use sarsaparilla still, nowadays, some commercial beverage makers use saponins from other species like Quillaja saponaria to produce the foaming effect in some soft drinks. Sarsaparilla is both a drink and a reference to the plant, and root beer may or may not refer to sarsaparilla. For a light-hearted discussion of this issue see Ref. 111. Saponins are one, but not the only mechanism for the production of foam in blackwater rivers. Tannins in the strict sense, and phenolics in the broadest sense, contribute in a major way to the tinting of blackwater rivers.
116. Leung, A. Y. (1980). Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. John Wiley & Sons, New York.
117. Dietz, B., & Bolton, J. L. (2007). Botanical Dietary Supplements Gone Bad. Chemical Research in Toxicology, 20(4), 586–590. https://doi.org/10.1021/tx7000527
119. Janzen, D. H. (1974). Tropical Blackwater Rivers, Animals, and Mast Fruiting by the Dipterocarpaceae. Biotropica, 6(2), 69. https://doi.org/10.2307/2989823
Page 31. Nonetheless, some white wines.
120. “Total phenolic content (absorbance at 280 nm) was higher for white wines (Picapoll and Chardonnay) fermented in oak barrels than in stainless steel vats.” From: Ibern-Gómez, M., Andrés-Lacueva, C., Lamuela-Raventós, R. M., Lao-Luque, C., Buxaderas, S., & de la Torre-Boronat, M. C. (2001). Differences in Phenolic Profile between Oak Wood and Stainless Steel Fermentation in White Wines. American Journal of Enology and Viticulture, 52(2), 159–164. https://doi.org/10.5344/ajev.2001.52.2.159
Page 31. Although the structure is satisfying to the eye, it takes precious energy. The general idea is that constitutive (always present) and inducible (produced after attack) chemical defenses/deterrents, toxins sensu lato are costly to plant fitness (survival odds and reproductive output) in the absence of enemies. In the presence of enemies these chemical defenses/deterrents enhance fitness over what it would be if the plants didn’t make them or as much of them. The proximal cause of the enhanced fitness in the face of competition between plant genotypes (species) for resources (see August Pyramus de Candolle’s quote “All the plants of a given country, all those of a given place, are at war with one another.” in Chapter 3). Those plants able to survive and reproduce better than the others in this scenario are those that have enhanced defenses when in natural environments where attack by enemies like herbivores and microbial pathogens is de rigueur. The experimental, mechanistic evidence for this is strong and a few examples are given below, some of which take advantage of mutants wherein the principal chemical defense pathways are absent, or herbivores are excluded using pesticides, essentially lifting the governor on plant fitness as mediated by herbivory. The conclusion is that chemical defenses are costly to make in the absence of herbivores from a fitness perspective, and provide a benefit in the presence of herbivores generally that surmounts this cost and allows those endowed with the capacity to outcompete other plant genotypes. However, the chemical pathways to produce these chemicals and the chemicals themselves may also have other effects on the plant’s biology that are divorced from the defensive function per se. Put another way, pleiotropy–the effect of one gene on more than one trait in an organism-is pervasive.
122. Schultz, J. C., & Baldwin, I. T. (1982). Oak Leaf Quality Declines in Response to Defoliation by Gypsy Moth Larvae. Science, 217(4555), 149–151. https://doi.org/10.1126/science.217.4555.149
123. Coley, P. D., Bryant, J. P., & Chapin, F. S. (1985). Resource Availability and Plant Antiherbivore Defense. Science, 230(4728), 895–899. https://doi.org/10.1126/science.230.4728.895
124. Mauricio, R., & Rausher, M. D. (1997). Experimental manipulation of putative selective agents provides evidence for the role of natural enemies in the evolution of plant defense. Evolution, 51(5), 1435–1444. https://doi.org/10.1111/j.1558-5646.1997.tb01467.x
125. Baldwin, I. T. (1998). Jasmonate-induced responses are costly but benefit plants under attack in native populations. Proceedings of the National Academy of Sciences, 95(14), 8113–8118. https://doi.org/10.1073/pnas.95.14.8113
126. Kessler, A., Halitschke, R., & Baldwin, I. T. (2004). Silencing the Jasmonate Cascade: Induced Plant Defenses and Insect Populations. Science, 305(5684), 665–668. https://doi.org/10.1126/science.1096931
127. Zangerl, A. R., & Berenbaum, M. R. (2005). Increase in toxicity of an invasive weed after reassociation with its coevolved herbivore. Proceedings of the National Academy of Sciences, 102(43), 15529–15532. https://doi.org/10.1073/pnas.0507805102
128. Züst, T., Joseph, B., Shimizu, K. K., Kliebenstein, D. J., & Turnbull, L. A. (2011). Using knockout mutants to reveal the growth costs of defensive traits. Proceedings of the Royal Society B: Biological Sciences, 278(1718), 2598–2603. https://doi.org/10.1098/rspb.2010.2475
129. Agrawal, A. A., Hastings, A. P., Johnson, M. T. J., Maron, J. L., & Salminen, J.-P. (2012). Insect Herbivores Drive Real-Time Ecological and Evolutionary Change in Plant Populations. Science, 338(6103), 113–116. https://doi.org/10.1126/science.1225977
Page 32. Hydrolyzable tannins are derived from phenolic. This refers to the shikimate pathway.
130. Muir, R. M., Ibáñez, A. M., Uratsu, S. L., Ingham, E. S., Leslie, C. A., McGranahan, G. H., Batra, N., Goyal, S., Joseph, J., Jemmis, E. D., & Dandekar, A. M. (2011). Mechanism of gallic acid biosynthesis in bacteria (Escherichia coli) and walnut (Juglans regia). Plant Molecular Biology, 75(6), 555–565. https://doi.org/10.1007/s11103-011-9739-3
Page 32. Condensed tannins are flavonoids made by a more recently evolved. This refers to the phenylpropanoid pathway.
131. Chapple, C. C., Vogt, T., Ellis, B. E., & Somerville, C. R. (1992). An Arabidopsis mutant defective in the general phenylpropanoid pathway. The Plant Cell, 4(11), 1413–1424. https://doi.org/10.1105/tpc.4.11.1413
Page 32. Remarkably, gallotannins and other.
132. Aigner, S., Remias, D., Karsten, U., & Holzinger, A. (2013). Unusual phenolic compounds contribute to ecophysiological performance in the purple‐colored green alga Zygogonium ericetorum (Zygnematophyceae, Streptophyta) from a high‐alpine habitat. Journal of Phycology, 49(4), 648–660. https://doi.org/10.1111/jpy.12075
133. Newsome, A., & van Breemen, R. (2012). Characterization of the purple vacuolar pigment of Zygogonium ericatorum alga. Planta Medica, 78(11). https://doi.org/10.1055/s-0032-1321180
Page 32. Ultraviolet (UVB) light is highly damaging to DNA. UVB causes dimers to form between nucleotide sequences, often along the same DNA strand of the double-helix. Common dimers are cyclobutane pyrimidine dimers that then prevent the DNA from being transcribed into RNA or being replicated into DNA. An interesting example of the real-world effects of enhanced UVB radiation on terrestrial organisms (plants) is below, which was associated with “ozone hole” over Antarctica caused by anthropogenic chlorofluorocarbons that passed over southern Southern America in 1997.
134. Rousseaux, M. C., Ballaré, C. L., Giordano, C. v., Scopel, A. L., Zima, A. M., Szwarcberg-Bracchitta, M., Searles, P. S., Caldwell, M. M., & Díaz, S. B. (1999). Ozone depletion and UVB radiation: Impact on plant DNA damage in southern South America. Proceedings of the National Academy of Sciences, 96(26), 15310–15315. https://doi.org/10.1073/pnas.96.26.15310
Page 32. UVB light rapidly dissipates. (A) Suspended sediment (causing turbidity), pigmented phytoplankton that absorb some wavelengths of light (algae), and dissolved organic carbon (DOC) within water, absorb much of the UVB light in the water column. Yet, the variation in the degree of UVB attenuation is substantial across different bodies of both freshwater and saltwater. Moreover, there is non-trivial UVB penetration just below the surface that attenuates with depth, but the extent of this depends on many different factors. Algae growing underwater are more protected from the cumulative effects of UVB radiation on DNA damage compared to algae or plants growing on land. (B) Algae growing near the surface of the water certainly produce myriad chemicals to shield from UVB. For example, dinoflagellates that live as symbionts in corals, can be susceptible to UVB-driven DNA damage and indeed have evolved many different compounds that provide UVB protection. More generally, there is some controversy as to the importance of the higher UVB incidence on land in preventing its colonization by early life forms.
135. Dunne, R. P., & Brown, B. E. (1996). Penetration of solar UVB radiation in shallow tropical waters and its potential biological effects on coral reefs; results from the central Indian Ocean and Andaman Sea. Marine Ecology Progress Series, 144(1/3), 109–118. https://www.int-res.com/articles/meps/144/m144p109.pdf.
136. Tedetti, M., & Sempéré, R. (2006). Penetration of Ultraviolet Radiation in the Marine Environment. A Review. Photochemistry and Photobiology, 82(2), 389. https://doi.org/10.1562/2005-11-09-IR-733
137. V.-Balogh, K., Németh, B., & Vörös, L. (2009). Specific attenuation coefficients of optically active substances and their contribution to the underwater ultraviolet and visible light climate in shallow lakes and ponds. Hydrobiologia, 632(1), 91–105. https://doi.org/10.1007/s10750-009-9830-9
138. De Mora, S., Demers, S., & Vernet, M. (Eds.). (2000). The Effects of UV Radiation in the Marine Environment (Cambridge Environmental Chemistry Series). Cambridge: Cambridge University Press. https://doi.org/10.1017/CBO9780511535444
139. Wiencke, C., Gómez, I., Pakker, H., Flores-Moya, A., Altamirano, M., Hanelt, D., Bischof, K., & Figueroa, F. (2000). Impact of UV-radiation on viability, photosynthetic characteristics and DNA of brown algal zoospores:implications for depth zonation. Marine Ecology Progress Series, 197, 217–229. https://doi.org/10.3354/meps197217
140. Caldwell, M. M. (1971). Solar UV irradiation and the growth and development of higher plants. Photophysiology, 6, 131-177.
141. Karentz, D., McEuen, F. S., Land, M. C., & Dunlap, W. C. (1991). Survey of mycosporine-like amino acid compounds in Antarctic marine organisms: Potential protection from ultraviolet exposure. Marine Biology, 108(1), 157–166. https://doi.org/10.1007/BF01313484
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145. Cockell, C. S., & Raven, J. A. (2007). Ozone and life on the Archaean Earth. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences, 365(1856), 1889–1901. https://doi.org/10.1098/rsta.2007.2049
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146. Alston, R. E. (1958). An investigation of the purple vacuolar pigment of Zygogonium ericetorum and the status of “algal anthocyanins” and “phycoporphyrins.” American Journal of Botany, 45(9), 688–692. https://doi.org/10.1002/j.1537-2197.1958.tb12223.x
147. Newsome, A., & van Breemen, R. (2012). Characterization of the purple vacuolar pigment of Zygogonium ericatorum alga. Planta Medica, 78(11). https://doi.org/10.1055/s-0032-1321180
148. Aigner, S., Remias, D., Karsten, U., & Holzinger, A. (2013). Unusual phenolic compounds contribute to ecophysiological performance in the purple‐colored green alga Zygogonium ericetorum (Zygnematophyceae, Streptophyta) from a high‐alpine habitat. Journal of Phycology, 49(4), 648–660. https://doi.org/10.1111/jpy.12075
149. Herburger, K., Remias, D., & Holzinger, A. (2016). The green alga Zygogonium ericetorum (Zygnematophyceae, Charophyta) shows high iron and aluminium tolerance: protection mechanisms and photosynthetic performance. FEMS Microbiology Ecology, 92(8), fiw103. https://doi.org/10.1093/femsec/fiw103
Page 32. When these algae grow on ice.
150. Remias, D., Schwaiger, S., Aigner, S., Leya, T., Stuppner, H., & Lütz, C. (2012). Characterization of an UV- and VIS-absorbing, purpurogallin-derived secondary pigment new to algae and highly abundant in Mesotaenium berggrenii (Zygnematophyceae, Chlorophyta), an extremophyte living on glaciers. FEMS Microbiology Ecology, 79(3), 638–648. https://doi.org/10.1111/j.1574-6941.2011.01245.x
151. Yallop, M. L., Anesio, A. M., Perkins, R. G., Cook, J., Telling, J., Fagan, D., MacFarlane, J., Stibal, M., Barker, G., Bellas, C., Hodson, A., Tranter, M., Wadham, J., & Roberts, N. W. (2012). Photophysiology and albedo-changing potential of the ice algal community on the surface of the Greenland ice sheet. The ISME Journal, 6(12), 2302–2313. https://doi.org/10.1038/ismej.2012.107
Page 32. Once plants evolved on land.
152. “Of several people who tasted the aqueous extract, several reported a bitter or astringent taste.” From: Alston, R. E. (1958). An investigation of the purple vacuolar pigment of Zygogonium ericetorum and the status of “algal anthocyanins” and “phycoporphyrins.” American Journal of Botany, 45(9), 688–692. https://doi.org/10.1002/j.1537-2197.1958.tb12223.x
153. Yallop, M. L., Anesio, A. M., Perkins, R. G., Cook, J., Telling, J., Fagan, D., MacFarlane, J., Stibal, M., Barker, G., Bellas, C., Hodson, A., Tranter, M., Wadham, J., & Roberts, N. W. (2012). Photophysiology and albedo-changing potential of the ice algal community on the surface of the Greenland ice sheet. The ISME Journal, 6(12), 2302–2313. https://doi.org/10.1038/ismej.2012.107
154. Feeny, P. (1970). Seasonal Changes in Oak Leaf Tannins and Nutrients as a Cause of Spring Feeding by Winter Moth Caterpillars. Ecology, 51(4), 565–581. https://doi.org/10.2307/1934037
155. Feeny, P. (1976). Plant Apparency and Chemical Defense. In Biochemical Interaction Between Plants and Insects (pp. 1–40). Springer US. https://doi.org/10.1007/978-1-4684-2646-5_1
156. Hay, M. E., & Fenical, W. (1988). Marine Plant-Herbivore Interactions: The Ecology of Chemical Defense. Annual Review of Ecology and Systematics, 19(1), 111–145. https://doi.org/10.1146/annurev.es.19.110188.000551
158. Schultz, J. C., Hunter, M. D., & Appel, H. M. (1992). Antimicrobial Activity of Polyphenols Mediates Plant-Herbivore Interactions. In Plant Polyphenols (pp. 621–637). Springer US. https://doi.org/10.1007/978-1-4615-3476-1_35
159. Quideau, S., Feldman, K. S., & Appel, H. M. (1995). Chemistry of Gallotannin-Derived o-Quinones: Reactivity toward Nucleophiles. The Journal of Organic Chemistry, 60(16), 4982–4983. https://doi.org/10.1021/jo00121a012
160. Ossipov, V., Haukioja, E., Ossipova, S., Hanhimäki, S., & Pihlaja, K. (2001). Phenolic and phenolic-related factors as determinants of suitability of mountain birch leaves to an herbivorous insect. Biochemical Systematics and Ecology, 29(3), 223–240. https://doi.org/10.1016/S0305-1978(00)00069-7
Page 33. Condensed tannins evolved more recently. References below outline the origins of the phenylpropanoid pathway in plants and the potential antecedents of that pathway in some of their closest living algal relatives.
161. Delwiche, C. F., Graham, L. E., & Thomson, N. (1989). Lignin-Like Compounds and Sporopollen in Coleochaete , an Algal Model for Land Plant Ancestry. Science, 245(4916), 399–401. https://doi.org/10.1126/science.245.4916.399
162. Sørensen, I., Pettolino, F. A., Bacic, A., Ralph, J., Lu, F., O’Neill, M. A., Fei, Z., Rose, J. K. C., Domozych, D. S., & Willats, W. G. T. (2011). The charophycean green algae provide insights into the early origins of plant cell walls. The Plant Journal, 68(2), 201–211. https://doi.org/10.1111/j.1365-313X.2011.04686.x
163. Brillouet, J.-M., Romieu, C., Schoefs, B., Solymosi, K., Cheynier, V., Fulcrand, H., Verdeil, J.-L., & Conéjéro, G. (2013). The tannosome is an organelle forming condensed tannins in the chlorophyllous organs of Tracheophyta. Annals of Botany, 112(6), 1003–1014. https://doi.org/10.1093/aob/mct168
164. de Vries, S., Fürst‐Jansen, J. M. R., Irisarri, I., Dhabalia Ashok, A., Ischebeck, T., Feussner, K., Abreu, I. N., Petersen, M., Feussner, I., & de Vries, J. (2021). The evolution of the phenylpropanoid pathway entailed pronounced radiations and divergences of enzyme families. The Plant Journal, 107(4), 975–1002. https://doi.org/10.1111/tpj.15387
165. Rieseberg, T. P., Dadras, A., Fürst-Jansen, J. M. R., Dhabalia Ashok, A., Darienko, T., de Vries, S., Irisarri, I., & de Vries, J. (2023). Crossroads in the evolution of plant specialized metabolism. Seminars in Cell & Developmental Biology, 134, 37–58. https://doi.org/10.1016/j.semcdb.2022.03.004
Page 33. Made of two or more catechin.
166. Mole, S. (1993). The systematic distribution of tannins in the leaves of angiosperms: A tool for ecological studies. Biochemical Systematics and Ecology, 21(8), 833–846. https://doi.org/10.1016/0305-1978(93)90096-A
167. Puupponen-Pimia, R., Nohynek, L., Meier, C., Kahkonen, M., Heinonen, M., Hopia, A., & Oksman-Caldentey, K.-M. (2001). Antimicrobial properties of phenolic compounds from berries. Journal of Applied Microbiology, 90(4), 494–507. https://doi.org/10.1046/j.1365-2672.2001.01271.x
Page 33. In moderate amounts.
168. Chung, K.-T., Wei, C.-I., & Johnson, M. G. (1998). Are tannins a double-edged sword in biology and health? Trends in Food Science & Technology, 9(4), 168–175. https://doi.org/10.1016/S0924-2244(98)00028-4
169. Maugeri, A., Lombardo, G. E., Cirmi, S., Süntar, I., Barreca, D., Laganà, G., & Navarra, M. (2022). Pharmacology and toxicology of tannins. Archives of Toxicology, 96(5), 1257–1277. https://doi.org/10.1007/s00204-022-03250-0
171. Bieschke, J., Russ, J., Friedrich, R. P., Ehrnhoefer, D. E., Wobst, H., Neugebauer, K., & Wanker, E. E. (2010). EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity. Proceedings of the National Academy of Sciences, 107(17), 7710–7715. https://doi.org/10.1073/pnas.0910723107
172. Borges, C. M., Papadimitriou, A., Duarte, D. A., Lopes de Faria, J. M., & Lopes de Faria, J. B. (2016). The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial. Scientific Reports, 6(1), 28282. https://doi.org/10.1038/srep28282
Page 33. However, EGCG pills.
173. Younes, M., Aggett, P., Aguilar, F., Crebelli, R., Dusemund, B., Filipič, M., Frutos, M. J., Galtier, P., Gott, D., Gundert‐Remy, U., Lambré, C., Leblanc, J., Lillegaard, I. T., Moldeus, P., Mortensen, A., Oskarsson, A., Stankovic, I., Waalkens‐Berendsen, I., Woutersen, R. A., … Wright, M. (2018). Scientific opinion on the safety of green tea catechins. EFSA Journal, 16(4). https://doi.org/10.2903/j.efsa.2018.5239
Page 33. I became aware of the dangers.
174. Patel, S. S. (2013). Green tea extract: A potential cause of acute liver failure. World Journal of Gastroenterology, 19(31), 5174. https://doi.org/10.3748/wjg.v19.i31.5174
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175. Hoofnagle, J. H. (2013). Chapter 40 - LiverTox: A website on drug-induced liver Injury. Editor(s): N. Kaplowitz, and L. D. DeLeve. Drug-Induced Liver Disease (3rd Edition), Academic Press, Pp. 725–732. Accessed July 3, 2023: https://doi.org/10.1016/B978-0-12-387817-5.00040-6.
Page 33. LiverTox focuses on toxins.
176. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; (2012-). Available from: https://www.ncbi.nlm.nih.gov/books/NBK547852/
Page 34. Stilbenoids are one of these. References below relate to to what extent the stilbenoid resveratrol may or may not have as an anti-aging “drug” or to treat disease. Resveratrol’s role in anti-aging via activation of sirtuins (proteins involved in metabolic activation) remains a highly contested topic in the scientific literature.
177. Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., Lavu, S., Wood, J. G., Zipkin, R. E., Chung, P., Kisielewski, A., Zhang, L.-L., Scherer, B., & Sinclair, D. A. (2003). Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature, 425(6954), 191–196. https://doi.org/10.1038/nature01960
178. Wood, J. G., Rogina, B., Lavu, S., Howitz, K., Helfand, S. L., Tatar, M., & Sinclair, D. (2004). Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature, 430(7000), 686–689. https://doi.org/10.1038/nature02789
179. Burnett, C., Valentini, S., Cabreiro, F., Goss, M., Somogyvári, M., Piper, M. D., Hoddinott, M., Sutphin, G. L., Leko, V., McElwee, J. J., Vazquez-Manrique, R. P., Orfila, A.-M., Ackerman, D., Au, C., Vinti, G., Riesen, M., Howard, K., Neri, C., Bedalov, A., … Gems, D. (2011). Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature, 477(7365), 482–485. https://doi.org/10.1038/nature10296
180. Related to a trial of a proprietary formulation of resveratrol as a multiple myeloma treatment: “a mid-stage Phase II study of SRT501 in patients with multiple myeloma was suspended last May after some patients with the disease, which is a type of blood cancer, developed kidney problems.” From Glaxo drops version of resveratrol “red wine” drug. Reuters (Reporting by Ben Hirschler; Editing by Will Waterman): Accessed July, 3, 2023: https://www.reuters.com/article/glaxo-resveratrol/glaxo-drops-version-of-resveratrol-red-wine-drug-idUSLDE6B025W20101201.
181. Kaeberlein, M., McDonagh, T., Heltweg, B., Hixon, J., Westman, E. A., Caldwell, S. D., Napper, A., Curtis, R., DiStefano, P. S., Fields, S., Bedalov, A., & Kennedy, B. K. (2005). Substrate-specific Activation of Sirtuins by Resveratrol. Journal of Biological Chemistry, 280(17), 17038–17045. https://doi.org/10.1074/jbc.M500655200
182. Schmidt, C. (2010). GSK/Sirtris compounds dogged by assay artifacts. Nature Biotechnology, 28(3), 185–186. https://doi.org/10.1038/nbt0310-185
183. Hubbard, B. P., Gomes, A. P., Dai, H., Li, J., Case, A. W., Considine, T., Riera, T. v., Lee, J. E., E, S. Y., Lamming, D. W., Pentelute, B. L., Schuman, E. R., Stevens, L. A., Ling, A. J. Y., Armour, S. M., Michan, S., Zhao, H., Jiang, Y., Sweitzer, S. M., … Sinclair, D. A. (2013). Evidence for a Common Mechanism of SIRT1 Regulation by Allosteric Activators. Science, 339(6124), 1216–1219. https://doi.org/10.1126/science.1231097
185. Huynh, A. T., Nguyen, T.-T. N., Villegas, C. A., Montemorso, S., Strauss, B., Pearson, R. A., Graham, J. G., Oribello, J., Suresh, R., Lustig, B., & Wang, N. (2022). Prediction and confirmation of a switch-like region within the N-terminal domain of hSIRT1. Biochemistry and Biophysics Reports, 30, 101275. https://doi.org/10.1016/j.bbrep.2022.101275
186. The 60 minutes story about the “French Paradox” and potential of resveratrol as or certain formulations of it as a drug. From the CBS website: “This story was first published on Jan. 25, 2009. It was updated on May 21, 2009.” Accessed July 3, 2023: https://www.cbsnews.com/news/fountain-of-youth-in-a-wine-rx/.
Page 34. Coumarin, which underlies. The reference below cites the salient literature and provides a good primer on the origins of warfarin and connection to moldy clover and to dicoumarol
Page 34. Warfarin is also effective as a rodenticide.
188. Herring, G., Eagles-Smith, C. A., & Buck, J. (2017). Characterizing Golden Eagle Risk to Lead and Anticoagulant Rodenticide Exposure: A Review. Journal of Raptor Research, 51(3), 273–292. https://doi.org/10.3356/JRR-16-19.1
189. Hofstadter, D. F., Kryshak, N. F., Gabriel, M. W., Wood, C. M., Wengert, G. M., Dotters, B. P., Roberts, K. N., Fountain, E. D., Kelly, K. G., Keane, J. J., Whitmore, S. A., Berigan, W. J., & Peery, M. Z. (2021). High rates of anticoagulant rodenticide exposure in California Barred Owls are associated with the wildland–urban interface. Ornithological Applications, 123(4). https://doi.org/10.1093/ornithapp/duab036
Page 35. As a junior in college. The study abroad program in fall semester 1996 was run through St. John’s University and the College of St. Benedict in Stearns County, Minnesota and was based at the Collège International de Cannes, in Canne, France. 192. Accessed July 3, 2023: https://www.french-in-cannes.fr/.
194. Soares, S., Ferrer-Galego, R., Brandão, E., Silva, M., Mateus, N., & Freitas, V. de. (2016). Contribution of Human Oral Cells to Astringency by Binding Salivary Protein/Tannin Complexes. Journal of Agricultural and Food Chemistry, 64(41), 7823–7828. https://doi.org/10.1021/acs.jafc.6b02659
Page 35. In our mouths.
195. McArthur, C., Sanson, G. D., & Beal, A. M. (1995). Salivary proline-rich proteins in mammals: Roles in oral homeostasis and counteracting dietary tannin. Journal of Chemical Ecology, 21(6), 663–691. https://doi.org/10.1007/BF02033455
Page 35. When tannins bind.
196. Torregrossa, A.-M., Nikonova, L., Bales, M. B., Villalobos Leal, M., Smith, J. C., Contreras, R. J., & Eckel, L. A. (2014). Induction of Salivary Proteins Modifies Measures of Both Orosensory and Postingestive Feedback during Exposure to a Tannic Acid Diet. PLoS ONE, 9(8), e105232. https://doi.org/10.1371/journal.pone.0105232
Page 35. Tannins can benefit the plants. For the relationship between tannins and plant fitness see references above. Note that in large animals like us, tannins bind to proteins and may prevent absorption of nutrients but the mechanism driving toxicity in herbivorous insects is likely to be driven by tannin oxidation and other effects not directly driving malabsorption via protein-binding, although this may vary depending on the pH level found in the gut.
197. Appel, H. M. (1993). Phenolics in ecological interactions: The importance of oxidation. Journal of Chemical Ecology, 19(7), 1521–1552. https://doi.org/10.1007/BF00984895
198. Felton, G. W., Donato, K. K., Broadway, R. M., & Duffey, S. S. (1992). Impact of oxidized plant phenolics on the nutritional quality of dietary protein to a noctuid herbivore, Spodoptera exigua. Journal of Insect Physiology, 38(4), 277–285. https://doi.org/10.1016/0022-1910(92)90128-Z
199. Salminen, J., & Karonen, M. (2011). Chemical ecology of tannins and other phenolics: we need a change in approach. Functional Ecology, 25(2), 325–338. https://doi.org/10.1111/j.1365-2435.2010.01826.x
200. Robbins, C. T., Hanley, T. A., Hagerman, A. E., Hjeljord, O., Baker, D. L., Schwartz, C. C., & Mautz, W. W. (1987). Role of Tannins in Defending Plants Against Ruminants: Reduction in Protein Availability. Ecology, 68(1), 98–107. https://doi.org/10.2307/1938809
201. DeGabriel, J. L., Moore, B. D., Foley, W. J., & Johnson, C. N. (2009). The effects of plant defensive chemistry on nutrient availability predict reproductive success in a mammal. Ecology, 90(3), 711–719. https://doi.org/10.1890/08-0940.1
Page 36. Tannic and gallic acids were.
202. Zboralske, F. F., Harris, P. a., Riegelman, S., Rambo, O. N., & Margulis, A. R. (1966). Toxicity Studies on Tannic acid Administered by Enema. American Journal of Roentgenology, 96(2), 505–509. https://doi.org/10.2214/ajr.96.2.505
203. McAlister, W. H., Anderson, M. S., Bloomberg, G. R., & Margulis, A. R. (1963). Lethal Effects of Tannic Acid in the Barium Enema. Radiology, 80(5), 765–773. https://doi.org/10.1148/80.5.765
205. Stone, G. N., & Cook, J. M. (1998). The structure of cynipid oak galls: patterns in the evolution of an extended phenotype. Proceedings of the Royal Society of London. Series B: Biological Sciences, 265(1400), 979–988. https://doi.org/10.1098/rspb.1998.0387
206. Redfern, M. (2011). Plant galls. London, UK: HarperCollins Publishers.
Page 36. These are oak galls, or oak apples.
207. Bronner, N. (1992). The role of nutritive cells in the nutrition of cynipids and cecidomyiids. Biology of insect-induced galls. Oxford University Press, Oxford, pp 118–140.
Page 36. The galls are neoplasms.
208. White, P. R. (1951). Neoplastic Growth in Plants. The Quarterly Review of Biology, 26(1), 1–16. https://doi.org/10.1086/397879
Page 36. Like some cervical cancers.
209. zur Hausen, H., de Villiers, E.-M., & Gissmann, L. (1981). Papillomavirus infections and human genital cancer. Gynecologic Oncology, 12(2), S124–S128. https://doi.org/10.1016/0090-8258(81)90067-6
210. Boshart, M., Gissmann, L., Ikenberg, H., Kleinheinz, A., Scheurlen, W., & zur Hausen, H. (1984). A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. The EMBO Journal, 3(5), 1151–1157. https://doi.org/10.1002/j.1460-2075.1984.tb01944.x
Page 36. In oaks, the galls are induced.
211. Stone, G. N., & Schönrogge, K. (2003). The adaptive significance of insect gall morphology. Trends in Ecology & Evolution, 18(10), 512–522. https://doi.org/10.1016/S0169-5347(03)00247-7
212. Egan, S. P., Hood, G. R., Martinson, E. O., & Ott, J. R. (2018). Cynipid gall wasps. Current Biology, 28(24), R1370–R1374. https://doi.org/10.1016/j.cub.2018.10.028
Page 36. Through largely unknown mechanisms.
213. Hearn, J., Blaxter, M., Schönrogge, K., Nieves-Aldrey, J.-L., Pujade-Villar, J., Huguet, E., Drezen, J.-M., Shorthouse, J. D., & Stone, G. N. (2019). Genomic dissection of an extended phenotype: Oak galling by a cynipid gall wasp. PLOS Genetics, 15(11), e1008398. https://doi.org/10.1371/journal.pgen.1008398
Page 36. As the oak gall grows.
214. Cornell, H. V. (1983). The Secondary Chemistry and Complex Morphology of Galls Formed by the Cynipinae (Hymenoptera): Why and How? The American Midland Naturalist, 110(2), 225–234. https://doi.org/10.2307/2425263
Page 36. The oak tree produces.
215. Feeny, P. (1970). Seasonal Changes in Oak Leaf Tannins and Nutrients as a Cause of Spring Feeding by Winter Moth Caterpillars. Ecology, 51(4), 565–581. https://doi.org/10.2307/1934037
Page 37. We tried to reconcile.
216. The Declaration of Independence. “He has excited domestic insurrections amongst us, and has endeavoured to bring on the inhabitants of our frontiers, the merciless Indian Savages, whose known rule of warfare, is an undistinguished destruction of all ages, sexes and conditions.” Accessed July 4, 2023: https://www.archives.gov/founding-docs/declaration-transcript.
Page 37. What I didn’t know then.
217. Mitchell, C. A.; Hepworth, T. C. (1904). Inks: Their Composition and Manufacture; Charles Griffin & Company, Ltd.: London, UK.
218. Kolar, J., Štolfa, A., Strlič, M., Pompe, M., Pihlar, B., Budnar, M., Simčič, J., & Reissland, B. (2006). Historical iron gall ink containing documents — Properties affecting their condition. Analytica Chimica Acta, 555(1), 167–174. https://doi.org/10.1016/j.aca.2005.08.073
Page 38. Roughly between 400 and 1800 CE.
219. Stijnman, A. 2006. Iron-gall inks in history: ingredients and production. In: Kolar J, Strlič M, editors. Iron–gall Inks: on manufacture, characterization, degradation and stabilization. Ljubljana: National and University Library, p. 25–167 (and Appendix 4).
220. Díaz Hidalgo, R. J., Córdoba, R., Nabais, P., Silva, V., Melo, M. J., Pina, F., Teixeira, N., & Freitas, V. (2018). New insights into iron-gall inks through the use of historically accurate reconstructions. Heritage Science, 6(1), 63. https://doi.org/10.1186/s40494-018-0228-8
Page 37. Even more remarkable. It is important to note that iron gall ink itself wasn’t found in the Thanksgiving Scroll of the Dead Sea Scrolls. However, a study by Hahn et al. below showed that the ink from some scrolls does contain chemicals with spectra that are consistent with hydrolyzable tannins and that this was consistent with use of oak galls or other galls (e.g., from sumac) to make the ink. Moreover, Hahn et al. hypothesize that the protein (collagen) binding properties of tannins suggests that the tannins may indeed allow the inks to persist for such a long time. This would likely not have been the case if iron was included in the ink owing to the acidity. So, the black ink of the Dead Sea Scrolls indeed, in some cases, seems to contain hydrolyzable tannins. This is an active area of research. The relevant passages from pages 101 and 102 of that reference are as follows:
“The solid line in fig. 3 is the first Fourier Transform Infra-Red (FTIR) spectrum of Dead Sea Scroll ink ever reported. Its shape is similar to that of natural gum. However its many peaks are sharper, suggesting the presence of tannins and aromatic compounds. Two types of vegetable tannins can be distinguished based on their infrared spectra: condensed and hydrolysable tannins. The former are of phenolic nature and do not have carboxylic groups whereas the latter (e.g.: gallic acid) do possess such groups [17,18].”
“To our astonishment the best correspondence was found when comparing the spectra of the ink from the scroll with a sample of ours prepared according to Maimonides recipe, dating from the 12th century (grey curve) [21]. Curiously enough, Maimonides recommends adding gall nuts extract to the common ingredients of the carbon black ink, without mentioning any reason. For the preparation of our sample we used commercial Gum Arabic and oak galls. The infrared spectra obtained combining tannins with natural resin seems to fit much better the experimental results from the original ink than the spectra obtained using single type of binders. Thus, the direct addition of a tannic agent to the inks cannot be excluded: Maimonides’ prescription could indicate the survival of an ancient use, whose actual reason had been forgotten. In this case the tannins would chemically bind the ink to the parchment collagen [22], explaining the surprising durability of the scroll inks as compared to the usual, physisorbed, carbon-based ink.”
221. Hahn, O., Weinberg, G., Rabin, I., Wolff, T., & Masic, A. (2009). On the Origin of the Ink of the Thanksgiving Scroll (1QHodayota). Dead Sea Discoveries, 16(1), 97–106. https://doi.org/10.1163/156851709X395722
Page 37. When hydrolyzable tannins.
222. Espina, A., Cañamares, M. V., Jurašeková, Z., & Sanchez-Cortes, S. (2022). Analysis of Iron Complexes of Tannic Acid and Other Related Polyphenols as Revealed by Spectroscopic Techniques: Implications in the Identification and Characterization of Iron Gall Inks in Historical Manuscripts. ACS Omega, 7(32), 27937–27949. https://doi.org/10.1021/acsomega.2c01679
Page 38. Iron gall ink and quill pens.
223. Carvalho, D. N. 2007. Forty Centuries of Ink. Echo Library.
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Page 38. Leonardo da Vinci.
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Page 39. For hundreds of years.
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228. Redwood, M. (2016). Gloves and Glove-making. Oxford, Shire Publications Ltd.
Page 40. Each year we collectively swallow120 billion bitter doses.
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Page 40. In 1763, when.
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Page 41. Proof that these chemicals.
232. Green, P. W. C., Simmonds, M. S. J., & Blaney, W. M. (2002). Toxicity and behavioural effects of diet-borne alkaloids on larvae of the black blowfly, Phormia regina. Medical and Veterinary Entomology, 16(2), 157–160. https://doi.org/10.1046/j.1365-2915.2002.00358.x
Page 41. Even more remarkably.
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Page 41. Of course, quinine. Although quinine was the first line of defense against malaria, notably, many populations of Plasmodium have evolved resistance to quinine and its derivative molecules, like chloroquine and mefloquine.
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Page 43. The high concentrations of salicylates in willows.
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Page 43. The most ancient role of salicylates in plants.
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Page 43. I was completely shocked to learnthat.
244. Paterson, J. R., Baxter, G., Dreyer, J. S., Halket, J. M., Flynn, R., & Lawrence, J. R. (2008). Salicylic Acid sans Aspirin in Animals and Man: Persistence in Fasting and Biosynthesis from Benzoic Acid. Journal of Agricultural and Food Chemistry, 56(24), 11648–11652. https://doi.org/10.1021/jf800974z
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Page 43. Plants also make prostaglandin-like. Oxylipins include both prostaglandins produced by animals and jasmonates produced by plants.
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Page 46. So, you may have experienced the.
254. Blacklock, C. J. (2001). Salicylic acid in the serum of subjects not taking aspirin. Comparison of salicylic acid concentrations in the serum of vegetarians, non-vegetarians, and patients taking low dose aspirin. Journal of Clinical Pathology, 54(7), 553–555. https://doi.org/10.1136/jcp.54.7.553
Page 46. For example, the incidence of colon cancer.
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Page 46. Much of the salicylic acid in the diet.
256. Paterson, J. R., Srivastava, R., Baxter, G. J., Graham, A. B., & Lawrence, J. R. (2006). Salicylic Acid Content of Spices and Its Implications. Journal of Agricultural and Food Chemistry, 54(8), 2891–2896. https://doi.org/10.1021/jf058158w
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Page 46. Ironically, some people take.
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Page 46. This practice is no longer recommended.
259. Davidson, K. W., Barry, M. J., Mangione, C. M., Cabana, M., Chelmow, D., Coker, T. R., Davis, E. M., Donahue, K. E., Jaén, C. R., Krist, A. H., Kubik, M., Li, L., Ogedegbe, G., Pbert, L., Ruiz, J. M., Stevermer, J., Tseng, C.-W., & Wong, J. B. (2022). Aspirin use to prevent cardiovascular disease. JAMA, 327(16), 1577. https://doi.org/10.1001/jama.2022.4983
Page 46. The same now goes.
260. Cao, Y., Nishihara, R., Wu, K., Wang, M., Ogino, S., Willett, W. C., Spiegelman, D., Fuchs, C. S., Giovannucci, E. L., & Chan, A. T. (2016). Population-wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncology, 2(6), 762. https://doi.org/10.1001/jamaoncol.2015.6396
261. Guo, C.-G., Ma, W., Drew, D. A., Cao, Y., Nguyen, L. H., Joshi, A. D., Ng, K., Ogino, S., Meyerhardt, J. A., Song, M., Leung, W. K., Giovannucci, E. L., & Chan, A. T. (2021). Aspirin use and risk of colorectal cancer among older adults. JAMA Oncology, 7(3), 428. https://doi.org/10.1001/jamaoncol.2020.7338
263. Li, L., Geraghty, O. C., Mehta, Z., & Rothwell, P. M. (2017). Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study. The Lancet, 390(10093), 490–499. https://doi.org/10.1016/S0140-6736(17)30770-5
Page 47. Across the Northern Hemisphere.
264. Smiley, J. T., Horn, J. M., & Rank, N. E. (1985). Ecological Effects of Salicin at Three Trophic Levels: New Problems from Old Adaptations. Science, 229(4714), 649–651. https://doi.org/10.1126/science.229.4714.649
Page 47. Many species in this plant.
265. Kirsch, R., Vogel, H., Muck, A., Vilcinskas, A., Pasteels, J. M., & Boland, W. (2011). To be or not to be convergent in salicin-based defence in chrysomeline leaf beetle larvae: evidence from Phratora vitellinae salicyl alcohol oxidase. Proceedings. Biological Sciences, 278(1722), 3225–3232. https://doi.org/10.1098/rspb.2011.0175
Page 47. This chemical, released from a beetle gland.
266. Smiley, J. T., Horn, J. M., & Rank, N. E. (1985). Ecological Effects of Salicin at Three Trophic Levels: New Problems from Old Adaptations. Science, 229(4714), 649–651. https://doi.org/10.1126/science.229.4714.649
Page 48. Schoolchildren in the San Francisco Bay Area.
268. Kästner, J., von Knorre, D., Himanshu, H., Erb, M., Baldwin, I. T., & Meldau, S. (2014). Salicylic Acid, a Plant Defense Hormone, Is Specifically Secreted by a Molluscan Herbivore. PLoS ONE, 9(1), e86500. https://doi.org/10.1371/journal.pone.0086500
Page 48. In addition to providing. See preceding reference and another that shows the suppression of jasmonate-dependent defense signaling via salicylates in slug slime is still unclear:
269. Meldau, S., Kästner, J., von Knorre, D., & Baldwin, I. T. (2014). Salicylic acid-dependent gene expression is activated by locomotion mucus of different molluscan herbivores. Communicative & Integrative Biology, 7(3), e28728. https://doi.org/10.4161/cib.28728
274. Pathak, M. A., Daniels, F., & Fitzpatrick, T. B. (1962). The Presently Known Distribution of Furocoumarins (Psoralens) in Plants. Journal of Investigative Dermatology, 39(3), 225–239. https://doi.org/10.1038/jid.1962.106
275. Berenbaum, M. (1983). Coumarins and Caterpillars: A Case for Coevolution. Evolution, 37(1), 163. https://doi.org/10.2307/2408184
Page 48. Because furanocourmarins are contained in.
276. U.S. Food and Drug Administration. (2021, July 1). Grapefruit Juice and Some Drugs Don’t Mix.
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278. Bailey, D. G., Dresser, G., & Arnold, J. M. O. (2013). Grapefruit–medication interactions: Forbidden fruit or avoidable consequences? Canadian Medical Association Journal, 185(4), 309–316. https://doi.org/10.1503/cmaj.120951
Page 49. The activity of an important drug metabolism enzyme.
279. Guo, L. Q., Fukuda, K., Ohta, T., & Yamazoe, Y. (2000). Role of furanocoumarin derivatives on grapefruit juice-mediated inhibition of human CYP3A activity. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 28(7), 766–771.
280. Bailey, D., Spence, J., Munoz, C., & Arnold, J. M. O. (1991). Interaction of citrus juices with felodipine and nifedipine. The Lancet, 337(8736), 268–269. https://doi.org/10.1016/0140-6736(91)90872-M
281. Wangensteen, H., Molden, E., Christensen, H., & Malterud, K. E. (2003). Identification of epoxybergamottin as a CYP3A4 inhibitor in grapefruit peel. European Journal of Clinical Pharmacology, 58(10), 663–668. https://doi.org/10.1007/s00228-002-0537-3
Page 49. A twenty-nine-year-old man.
282. Spence, J. D. (1997). Drug interactions with grapefruit: Whose responsibility is it to warn the public? Clinical Pharmacology & Therapeutics, 61(4), 395–400. https://doi.org/10.1016/S0009-9236(97)90189-2
Page 49. In all, there are eight-five.
283. Bailey, D., Spence, J., Munoz, C., & Arnold, J. M. O. (1991). Interaction of citrus juices with felodipine and nifedipine. The Lancet, 337(8736), 268–269. https://doi.org/10.1016/0140-6736(91)90872-M
Page 49. Furanocoumarins can also cause third-degree.
285. Melough, M. M., & Chun, O. K. (2018). Dietary furocoumarins and skin cancer: A review of current biological evidence. Food and Chemical Toxicology, 122, 163–171. https://doi.org/10.1016/j.fct.2018.10.027
Page 50. Although I don’t want to scare you.
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Page 50. Burns have even led.
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Page 59. Psoralen, the principal.
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Page 50. In fact, furanocoumarins.
291. Hönigsmann, H. (2012). History of phototherapy in dermatology. Photochemical & Photobiological Sciences, 12(1), 16–21. https://doi.org/10.1039/c2pp25120e
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Page 50. Building on knowledge.
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Page 51. It is also used against.
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Page 51. A clinical trial is.
296. Oldham, M., Yoon, P., Fathi, Z., Beyer, W. F., Adamson, J., Liu, L., Alcorta, D., Xia, W., Osada, T., Liu, C., Yang, X. Y., Dodd, R. D., Herndon, J. E., Meng, B., Kirsch, D. G., Lyerly, H. K., Dewhirst, M. W., Fecci, P., Walder, H., & Spector, N. L. (2016). X-Ray Psoralen Activated Cancer Therapy (X-PACT). PLOS ONE, 11(9), e0162078. https://doi.org/10.1371/journal.pone.0162078
Page 51. Psoralen was used sometimes.
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Page 51. The dried fruits of.
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299. Hönigsmann, H. (2012). History of phototherapy in dermatology. Photochemical & Photobiological Sciences, 12(1), 16–21. https://doi.org/10.1039/c2pp25120e
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Page 51. For example, entomologist May Berenbaum.
302. Berenbaum, M. (1978). Toxicity of a Furanocoumarin to Armyworms: A Case of Biosynthetic Escape from Insect Herbivores. Science, 201(4355), 532–534. https://doi.org/10.1126/science.201.4355.532
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Page 52. Berenbaum has used this.
304. Berenbaum, M. (1983). Coumarins and Caterpillars: A Case for Coevolution. Evolution, 37(1), 163. https://doi.org/10.2307/2408184
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Page 53. In the days after his death. For an introduction on shirin-yoku or forest bathing see:
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Page 53 and 54. I got what I had come for. The quote “frosty pepper up my nose” is from Robert Louis Stevenson’s poem Winter-Time:
309. Stevenson, R. L. (1885). XXXVIII. Winter-Time. In: A Child’s Garden of Verses. Longmans, Green, and Company, London. See: https://en.wikisource.org/wiki/A_Child%27s_Garden_of_Verses Late lies the wintry sun a-bed, A frosty, fiery sleepy-head; Blinks but an hour or two; and then, A blood-red orange, sets again.
Before the stars have left the skies, At morning in the dark I rise; And shivering in my nakedness, By the cold candle, bathe and dress.
Close by the jolly fire I sit To warm my frozen bones a bit; Or with a reindeer-sled, explore The colder countries round the door.
When to go out, my nurse doth wrap Me in my comforter and cap; The cold wind burns my face, and blows Its frosty pepper up my nose.
Black are my steps on silver sod; Thick blows my frosty breath abroad; And tree and house, and hill and lake, Are frosted like a wedding-cake.
Page 54. Terpenoids are the largest.
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Page 54. So important areterpenoids.
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Page 54. Our bodies make isoprene.
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Page 54. We emit so much isoprene.
320. Veres, P. R., Faber, P., Drewnick, F., Lelieveld, J., & Williams, J. (2013). Anthropogenic sources of VOC in a football stadium: Assessing human emissions in the atmosphere. Atmospheric Environment, 77, 1052–1059. https://doi.org/10.1016/j.atmosenv.2013.05.076
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Page 54. Isoprene can protect.
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Page 55. The amount of isoprene.
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Page 55. It was through.
330. Whaley, W. G. (1948). Rubber-The Primary Sources For American Production. Economic Botany, 2(2), 198–216. https://doi.org/10.1007/BF02859004
Page 56. More than twenty thousand. This reference also supports the rest of this paragraph.
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Page 56. The Congo rubber vine. This reference also supports the rest of this paragraph.
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334. Hochschild, A. (1998). King Leopold’s Ghost: A Story of Greed, Terror, and Heroism in Colonial Africa. Mariner Books.
Page 56. An early act of biopiracy.
335. Page Jackson, J. (2008). The Thief at the End of the World: Rubber, Power, and the Seeds of Empire. Penguin
Page 56. Some of the rubber tree.
336. Loadman, J. (2005). Tears of the Tree: The Story of Rubber - A Modern Marvel. OUP Oxford.
Page 56 and 57. The juggernaut and the blight.
337. Davis, W. (1997). One river: Science, adventure and hallucinogenics in the Amazon Basin. Simon & Schuster Londres.
Page 57. The United States could not have.
338. Neeleman, G. & Neeleman, R. (2017). Rubber Soldiers: The Forgotten Army that Saved the Allies in WWII. Schiffer Publishing, Limited.
Page 57. My only memory.
339. Florida. - Division of Tourism. Banyan tree by Thomas Edison's house in Fort Myers, Florida. 20th century. State Archives of Florida, Florida Memory. https://www.floridamemory.com/items/show/92761, accessed 5 October 2023.
Page 57. I later learned. These references apply to the three paragraphs that follow.
340. Finlay, M. R. (2009). Growing American Rubber: Strategic Plants and the Politics of National Security. Rutgers University Press. http://www.jstor.org/stable/j.ctt5hhx8h
344. Agrawal, A. A., & Konno, K. (2009). Latex: A Model for Understanding Mechanisms, Ecology, and Evolution of Plant Defense Against Herbivory. Annual Review of Ecology, Evolution, and Systematics, 40(1), 311–331. https://doi.org/10.1146/annurev.ecolsys.110308.120307
Page 58. Early last year.
345. Text message to Noah Whiteman from Karin Fyhrie on January 20, 2021
Page 58. We had been fooled.
346. Losos, J. (2017). Improbable destinies: how predictable is evolution? Penguin UK.
Page 58. The terpenoidsin the latex.
347. Sofat, B. K., Sood, G. C., Chandel, R. D., & Mehrotra, S. K. (1972). Euphorbia royleana latex keratitis. Am. J. Ophthalmol., 74(4), 634–637. https://doi.org/10.1016/0002-9394(72)90825-2
348. Scott, I. U., & Karp, C. L. (1996). Euphorbia sap keratopathy: four cases and a possible pathogenic mechanism. British Journal of Ophthalmology, 80(9), 823–826. https://doi.org/10.1136/bjo.80.9.823
Page 59. Many terpenoids serve as.
349. Pichersky, E., & Raguso, R. A. (2018). Why do plants produce so many terpenoid compounds? New Phytologist, 220(3), 692–702. https://doi.org/10.1111/nph.14178
Page 60. Mono- and sesquiterpenes are volatile.
350. Seyfullah, L. J., Beimforde, C., Dal Corso, J., Perrichot, V., Rikkinen, J., & Schmidt, A. R. (2018). Production and preservation of resins – past and present. Biological Reviews, 93(3), 1684–1714. https://doi.org/10.1111/brv.12414
Page 60. The resin and essential oil.
351. Régimbal, J.-M., & Collin, G. (1994). Essential Oil Analysis of Balsam Fir Abies balsamea (L.) Mill. Journal of Essential Oil Research, 6(3), 229–238. https://doi.org/10.1080/10412905.1994.9698369
352. Mills, J. S., & White, R. (1977). Natural Resins of Art and Archaeology Their Sources, Chemistry, and Identification. Studies in Conservation, 22(1), 12–31. https://doi.org/10.2307/1505670
Page 60. The oldest amber.
353. Bray, P. S., & Anderson, K. B. (2009). Identification of Carboniferous (320 Million Years Old) Class Ic Amber. Science, 326(5949), 132–134. https://doi.org/10.1126/science.1177539
Page 60. There is even more ancient evidence. These references apply to the whole paragraph.
354. Hernick, L. V., Landing, E., & Bartowski, K. E. (2008). Earth’s oldest liverworts—Metzgeriothallus sharonae sp. nov. from the Middle Devonian (Givetian) of eastern New York, USA. Review of Palaeobotany and Palynology, 148(2–4), 154–162. https://doi.org/10.1016/j.revpalbo.2007.09.002
355. Labandeira, C. C., Tremblay, S. L., Bartowski, K. E., & VanAller Hernick, L. (2014). Middle Devonian liverwort herbivory and antiherbivore defence. New Phytologist, 202(1), 247–258. https://doi.org/10.1111/nph.12643
357. Howard, J. J., Cazin, J., & Wiemer, D. F. (1988). Toxicity of terpenoid deterrents to the leafcutting antAtta cephalotes and its mutualistic fungus. Journal of Chemical Ecology, 14(1), 59–69. https://doi.org/10.1007/BF01022531
358. Graham, L. E., Gray, J., Graham, L. E., & Gray, J. (2001). 8. The Origin, Morphology, and Ecophysiology of Early Embryophytes: Neontological and Paleontological Perspectives. In Plants Invade the Land (pp. 140–158). Columbia University Press. https://doi.org/10.7312/gens11160-009
359. Daeschler, E. B., Shubin, N. H., & Jenkins, F. A. (2006). A Devonian tetrapod-like fish and the evolution of the tetrapod body plan. Nature, 440(7085), 757–763. https://doi.org/10.1038/nature04639
Page 61. Pine sawfly caterpillars eat only.
360. Eisner, T., Johnessee, J. S., Carrel, J., Hendry, L. B., & Meinwald, J. (1974). Defensive Use by an Insect of a Plant Resin. Science, 184(4140), 996–999. https://doi.org/10.1126/science.184.4140.996
Page 61. If a predator tries to attack.
361. The Legend of Hot Tar or Pitch as a Defensive Weapon. Atzbach, R. (2015). Castles at War: The Danish Castle Research Association "Magt, Borg og Landskab" Interdisciplinary Symposium 2013. Atzbach, R., Meldgaard Sass Jensen, L. & Plith Lauritsen, L. (eds.). Bonn: Dr. Rudolf Habelt, p. 119-134 16 p. (Castles of the North, Vol. 1).
Page 61. To gain the upper hand.
362. Kelsey, R. G., Gallego, D., Sánchez-García, F. J., & Pajares, J. A. (2014). Ethanol accumulation during severe drought may signal tree vulnerability to detection and attack by bark beetles. Canadian Journal of Forest Research, 44(6), 554–561. https://doi.org/10.1139/cjfr-2013-0428
Page 61. But they do so in response to.
363. Kimmerer, T. W., & Kozlowski, T. T. (1982). Ethylene, Ethane, Acetaldehyde, and Ethanol Production By Plants under Stress. Plant Physiology, 69(4), 840–847. https://doi.org/10.1104/pp.69.4.840
Page 61. Once a mountain pine beetle.
364. Chiu, C. C., Keeling, C. I., & Bohlmann, J. (2018). Monoterpenyl esters in juvenile mountain pine beetle and sex-specific release of the aggregation pheromone trans -verbenol. Proceedings of the National Academy of Sciences, 115(14), 3652–3657. https://doi.org/10.1073/pnas.1722380115
Page 62. After all, why would.
365. Dawkins, R. (1976). The Selfish Gene. Oxford University Press
366. Alcock, J. (1982). Natural Selection and Communication among Bark Beetles. The Florida Entomologist, 65(1), 17–32. https://doi.org/10.2307/3494143
Page 62. When they bore into the trunk.
367. Safranyik, L., Wilson, B. & Others. (2007). The mountain pine beetle: a synthesis of biology, management and impacts on lodgepole pine. Canadian Forest Service.
Page 62. But there can be too much.
368. Raffa, K. F. (2014). Terpenes Tell Different Tales at Different Scales: Glimpses into the Chemical Ecology of Conifer - Bark Beetle - Microbial Interactions. Journal of Chemical Ecology, 40(1), 1–20. https://doi.org/10.1007/s10886-013-0368-y
Page 62. Bristlecone pines, including the 4,853.
369. Bentz, B. J., Hood, S. M., Hansen, E. M., Vandygriff, J. C., & Mock, K. E. (2017). Defense traits in the long‐lived Great Basin bristlecone pine and resistance to the native herbivore mountain pine beetle. New Phytologist, 213(2), 611–624. https://doi.org/10.1111/nph.14191
Page 62. From tree ring analyses.
370. Alfaro, R., Campbell, R., Vera, P., Hawkes, B., & Shore, T. (2004). Dendroecological Reconstruction of Mountain Pine Beetle Outbreaks in the Chilcotin Plateau of British Columbia. Mountain Pine Beetle Symposium: Challenges and Solutions 245–256 (Natural Resources Canada, Canadian Forest Service, Pac. For. Centre Victoria).
Page 62. For one tragic example.
371. EHS Today Staff. No One Knew He was There: Death in a Confined Space. https://www.ehstoday.com/safety/article/21904364/no-one-knew-he-was-there-death-in-a-confined-space (2002).
Page 63. Birch trees hold a special.
372. Ķencis, T. (2011). The Latvian Mythological Space in Scholarly Time. Archaeology, religion, and folklore in the Baltic Sea region, 144-157
374. Krasutsky, P. A. (2006). Birch bark research and development. Natural Product Reports, 23(6), 919. https://doi.org/10.1039/b606816b
Page 63. Known since 1788.
375. Lowitz, J. T. (1788). Über eine neue, fast benzoeartige Substanz der Birken. Chemische Annalen 2, 312–316.
Page 63. More recently, betulin.
376. Smith, P. F., Ogundele, A., Forrest, A., Wilton, J., Salzwedel, K., Doto, J., Allaway, G. P., & Martin, D. E. (2007). Phase I and II Study of the Safety, Virologic Effect, and Pharmacokinetics/Pharmacodynamics of Single-Dose 3- O -(3′,3′-Dimethylsuccinyl)Betulinic Acid (Bevirimat) against Human Immunodeficiency Virus Infection. Antimicrobial Agents and Chemotherapy, 51(10), 3574–3581. https://doi.org/10.1128/AAC.00152-07
Page 63. They protect the thin layer.
377. Harvey, R. B. (1923). Relation of the Color of Bark to the Temperature of the Cambium in Winter. Ecology, 4(4), 391–394. https://doi.org/10.2307/1929185
Page 64. Betulin also deters.
378. Bergvall, U. A., Co, M., Bergström, R., Sjöberg, P. J. R., Waldebäck, M., & Turner, C. (2013). Anti-browsing effects of birch bark extract on fallow deer. European Journal of Forest Research, 132(5–6), 717–725. https://doi.org/10.1007/s10342-013-0709-y
379. Hordyjewska, A., Ostapiuk, A., Horecka, A., & Kurzepa, J. (2019). Betulin and betulinic acid: triterpenoids derivatives with a powerful biological potential. Phytochemistry Reviews, 18(3), 929–951. https://doi.org/10.1007/s11101-019-09623-1
Page 64. Paper birch lines the roofs.
380. Turner, N. J., Ari, Y., Berkes, F., Davidson-Hunt, I., Ertug, Z. F., & Miller, A. (2009). Cultural Management of Living Trees: An International Perspective. Journal of Ethnobiology, 29(2), 237–270. https://doi.org/10.2993/0278-0771-29.2.237
382. Blessing F. K. (1977). The ojibway indians observed : papers of fred k. blessing jr. on the ojibway indians from the minnesota archaeologist. Minnesota Archaeological Society.
Page 65. Ethanol is unique.
383. Yang, J., Son, J. H., Kim, H., Cho, S., Na, J., Yeon, Y. J., & Lee, J. (2019). Mevalonate production from ethanol by direct conversion through acetyl-CoA using recombinant Pseudomonas putida, a novel biocatalyst for terpenoid production. Microbial Cell Factories, 18(1), 168. https://doi.org/10.1186/s12934-019-1213-y
Page 65. Despite my father’s AUD. The quote “good company, good welcome, good wine, can make good people.” is from William Shakespeare’s Henry the Eighth.
384. Shakespeare, W. Henry VIII. Published in Rafael Holinshed’s Chronicles of England, Scotlande, and Irelande 2, 1577.
Page 65. At the same time.
385. Baum-Baicker, C. (1985). The psychological benefits of moderate alcohol consumption: A review of the literature. Drug and Alcohol Dependence, 15(4), 305–322. https://doi.org/10.1016/0376-8716(85)90008-0
386. Marchand, A., Demers, A., Durand, P., & Simard, M. (2003). The moderating effect of alcohol intake on the relationship between work strains and psychological distress. Journal of Studies on Alcohol, 64(3), 419–427. https://doi.org/10.15288/jsa.2003.64.419
387. Stockwell, T., Zhao, J., Panwar, S., Roemer, A., Naimi, T., & Chikritzhs, T. (2016). Do “Moderate” Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality. J. Stud. Alcohol Drugs, 77(2), 185–198. https://doi.org/10.15288/jsad.2016.77.185
388. Griswold, M. G., Fullman, N., Hawley, C., Arian, N., Zimsen, S. R. M., Tymeson, H. D., Venkateswaran, V., Tapp, A. D., Forouzanfar, M. H., Salama, J. S., Abate, K. H., Abate, D., Abay, S. M., Abbafati, C., Abdulkader, R. S., Abebe, Z., Aboyans, V., Abrar, M. M., Acharya, P., … Gakidou, E. (2018). Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet, 392(10152), 1015–1035. https://doi.org/10.1016/S0140-6736(18)31310-2
389. John, U., Rumpf, H.-J., Hanke, M., & Meyer, C. (2021). Alcohol abstinence and mortality in a general population sample of adults in Germany: A cohort study. PLoS Med., 18(11), e1003819. https://doi.org/10.1371/journal.pmed.1003819
391. Kanny, D., Naimi, T. S., Liu, Y., Lu, H., & Brewer, R. D. (2018). Annual Total Binge Drinks Consumed by U.S. Adults, 2015. American Journal of Preventive Medicine, 54(4), 486–496. https://doi.org/10.1016/j.amepre.2017.12.021
Page 66. Brewer’s yeast, which humans.
392. Gonçalves, M., Pontes, A., Almeida, P., Barbosa, R., Serra, M., Libkind, D., Hutzler, M., Gonçalves, P., & Sampaio, J. P. (2016). Distinct Domestication Trajectories in Top-Fermenting Beer Yeasts and Wine Yeasts. Current Biology, 26(20), 2750–2761. https://doi.org/10.1016/j.cub.2016.08.040
393. McGovern, P. E., Zhang, J., Tang, J., Zhang, Z., Hall, G. R., Moreau, R. A., Nuñez, A., Butrym, E. D., Richards, M. P., Wang, C., Cheng, G., Zhao, Z., & Wang, C. (2004). Fermented beverages of pre- and proto-historic China. Proceedings of the National Academy of Sciences, 101(51), 17593–17598. https://doi.org/10.1073/pnas.0407921102
Page 66. Yeast’s ability to make alcohol. In addition to rotting fruit, these yeast associate with bark and galls in nature. The“Crabtree effect” is the observation that yeast ferment ethanol even in aerobic conditions, which is unusual for yeasts.
394. de Deken, R. H. (1966). The Crabtree Effect: A Regulatory System in Yeast. Journal of General Microbiology, 44(2), 149–156. https://doi.org/10.1099/00221287-44-2-149
395. Peter, J., de Chiara, M., Friedrich, A., Yue, J.-X., Pflieger, D., Bergström, A., Sigwalt, A., Barre, B., Freel, K., Llored, A., Cruaud, C., Labadie, K., Aury, J.-M., Istace, B., Lebrigand, K., Barbry, P., Engelen, S., Lemainque, A., Wincker, P., … Schacherer, J. (2018). Genome evolution across 1,011 Saccharomyces cerevisiae isolates. Nature, 556(7701), 339–344. https://doi.org/10.1038/s41586-018-0030-5
396. Piskur, J., Rozpedowska, E., Polakova, S., Merico, A., & Compagno, C. (2006). How did Saccharomyces evolve to become a good brewer? Trends in Genetics, 22(4), 183–186. https://doi.org/10.1016/j.tig.2006.02.002
397. Boynton, P. J., & Greig, D. (2014). The ecology and evolution of non-domesticated Saccharomyces species. Yeast, n/a-n/a. https://doi.org/10.1002/yea.3040
398. Pretorius, I. S. (2000). Tailoring wine yeast for the new millennium: novel approaches to the ancient art of winemaking. Yeast (Chichester, England), 16(8), 675–729. https://doi.org/10.1002/1097-0061(20000615)16:8<675::AID-YEA585>3.0.CO;2-B
399. Thomson, J. M., Gaucher, E. A., Burgan, M. F., de Kee, D. W., Li, T., Aris, J. P., & Benner, S. A. (2005). Resurrecting ancestral alcohol dehydrogenases from yeast. Nature Genetics, 37(6), 630–635. https://doi.org/10.1038/ng1553
Page 66. Brewer’s yeast is resistant.
400. Casey, G. P., & Ingledew, W. M. M. (1986). Ethanol Tolerance in Yeasts. CRC Critical Reviews in Microbiology, 13(3), 219–280. https://doi.org/10.3109/10408418609108739
401. Snoek, T., Verstrepen, K. J., & Voordeckers, K. (2016). How do yeast cells become tolerant to high ethanol concentrations? Current Genetics, 62(3), 475–480. https://doi.org/10.1007/s00294-015-0561-3
402. Williams, K. M., Liu, P., & Fay, J. C. (2015). Evolution of ecological dominance of yeast species in high‐sugar environments. Evolution, 69(8), 2079–2093. https://doi.org/10.1111/evo.12707
Page 67. Unsurprisingly, fruit flies are resistant.
403. McKenzie, J. A., & Parsons, P. A. (1972). Alcohol tolerance: An ecological parameter in the relative success of Drosophila melanogaster and Drosophila simulans. Oecologia, 10(4), 373–388. https://doi.org/10.1007/BF00345738
Page 67. If that doesn’t work.
404. Milan, N. F., Kacsoh, B. Z., & Schlenke, T. A. (2012). Alcohol Consumption as Self-Medication against Blood-Borne Parasites in the Fruit Fly. Current Biology, 22(6), 488–493. https://doi.org/10.1016/j.cub.2012.01.045
Page 67. They only do so if.
405. Kacsoh, B. Z., Lynch, Z. R., Mortimer, N. T., & Schlenke, T. A. (2013). Fruit Flies Medicate Offspring After Seeing Parasites. Science, 339(6122), 947–950. https://doi.org/10.1126/science.1229625
Page 68. The cost of a high ethanol.
406. Chawla, S. S., Perron, J.-M., & Radouco-Thomas, C. (1981). Effects of ingested ethanol on adult Drosophila melanogaster (Diptera: Drosophilidae). The Canadian Entomologist, 113(4), 315–323. https://doi.org/10.4039/Ent113315-4
Page 69. We know Darwin held this view. The quote is derived from the letter cited below.
407. Darwin, C., & The Editors of the Darwin Correspondence Project. (2021). The Correspondence of Charles Darwin (F. Burkhardt & J. A. Secord, Eds.). Cambridge University Press. https://doi.org/10.1017/9781108884594
Page 69. Ethanol is thought to.
408. Kumar, S., Porcu, P., Werner, D. F., Matthews, D. B., Diaz-Granados, J. L., Helfand, R. S., & Morrow, A. L. (2009). The role of GABAA receptors in the acute and chronic effects of ethanol: a decade of progress. Psychopharmacology, 205(4), 529–564. https://doi.org/10.1007/s00213-009-1562-z
Page 69. It may actually bind to the.
409. Wallner, M., Hanchar, H. J., & Olsen, R. W. (2014). Alcohol Selectivity of β3-Containing GABAA Receptors: Evidence for a Unique Extracellular Alcohol/Imidazobenzodiazepine Ro15-4513 Binding Site at the α+β- Subunit Interface in αβ3δ GABAA Receptors. Neurochemical Research, 39(6), 1118–1126. https://doi.org/10.1007/s11064-014-1243-0
410. Masiulis, S., Desai, R., Uchański, T., Serna Martin, I., Laverty, D., Karia, D., Malinauskas, T., Zivanov, J., Pardon, E., Kotecha, A., Steyaert, J., Miller, K. W., & Aricescu, A. R. (2019). GABAA receptor signalling mechanisms revealed by structural pharmacology. Nature, 565(7740), 454–459. https://doi.org/10.1038/s41586-018-0832-5
411. Laverty, D., Desai, R., Uchański, T., Masiulis, S., Stec, W. J., Malinauskas, T., Zivanov, J., Pardon, E., Steyaert, J., Miller, K. W., & Aricescu, A. R. (2019). Cryo-EM structure of the human α1β3γ2 GABAA receptor in a lipid bilayer. Nature, 565(7740), 516–520. https://doi.org/10.1038/s41586-018-0833-4
Page 70. In addition to coping with physical trauma.
413. Smith, K. Z., Smith, P. H., & Grekin, E. R. (2014). Childhood sexual abuse, distress, and alcohol-related problems: Moderation by drinking to cope. Psychology of Addictive Behaviors, 28(2), 532–537. https://doi.org/10.1037/a0035381
Page 70. Robert Dudley, my UC-Berkeley colleague. References support the paragraphs through the end of this section on page 71.
414. Dudley, R. (2000). Evolutionary Origins of Human Alcoholism in Primate Frugivory. The Quarterly Review of Biology, 75(1), 3–15. https://doi.org/10.1086/393255
415. Dudley, R. (2002). Fermenting fruit and the historical ecology of ethanol ingestion: is alcoholism in modern humans an evolutionary hangover? Addiction, 97(4), 381–388. https://doi.org/10.1046/j.1360-0443.2002.00002.x
416. Stephens, Dustin, and Robert K. Dudley. (2004). The drunken monkey hypothesis. Natural History
417. Dudley, Robert. (2014.) The drunken monkey: why we drink and abuse alcohol. Univ of California Press
418. Dudley, R. (2004). Ethanol, Fruit Ripening, and the Historical Origins of Human Alcoholism in Primate Frugivory. Integrative and Comparative Biology, 44(4), 315–323. https://doi.org/10.1093/icb/44.4.315
419. Sánchez, F., Korine, C., Pinshow, B., & Dudley, R. (2004). The Possible Roles of Ethanol in the Relationship Between Plants and Frugivores: First Experiments with Egyptian Fruit Bats1. Integrative and Comparative Biology, 44(4), 290–294. https://doi.org/10.1093/icb/44.4.290
421. Campbell, C. J., Maro, A., Weaver, V., & Dudley, R. (2022). Dietary ethanol ingestion by free-ranging spider monkeys (Ateles geoffroyi ). Royal Society Open Science, 9(3). https://doi.org/10.1098/rsos.211729
Page 71. We know now, thanks largely.
422. Li, Qing.(2018). Shirin-Yoku: The Art and Science of Forest Bathing. Penguin.
423. Li, Q., Kobayashi, M., Wakayama, Y., Inagaki, H., Katsumata, M., Hirata, Y., Hirata, K., Shimizu, T., Kawada, T., Park, B. J., Ohira, T., Kagawa, T., & Miyazaki, Y. (2009). Effect of Phytoncide from Trees on Human Natural Killer Cell Function. International Journal of Immunopathology and Pharmacology, 22(4), 951–959. https://doi.org/10.1177/039463200902200410
Page 71. In a study of 92 alcoholics.
424. Kuria, M. W., Ndetei, D. M., Obot, I. S., Khasakhala, L. I., Bagaka, B. M., Mbugua, M. N., & Kamau, J. (2012). The Association between Alcohol Dependence and Depression before and after Treatment for Alcohol Dependence. ISRN Psychiatry, 2012, 1–6. https://doi.org/10.5402/2012/482802
425. Shin, W. S., Shin, C. S., & Yeoun, P. S. (2012). The influence of forest therapy camp on depression in alcoholics. Environmental Health and Preventive Medicine, 17(1), 73–76. https://doi.org/10.1007/s12199-011-0215-0
Page 71. We don’t know for certain.
426. Antonelli, M., Donelli, D., Carlone, L., Maggini, V., Firenzuoli, F., & Bedeschi, E. (2022). Effects of forest bathing (shinrin-yoku) on individual well-being: an umbrella review. International Journal of Environmental Health Research, 32(8), 1842–1867. https://doi.org/10.1080/09603123.2021.1919293
Page 72. However, as Qing Li.
427. Li, Qing. (2018). Shirin-Yoku: The Art and Science of Forest Bathing. Penguin.
Page 72. One ideafor the mechanism.
428. Yamaoka, S., Tomita, T., Imaizumi, Y., Watanabe, K., & Hatanaka, A. (2005). Effects of plant-derived odors on sleep-wakefulness and circadian rhythmicity in rats. Chemical senses, 30 Suppl 1, i264–i265. https://doi.org/10.1093/chemse/bjh216
Page 72. Most likely, plants.
429. Bown, A. W., MacGregor, K. B., & Shelp, B. J. (2006). Gamma-aminobutyrate: defense against invertebrate pests? Trends in Plant Science, 11(9), 424–427. https://doi.org/10.1016/j.tplants.2006.07.002
Page 72. With my collaborator Jia Huang.
430. Guo, L., Qiao, X., Haji, D., Zhou, T., Liu, Z., Whiteman, N. K., & Huang, J. (2023). Convergent resistance to GABA receptor neurotoxins through plant–insect coevolution. Nature Ecology & Evolution, 7(9), 1444–1456. https://doi.org/10.1038/s41559-023-02127-4
Page 72. The neurotransmitter GABA.
431. Dudel, J., Gryder, R., Kaji, A., Kuffler, S. W., & Potter, D. D. (1963). Gama-aminobutyric acid and other blocking compounds in Crustacea. I. Central nervous system. Journal of Neurophysiology, 26(5), 721–728. https://doi.org/10.1152/jn.1963.26.5.721
Page 72. They use it much as they.
432. Bown, A. W., MacGregor, K. B., & Shelp, B. J. (2006). Gamma-aminobutyrate: defense against invertebrate pests? Trends in Plant Science, 11(9), 424–427. https://doi.org/10.1016/j.tplants.2006.07.002
Page 72. Alpha pinene causes a hypnotic effect.
433. Satou, T., Kasuya, H., Maeda, K., & Koike, K. (2014). Daily Inhalation of α‐Pinene in Mice: Effects on Behavior and Organ Accumulation. Phytotherapy Research, 28(9), 1284–1287. https://doi.org/10.1002/ptr.5105
Page 72 and 73. All things considered.
434. Oh, B., Lee, K. J., Zaslawski, C., Yeung, A., Rosenthal, D., Larkey, L., & Back, M. (2017). Health and well-being benefits of spending time in forests: systematic review. Environmental Health and Preventive Medicine, 22(1), 71. https://doi.org/10.1186/s12199-017-0677-9
Page 73. In the forest bathing literature.
435. Kohman, E. F. (1947). The Chemical Components of Onion Vapors Responsible for Wound-healing Qualities. Science, 106(2765), 625–627. https://doi.org/10.1126/science.106.2765.625
Page 73. Unfortunately, Tokin aligned himself with Lysenkoism.
436. Dobzhansky, T. (1955). The Crisis of Soviet Biology. In Continuity and Change in Russian and Soviet Thought (pp. 329–346). Harvard University Press. https://doi.org/10.4159/harvard.9780674367173.c25
Page 73. Although his reasoning was incorrect.
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Page 73. He also presciently hypothesized.
438. Baldwin, I. T., & Schultz, J. C. (1983). Rapid Changes in Tree Leaf Chemistry Induced by Damage: Evidence for Communication Between Plants. Science, 221(4607), 277–279. https://doi.org/10.1126/science.221.4607.277
439. Rhoades, D. F. (1983). Responses of Alder and Willow to Attack by Tent Caterpillars and Webworms: Evidence for Pheromonal Sensitivity of Willows (pp. 55–68). https://doi.org/10.1021/bk-1983-0208.ch004
440. Kazarian, R. (1983). Some Evidence That Trees ‘Communicate When in Trouble.’ Environmental Conservation, 10(2), 173–173. https://doi.org/10.1017/S0376892900012376
Page 73. These messages can even be absorbed.
441. Himanen, S. J., Blande, J. D., Klemola, T., Pulkkinen, J., Heijari, J., & Holopainen, J. K. (2010). Birch ( Betula spp.) leaves adsorb and re‐release volatiles specific to neighbouring plants – a mechanism for associational herbivore resistance? New Phytologist, 186(3), 722–732. https://doi.org/10.1111/j.1469-8137.2010.03220.x
442. Baldwin, I. T., & Schultz, J. C. (1983). Rapid Changes in Tree Leaf Chemistry Induced by Damage: Evidence for Communication Between Plants. Science, 221(4607), 277–279. https://doi.org/10.1126/science.221.4607.277
Page 73. We now know.
443. Karban, R., Shiojiri, K., Huntzinger, M., & McCall, A. C. (2006). Damage-induced resistance in sagebrush: volatiles are key to intra- and interplant communication. Ecology, 87(4), 922–930. https://doi.org/10.1890/0012-9658(2006)87[922:drisva]2.0.co;2
444. Karban, R., Shiojiri, K., Ishizaki, S., Wetzel, W. C., & Evans, R. Y. (2013). Kin recognition affects plant communication and defence. Proceedings of the Royal Society B: Biological Sciences, 280(1756), 20123062. https://doi.org/10.1098/rspb.2012.3062
Page 74. Parasitoid wasps, for example.
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Page 75. However, beultin, like alpha-pinene.
446. Muceniece, R., Saleniece, K., Rumaks, J., Krigere, L., Dzirkale, Z., Mezhapuke, R., Zharkova, O., & Klusa, V. (2008). Betulin binds to gamma-aminobutyric acid receptors and exerts anticonvulsant action in mice. Pharmacol. Biochem. Behav., 90(4), 712–716. https://doi.org/10.1016/j.pbb.2008.05.015
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Page 75. Additionally, naturally occurring.
449. Olfson, E., & Bierut, L. J. (2012). Convergence of genome-wide association and candidate gene studies for alcoholism. Alcohol. Clin. Exp. Res., 36(12), 2086–2094. https://doi.org/10.1111/j.1530-0277.2012.01843.x
450. Li, D., Sulovari, A., Cheng, C., Zhao, H., Kranzler, H. R., & Gelernter, J. (2014). Association of gamma-aminobutyric acid A receptor α2 gene (GABRA2) with alcohol use disorder. Neuropsychopharmacology, 39(4), 907–918. https://doi.org/10.1038/npp.2013.291
Page 76. Fog drip brings life.
451. Limm, E. B., Simonin, K. A., Bothman, A. G., & Dawson, T. E. (2009). Foliar water uptake: a common water acquisition strategy for plants of the redwood forest. Oecologia, 161(3), 449–459. https://doi.org/10.1007/s00442-009-1400-3
Page 76. Toxins produced by the leaves.
452. del Moral, R., & Muller, C. H. (1969). Fog Drip: A Mechanism of Toxin Transport from Eucalyptus globulus. Bulletin of the Torrey Botanical Club, 96(4), 467. https://doi.org/10.2307/2484065 453. Molina, A., Reigosa, M. J., & Carballeira, A. (1991). Release of allelochemical agents from litter, throughfall, and topsoil in plantations of Eucalyptus globulus Labill in Spain. Journal of Chemical Ecology, 17(1), 147–160. https://doi.org/10.1007/BF00994428
455. del Moral, R., & Muller, C. H. (1970). The Allelopathic Effects of Eucalyptus camaldulensis. American Midland Naturalist, 83(1), 254. https://doi.org/10.2307/2424020
457. Becerra, P. I., Catford, J. A., Inderjit, Luce McLeod, M., Andonian, K., Aschehoug, E. T., Montesinos, D., & Callaway, R. M. (2018). Inhibitory effects of Eucalyptus globulus on understorey plant growth and species richness are greater in non‐native regions. Global Ecology and Biogeography, 27(1), 68–76. https://doi.org/10.1111/geb.12676
Page 77. Nowadays, eucalyptol is used.
458. Galan, D. M., Ezeudu, N. E., Garcia, J., Geronimo, C. A., Berry, N. M., & Malcolm, B. J. (2020). Eucalyptol (1,8-cineole): an underutilized ally in respiratory disorders? Journal of Essential Oil Research, 32(2), 103–110. https://doi.org/10.1080/10412905.2020.1716867
Page 77. In Australia, suspected eucalyptol poisoning.
459. Day, L. M., Ozanne-Smith, J., Parsons, B. J., Dobbin, M., & Tibballs, J. (1997). Eucalyptus oil poisoning among young children: mechanisms of access and the potential for prevention. Australian and New Zealand Journal of Public Health, 21(3), 297–302. https://doi.org/10.1111/j.1467-842X.1997.tb01703.x
461. Tibballs, J. (1995). Clinical effects and management of eucalyptus oil ingestion in infants and young children. Medical Journal of Australia, 163(4), 177–180. https://doi.org/10.5694/j.1326-5377.1995.tb124516.x
463. Goto, S., Suzuki, H., Nakagawa, T., & Shimizu, K. (2020). The Effect of Eucalyptol on Nursing Home Residents. Scientific Reports, 10(1), 3996. https://doi.org/10.1038/s41598-020-61045-8
Page 78. Blood flow throughout.
464. Našel, C., Našel, B., Samec, P., Schindler, E., & Buchbauer, G. (1994). Functional imaging of effects of fragrances on the human brain after prolonged inhalation. Chemical Senses, 19(4), 359–364. https://doi.org/10.1093/chemse/19.4.359
465. Gomes, P. B., Feitosa, M. L., Silva, M. I. G., Noronha, E. C., Moura, B. A., Venâncio, E. T., Rios, E. R. V., de Sousa, D. P., de Vasconcelos, S. M. M., Fonteles, M. M. de F., & de Sousa, F. C. F. (2010). Anxiolytic-like effect of the monoterpene 1,4-cineole in mice. Pharmacology Biochemistry and Behavior, 96(3), 287–293. https://doi.org/10.1016/j.pbb.2010.05.019
Page 78. Eucalyptol activates the “menthol receptor.”
466. Takaishi, M., Fujita, F., Uchida, K., Yamamoto, S., Sawada (Shimizu), M., Hatai (Uotsu), C., Shimizu, M., & Tominaga, M. (2012). 1,8-Cineole, a TRPM8 Agonist, is a Novel Natural Antagonist of Human TRPA1. Molecular Pain, 8, 1744-8069-8–86. https://doi.org/10.1186/1744-8069-8-86
467. Bautista, D. M., Siemens, J., Glazer, J. M., Tsuruda, P. R., Basbaum, A. I., Stucky, C. L., Jordt, S.-E., & Julius, D. (2007). The menthol receptor TRPM8 is the principal detector of environmental cold. Nature, 448(7150), 204–208. https://doi.org/10.1038/nature05910
Page 78. Plants don’t always use.
468. Ramya, M., Jang, S., An, H.-R., Lee, S.-Y., Park, P.-M., & Park, P. H. (2020). Volatile Organic Compounds from Orchids: From Synthesis and Function to Gene Regulation. International Journal of Molecular Sciences, 21(3), 1160. https://doi.org/10.3390/ijms21031160
469. Brand, P., Hinojosa-Díaz, I. A., Ayala, R., Daigle, M., Yurrita Obiols, C. L., Eltz, T., & Ramírez, S. R. (2020). The evolution of sexual signaling is linked to odorant receptor tuning in perfume-collecting orchid bees. Nature Communications, 11(1), 244. https://doi.org/10.1038/s41467-019-14162-6
471. Stephenson, A. G. (1981). Toxic Nectar Deters Nectar Thieves of Catalpa speciosa. American Midland Naturalist, 105(2), 381. https://doi.org/10.2307/2424757
472. Rhoades, D. F., & Bergdahl, J. C. (1981). Adaptive Significance of Toxic Nectar. The American Naturalist, 117(5), 798–803. https://doi.org/10.1086/283765
473. Stephenson, A. G. (1982). Iridoid glycosides in the nectar of Catalpa speciosa are unpalatable to nectar thieves. Journal of Chemical Ecology, 8(7), 1025–1034. https://doi.org/10.1007/BF00987883
475. Shrestha, M., Dyer, A. G., Boyd‐Gerny, S., Wong, B. B. M., & Burd, M. (2013). Shades of red: bird‐pollinated flowers target the specific colour discrimination abilities of avian vision. New Phytologist, 198(1), 301–310. https://doi.org/10.1111/nph.12135
478. Botes, C., Johnson, S. D., & Cowling, R. M. (2009). The Birds and the Bees: Using Selective Exclusion to Identify Effective Pollinators of African Tree Aloes. International Journal of Plant Sciences, 170(2), 151–156. https://doi.org/10.1086/595291
480. Tiedeken, E. J., Egan, P. A., Stevenson, P. C., Wright, G. A., Brown, M. J. F., Power, E. F., Farrell, I., Matthews, S. M., & Stout, J. C. (2016). Nectar chemistry modulates the impact of an invasive plant on native pollinators. Functional Ecology, 30(6), 885–893. https://doi.org/10.1111/1365-2435.12588
Page 81. Notably, the Green historian Strabo. The quote below this paragraph is derived from this reference as well.
482. Mayor, A. (2010). The Poison King: The Life and Legend of Mithradates, Rome’s Deadliest Enemy. Princeton University Press. http://www.jstor.org/stable/j.ctt7t7kz
Page 81. The poison honey may well be.
483. Koca, I., & Koca, A. F. (2007). Poisoning by mad honey: A brief review. Food and Chemical Toxicology, 45(8), 1315–1318. https://doi.org/10.1016/j.fct.2007.04.006
486. Strickland, S. S. (1982). Honey Hunting by the Gurungs of Nepal. Bee World, 63(4), 153–161. https://doi.org/10.1080/0005772X.1982.11097889 487. Shrestha, T. M., Nepal, G., Shing, Y. K., & Shrestha, L. (2018). Cardiovascular, psychiatric, and neurological phenomena seen in mad honey disease: A clinical case report. Clinical Case Reports, 6(12), 2355–2357. https://doi.org/10.1002/ccr3.1889 488. Pant, K. (2018). Mad honey: food, medicine or toxin? A food technology perspective. Journal of Agriculture and Environment, 19, 51-58.
491. Lange, B. M., & Conner, C. F. (2021). Taxanes and taxoids of the genus Taxus – A comprehensive inventory of chemical diversity. Phytochemistry, 190, 112829. https://doi.org/10.1016/j.phytochem.2021.112829
Page 82. The compound showed promise.
492. Fuchs, D. A., & Johnson, R. K. (1978). Cytologic evidence that taxol, an antineoplastic agent from Taxus brevifolia, acts as a mitotic spindle poison. Cancer Treatment Reports, 62(8), 1219–1222.
493. Rowinsky EK, Donehower RC, Rosenshein NB, Ettinger DS, McGuire WP (1988). Phase II study of taxol in advanced epithelial malignancies. Proceedings of the Association of Clinical Oncology. 7: 136.
494. Wani, M. C., Taylor, H. L., Wall, M. E., Coggon, P., & McPhail, A. T. (1971). Plant antitumor agents. VI. Isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. Journal of the American Chemical Society, 93(9), 2325–2327. https://doi.org/10.1021/ja00738a045
495. Wall, M. E., & Wani, M. C. (1995). Camptothecin and taxol: discovery to clinic--thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Research, 55(4), 753–760.
Regarding the age of the bog, see this quote (“The peat at the bog site is approximately 3.5 m deep with a basal radiocarbon date of 10040 ± 70 yr BP.”) from:
500. Weltzin, J. F., Bridgham, S. D., Pastor, J., Chen, J., & Harth, C. (2003). Potential effects of warming and drying on peatland plant community composition. Global Change Biology, 9(2), 141–151. https://doi.org/https://doi.org/10.1046/j.1365-2486.2003.00571.x
503. Combs, A. B., & Acosta, D. (1990). Toxic mechanisms of the heart: a review. Toxicologic Pathology, 18(4 Pt 1), 583–596.
Page 84. It turns out that. Note that in addition to emetine, cephaeline is another alkaloid from the same plants that may even be more emetic and responsible for the emesis.
504. Lee, M. R. (2008). Ipecacuanha: the South American vomiting root. The Journal of the Royal College of Physicians of Edinburgh, 38(4), 355–360.
505. Rosales-López, Catalina, Muñoz-Arrieta, Rodrigo, & Abdelnour-Esquivel, Ana. (2020). Emetine and cephaeline content in plants of Psychotria ipecacuanha in Costa Rica. Revista Colombiana de Química, 49(2), 18-22. https://doi.org/10.15446/rev.colomb.quim.v49n2.78347
507. Rogers, L. (1912). The rapid cure of amoebic dysentery and hepatitis by hypodermic injections of soluble salts of emetine. British Medical Journal, 1(2686), 1424–1425. https://doi.org/10.1136/bmj.1.2686.1424
508. Bleasel, M. D., & Peterson, G. M. (2020). Emetine Is Not Ipecac: Considerations for Its Use as Treatment for SARS-CoV2. Pharmaceuticals (Basel, Switzerland), 13(12). https://doi.org/10.3390/ph13120428
511. PURCHAS, S. (1311) His pilgrimes, vol. IV, London , 1625-26.
512. Grollman, A. P., & Jarkovsky, Z. (1975). Emetine and Related Alkaloids. In J. W. Corcoran, F. E. Hahn, J. F. Snell, & K. L. Arora (Eds.), Mechanism of Action of Antimicrobial and Antitumor Agents (pp. 420–435). Springer Berlin Heidelberg. https://doi.org/10.1007/978-3-642-46304-4_27
Page 85. Nowadays, however, it is a dysentery.
513. Combs, A. B., & Acosta, D. (1990). Toxic mechanisms of the heart: a review. Toxicologic Pathology, 18(4 Pt 1), 583–596.
Page 85. As we’ve seen with other bright.
514. Brower, L. P., van Brower, J., & Corvino, J. M. (1967). Plant poisons in a terrestrial food chain. Proceedings of the National Academy of Sciences of the United States of America, 57(4), 893–898. https://doi.org/10.1073/pnas.57.4.893
515. Brower, L. P., Ryerson, W. N., Coppinger, L. L., & Glazier, S. C. (1968). Ecological chemistry and the palatability spectrum. Science (New York, N.Y.), 161(3848), 1349–1350. https://doi.org/10.1126/science.161.3848.1349
517. Agrawal, A. A., Petschenka, G., Bingham, R. A., Weber, M. G., & Rasmann, S. (2012). Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions. The New Phytologist, 194(1), 28–45. https://doi.org/10.1111/j.1469-8137.2011.04049.x
Page 86. The insects then stored the toxins in their bodies.
519. Reichstein, T., von Euw, J., Parsons, J. A., & Rothschild, M. (1968). Heart poisons in the monarch butterfly. Some aposematic butterflies obtain protection from cardenolides present in their food plants. Science (New York, N.Y.), 161(3844), 861–866. https://doi.org/10.1126/science.161.3844.861
Page 86. The “golden diadem” reference is from Miriam Rothschild when she was describing monarch butterflies and their migration from eastern North America to the oyamel fir forests of Mexico:
521. PARSONS, J. A. (1965). A DIGITALIS-LIKE TOXIN IN THE MONARCH BUTTERFLY, DANAUS PLEXIPPUS L. The Journal of Physiology, 178(2), 290–304. https://doi.org/10.1113/jphysiol.1965.sp007628
522. Reichstein, T., von Euw, J., Parsons, J. A., & Rothschild, M. (1968). Heart poisons in the monarch butterfly. Some aposematic butterflies obtain protection from cardenolides present in their food plants. Science (New York, N.Y.), 161(3844), 861–866. https://doi.org/10.1126/science.161.3844.861
523. Brower, L. P., Ryerson, W. N., Coppinger, L. L., & Glazier, S. C. (1968). Ecological chemistry and the palatability spectrum. Science (New York, N.Y.), 161(3848), 1349–1350. https://doi.org/10.1126/science.161.3848.1349
Page 88. One of the principal toxins.
524. Cheung, H. T. A., Watson, T. R., Lee, S. M., McChesney, M. M., & Seiber, J. N. (1986). Structure of aspecioside from the monarch butterfly larvae foodplants Asclepias speciosa and A. syriaca. Journal of the Chemical Society, Perkin Transactions 1, 0, 61–65. https://doi.org/10.1039/P19860000061
526. Züst, T., Mirzaei, M. & Jander, G. (2018). Erysimum cheiranthoides, an ecological research system with potential as a genetic and genomic model for studying cardiac glycoside biosynthesis. Phytochem Rev 17, 1239–1251. https://doi.org/10.1007/s11101-018-9562-4
527. Eisner, T., Wiemer, D. F., Haynes, L. W., & Meinwald, J. (1978). Lucibufagins: Defensive steroids from the fireflies Photinus ignitus and P. marginellus (Coleoptera: Lampyridae). Proceedings of the National Academy of Sciences of the United States of America, 75(2), 905–908. https://doi.org/10.1073/pnas.75.2.905
Page. 87. In Madagascar.
528. Campbell, G. (1991). The State and Pre-Colonial Demographic History: The Case of Nineteenth-Century Madagascar. The Journal of African History, 32(3), 415–445. https://doi.org/DOI: 10.1017/S0021853700031534
532. Brower, J. V. Z. (1960). Experimental Studies of Mimicry. IV. The Reactions of Starlings to Different Proportions of Models and Mimics. The American Naturalist, 94(877), 271–282. https://doi.org/10.1086/282128
533. Allen, W., Ruxton, G., Sherratt, T., & Speed, M. (2018). Avoiding Attack: The Evolutionary Ecology of Crypsis, Aposematism, and Mimicry. Oxford: Oxford University Press.
534. Müller, F. (1878). Über die vortheile der mimicry bei schmetterlingen.
Page 87. The toxic channel of communication that flows.
535. Agrawal, A. (2017). Monarchs and Milkweed: A Migrating Butterfly, a Poisonous Plant, and Their Remarkable Story of Coevolution. Princeton University Press. https://doi.org/10.2307/j.ctvc775wc
Page 87. But the milkweeds can’t uproot themselves.
537. SCHATZMANN & H. J. (1953). Herzglykoside als Hemmstoffe fur den activen Kalium und Natrium-Transport durch die Erythrocytemembran. Helv. Physiol. Pharmacol. Acta 11, 346–354
Page 88. Nearly forty years later.
538. 2023. Jens C. Skou – Biographical. NobelPrize.org. Nobel Prize Outreach https://www.nobelprize.org/prizes/chemistry/1997/skou/facts/
Page 88. Skou found that the cardiac.
539. Skou, J. Chr. (1960). Further investigations on a Mg++ + Na+-activated adenosintriphosphatase, possibly related to the active, linked transport of Na+ and K+ across the nerve membrane. Biochimica et Biophysica Acta, 42, 6–23. https://doi.org/https://doi.org/10.1016/0006-3002(60)90746-0
Page 88. The bulb of the sea squill.
540. Gentry, H. S., Verbiscar, A. J., & Banigan, T. F. (1987). Red squill (Urginea maritima, Liliaceae). Economic Botany, 41(2), 267–282. https://doi.org/10.1007/BF02858974
Page 88. The plant has been used.
541. Stannard, J. (1974). Squill in ancient and medieval materia medica, with special reference to its employment for dropsy. Bulletin of the New York Academy of Medicine, 50(6), 684–713.
Quote from: 542. Celsus: De Medicina. With an english translation by W. G. Spencer, M.S. (Lond.), F.R.C.S. (Eng.). In three volumes (Loeb Classical Library). 6 5/8 × 4 1/4 in. Vol. I (1935).
Page 90. As digoxin became the drug of choice. Note that the image of Mother Hutton handing the recipe to William Withering was created on January 1, 1928 by William Meade Prince.
544. Krikler, D. M. (1985). Withering and the foxglove: the making of a myth. British Heart Journal, 54(3), 256–257. https://doi.org/10.1136/hrt.54.3.256
Page 90. It remains of the World Health Organization’s.
546. Web Annex A. World Health Organization Model List of Essential Medicines – 23rd List, 2023. In: The selection and use of essential medicines 2023: Executive summary of the report of the 24th WHO Expert Committee on the Selection and Use of Essential Medicines, 24 – 28 April 2023. Geneva: World Health Organization; 2023 https://www.who.int/publications/i/item/WHO-MHP-HPS-EML-2023.02
Page 90. Another important cardiac glycoside.
547. Osseo-Asare, A. D. (2008). Bioprospecting and Resistance: Transforming Poisoned Arrows into Strophantin Pills in Colonial Gold Coast, 1885–1922. Social History of Medicine, 21(2), 269–290. https://doi.org/10.1093/shm/hkn025
Page 90. Europeans actually first directly. Note that utsungu is the word for bitterness in Digo and is the name for the arrow poison derived from the poison arrow tree species Acokanthera schimperi, which contains is ouabain.
551. Neuwinger, H. D. (1996). African Ethnobotany: Poisons and Drugs : Chemistry, Pharmacology, Toxicology. CRC Press. https://doi.org/10.1021/np960638h
552. Theal, G.M. (1907) History and Ethnography of Africa South of the Zambesi – Vol. I, The Portuguese in South Africa from 1505 to 1700 London: Sonneschein.
Page 90. Similarly, Indigenous peoples of.
553. Shrestha, T., Kopp, B., & Bisset, N. G. (1992). The Moraceae-based dart poisons of South America. Cardiac glycosides of Maquira and Naucleopsis species. Journal of Ethnopharmacology, 37(2), 129–143. https://doi.org/10.1016/0378-8741(92)90071-x
554. Kopp, B., Bauer, W. P., & Bernkop-Schnürch, A. (1992). Analysis of some Malaysian dart poisons. Journal of Ethnopharmacology, 36(1), 57–62. https://doi.org/10.1016/0378-8741(92)90061-u
556. Kingdon, J., Agwanda, B., Kinnaird, M., O’Brien, T., Holland, C., Gheysens, T., Boulet-Audet, M., & Vollrath, F. (2012). A poisonous surprise under the coat of the African crested rat. Proceedings. Biological Sciences, 279(1729), 675–680. https://doi.org/10.1098/rspb.2011.1169
See also (toad-annointing hedgehogs and firefly-eating snakes):
557. Brodie, E. D. (1977). Hedgehogs use toad venom in their own defence. Nature, 268(5621), 627–628. https://doi.org/10.1038/268627a0
558. Yoshida, T., Ujiie, R., Savitzky, A. H., Jono, T., Inoue, T., Yoshinaga, N., Aburaya, S., Aoki, W., Takeuchi, H., Ding, L., Chen, Q., Cao, C., Tsai, T.-S., Silva, A. de, Mahaulpatha, D., Nguyen, T. T., Tang, Y., Mori, N., & Mori, A. (2020). Dramatic dietary shift maintains sequestered toxins in chemically defended snakes. Proceedings of the National Academy of Sciences of the United States of America, 117(11), 5964–5969. https://doi.org/10.1073/pnas.1919065117
Page 91. I was fortunate enough.
559. Dobler, S., Dalla, S., Wagschal, V., & Agrawal, A. A. (2012). Community-wide convergent evolution in insect adaptation to toxic cardenolides by substitutions in the Na, K-ATPase. Proceedings of the National Academy of Sciences, 109(32), 13040–13045. https://www.pnas.org/content/109/32/13040.short
560. Zhen, Y., Aardema, M. L., Medina, E. M., Schumer, M., & Andolfatto, P. (2012). Parallel Molecular Evolution in an Herbivore Community. Science. https://doi.org/10.1126/science.1226630
Page 91. In the end, after eight years.
561. Karageorgi, M., Groen, S. C., Sumbul, F., Pelaez, J. N., Verster, K. I., Aguilar, J. M., Hastings, A. P., Bernstein, S. L., Matsunaga, T., Astourian, M., Guerra, G., Rico, F., Dobler, S., Agrawal, A. A., & Whiteman, N. K. (2019). Genome editing retraces the evolution of toxin resistance in the monarch butterfly. Nature, 574(7778), 409–412. https://doi.org/10.1038/s41586-019-1610-8
Page 92. In 1981.
562. Fink, L. S., & Brower, L. P. (1981). Birds can overcome the cardenolide defence of monarch butterflies in Mexico. Nature, 291(5810), 67–70. https://doi.org/10.1038/291067a0
563. Fink, L. S., Brower, L. P., Waide, R. B., & Spitzer, P. R. (1983). Overwintering Monarch Butterflies as Food for Insectivorous Birds in Mexico. Biotropica, 15(2), 151–153. https://doi.org/10.2307/2387962
Page 92. In 2021, Niels wrote to me.
564. Groen, S. C., & Whiteman, N. K. (2021). Convergent evolution of cardiac-glycoside resistance in predators and parasites of milkweed herbivores. Curr. Biol., 31(22), R1465–R1466. https://doi.org/10.1016/j.cub.2021.10.025
Page 92. Cardiac glycosides can bind to the sodium pump.
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Page 93. Such blocking can be achieved by only. However, it may be that there are sites outside of the binding pocket that can contribute to resistance.
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Page 94. The genetic change in the monarch.
569. Karageorgi, M., Groen, S. C., Sumbul, F., Pelaez, J. N., Verster, K. I., Aguilar, J. M., Hastings, A. P., Bernstein, S. L., Matsunaga, T., Astourian, M., Guerra, G., Rico, F., Dobler, S., Agrawal, A. A., & Whiteman, N. K. (2019). Genome editing retraces the evolution of toxin resistance in the monarch butterfly. Nature, 574(7778), 409–412. https://doi.org/10.1038/s41586-019-1610-8
Page 94. Lady Sybi, one of my favorite. Eclampsia is specifically associated with seizure, stroke, or coma during pregnancy owing to high blood pressure and preeclampsia is the lead-up to that condition.
Page 95. Preeclampsia is a major public health problem.
572. Wallis, A. B., Saftlas, A. F., Hsia, J., & Atrash, H. K. (2008). Secular Trends in the Rates of Preeclampsia, Eclampsia, and Gestational Hypertension, United States, 1987-2004. American Journal of Hypertension, 21(5), 521–526. https://doi.org/10.1038/ajh.2008.20
573. Ives, C. W., Sinkey, R., Rajapreyar, I., Tita, A. T. N., & Oparil, S. (2020). Preeclampsia—Pathophysiology and Clinical Presentations. Journal of the American College of Cardiology, 76(14), 1690–1702. https://doi.org/10.1016/j.jacc.2020.08.014
Page 95. Family history.
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Page 95. The specific causes of preeclampsia.
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Page 95. Strangely, a clue to its causes. Quotes in next few paragraphs are from this reference as well.
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Page 95 and 96: The presence of glycoside-like substances. The references also apply to the next paragraph.
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586. Bagrov, A. Y., Fedorova, O. v., Dmitrieva, R. I., Howald, W. N., Hunter, A. P., Kuznetsova, E. A., & Shpen, V. M. (1998). Characterization of a Urinary Bufodienolide Na + ,K + -ATPase Inhibitor in Patients After Acute Myocardial Infarction. Hypertension, 31(5), 1097–1103. https://doi.org/10.1161/01.HYP.31.5.1097 Page 96. In hindsight, we might not.
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Page 96. The use of toad venom. From Act IV, Scene 1, line 1551.
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Page 96. Toad venom is also used in purported.
596. Jeffrey, R. B., Padinjarekuttu, R. R., Theodore, B., Michael, B. H., & Robert, S. H. (1996). Treatment of Toad Venom Poisoning With Digoxin-Specific Fab Fragments. Chest, 110(5), 1282–1288. https://doi.org/10.1378/chest.110.5.1282
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Page 96. Then there is the nine-year-old.
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Page 97. There is a connection here to preeclampsia.
600. Adair, C., Buckalew, V., Graves, S., Lam, G., Johnson, D., Saade, G., Lewis, D., Robinson, C., Danoff, T., Chauhan, N., Hopoate-Sitake, M., Porter, K., Humphrey, R., Trofatter, K., Amon, E., Ward, S., Kennedy, L., Mason, L., & Johnston, J. (2010). Digoxin Immune Fab Treatment for Severe Preeclampsia. American Journal of Perinatology, 27(08), 655–662. https://doi.org/10.1055/s-0030-1249762
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602. Lam, G. K., Hopoate-Sitake, M., Adair, C. D., Buckalew, V. M., Johnson, D. D., Lewis, D. F., Robinson, C. J., Saade, G. R., & Graves, S. W. (2013). Digoxin antibody fragment, antigen binding (Fab), treatment of preeclampsia in women with endogenous digitalis-like factor: a secondary analysis of the DEEP Trial. American Journal of Obstetrics and Gynecology, 209(2), 119.e1-119.e6. https://doi.org/10.1016/j.ajog.2013.04.010
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Page 98. Although nobody knew it at the time.
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Page 99. Such adrenal gland hormones were given. See reference below regarding Ingle’s note that: “Attention focused on a rumor that Germany was buying beef adrenal glands in South America for the purpose of making adrenal cortical extract. It was said that the extract was being used to counteract the hypoxia of Luftwaffe pilots to permit them to fly at higher altitudes.”
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Page 99. In 1940, chemists Russel Marker.
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Page 101. Soybeans have now replaced. Note, however, that the production of other hormone analogs used in contraceptive pill formulations are fully synthetic.
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Page 103. Using flies that grew from. See this quote from page 172 of the reference below: “His life and future scientific activity were immediately influenced by the fly, Calliphora erythrocephala, that he saw come in through an open window and deposit its eggs on a small piece of meat. He watched the larvae emerge from the eggs and grow and–amid all the difficulties of a new language, a new culture, a new family, almost no salary, and using the most primitive tools–conceived the idea that, within a period of two months, resulted in the discovery of the blood-borne factor we now know to be the insect molting hormone, ecdysterone.”
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Page 103. To find out, the World Anti-Doping Agency.
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Page 104. There are some potential downsides.
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Page 106. A close look at the chemical structureof 6-MBOA.
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Page 106. Melatonin is an essential hormone.
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Page 106. Researchers have theorized that 6-MBOA.
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Page 107. How might the connection between 6-MBOA.
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Chapter 6. Abiding Alkaloids
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Page 110. The chemical activates the same capsaicin. This is incorrect. Cinnamaldeyde primarily activates the wasabi receptor TRPA1, not TRPV1.
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Page 110. Capsaicinproduces the heat we feel.
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Page 112. I knew which smell receptors.
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Page 115. Piperidine forms the basis of many alkaloids.
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Page 115. These so-called biogenic.
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Page 115. Humans avoid the smell of death.
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718. Pan, K., Goel, A., Akin, L. R., & Patel, S. R. (2020). Through Plagues and Pandemics: The Evolution of Medical Face Masks. Rhode Island Medical Journal (2013), 103(10), 72–75.
Page 115. Our disdain for these smells.
719. Izquierdo, C., Gómez-Tamayo, J. C., Nebel, J.-C., Pardo, L., & Gonzalez, A. (2018). Identifying human diamine sensors for death related putrescine and cadaverine molecules. PLOS Computational Biology, 14(1), e1005945. https://doi.org/10.1371/journal.pcbi.1005945
Page 115 and 116. Flies have their own.
720. Hussain, A., Zhang, M., Üçpunar, H. K., Svensson, T., Quillery, E., Gompel, N., Ignell, R., & Grunwald Kadow, I. C. (2016). Ionotropic Chemosensory Receptors Mediate the Taste and Smell of Polyamines. PLOS Biology, 14(5), e1002454. https://doi.org/10.1371/journal.pbio.1002454
Page 116. Cadaverine, putrescine, and the related.
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Page 116. Skatole lives up to its name.
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Page 116. In human cells.
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Page 116. One effect of spermidine.
732. Liang, Y., Piao, C., Beuschel, C. B., Toppe, D., Kollipara, L., Bogdanow, B., Maglione, M., Lützkendorf, J., See, J. C. K., Huang, S., Conrad, T. O. F., Kintscher, U., Madeo, F., Liu, F., Sickmann, A., & Sigrist, S. J. (2021). eIF5A hypusination, boosted by dietary spermidine, protects from premature brain aging and mitochondrial dysfunction. Cell Reports, 35(2), 108941. https://doi.org/10.1016/j.celrep.2021.108941
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Page 117. The smell of death.
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Page 117. Over half of all insect species.
737. Schoonhoven, L.M., Van Loon, J.J. and Dicke, M. (2005). Insect-plant biology. Oxford university press.
Page 117. Yet the vast majority of herbivorous insect.
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Page 117. Fraenkel wanted to.
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Page 118. A big hint came from.
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Page 119. May Berenbaum’s studies.
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Page 120. There isn’t always an “orgy of mutual benefaction.” See page 95 in reference below.
751. May, R. M. (1981). Theoretical Ecology: Principles and Applications. Blackwell.
Page 121. Plants, which can be robbed.
752. Irwin, R. E., Bronstein, J. L., Manson, J. S., & Richardson, L. (2010). Nectar Robbing: Ecological and Evolutionary Perspectives. Annual Review of Ecology, Evolution, and Systematics, 41(1), 271–292. https://doi.org/10.1146/annurev.ecolsys.110308.120330
Page 122. It tastes just like Nerds candy. More specifically, the malic acid in Nerds candy is also found typically among the most abundant organic acids in honey bee pollen. There are other organic acids in pollen, which may vary in concentration depending on floral source, such as oxalic acid, tartaric acid, succinic acid, and citric acid
754. Çelik, S., Gerçek, Y. C., Özkök, A., & Ecem Bayram, N. (2022). Organic acids and their derivatives: minor components of bee pollen, bee bread, royal jelly and bee venom. European Food Research and Technology, 248(12), 3037–3057. https://doi.org/10.1007/s00217-022-04110-y
Page 121. Small arums like the.
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Page 121. In Sumatra, the titan arum.
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Page 122. Bouquets of anise, banana, booze.
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Page 122. Neuroethologist Marcus Stensmyr.
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Page 123. Children can also be.
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Page 123. If enough tissue is ingested.
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Page 123. Although not an alkaloid, oxalate.
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Page 124. This pattern repeats itself.
763. Cipollini, M. L., & Levey, D. J. (1997). Secondary Metabolites Of Fleshy Vertebrate‐Dispersed Fruits: Adaptive Hypotheses And Implications For Seed Dispersal. The American Naturalist, 150(3), 346–372. https://doi.org/10.1086/286069
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764. Nakamura, Y., Yoshimoto, M., Murata, Y., Shimoishi, Y., Asai, Y., Park, E. Y., Sato, K., & Nakamura, Y. (2007). Papaya Seed Represents a Rich Source of Biologically Active Isothiocyanate. Journal of Agricultural and Food Chemistry, 55(11), 4407–4413. https://doi.org/10.1021/jf070159w
767. Nathan, R., Schurr, F. M., Spiegel, O., Steinitz, O., Trakhtenbrot, A., & Tsoar, A. (2008). Mechanisms of long-distance seed dispersal. Trends in Ecology & Evolution, 23(11), 638–647. https://doi.org/10.1016/j.tree.2008.08.003
768. Herrera, C. M. (1985). Determinants of Plant-Animal Coevolution: The Case of Mutualistic Dispersal of Seeds by Vertebrates. Oikos, 44(1), 132. https://doi.org/10.2307/3544054
769. Platt, S. G., Elsey, R. M., Liu, H., Rainwater, T. R., Nifong, J. C., Rosenblatt, A. E., Heithaus, M. R., & Mazzotti, F. J. (2013). Frugivory and seed dispersal by crocodilians: an overlooked form of saurochory? Journal of Zoology, 291(2), 87–99. https://doi.org/10.1111/jzo.12052
770. Gottsberger, G. (1978). Seed Dispersal by Fish in the Inundated Regions of Humaita, Amazonia. Biotropica, 10(3), 170. https://doi.org/10.2307/2387903
771. Anderson, J. T., Nuttle, T., Saldaña Rojas, J. S., Pendergast, T. H., & Flecker, A. S. (2011). Extremely long-distance seed dispersal by an overfished Amazonian frugivore. Proceedings of the Royal Society B: Biological Sciences, 278(1723), 3329–3335. https://doi.org/10.1098/rspb.2011.0155
Page 125. As a UMSL graduate student. Work on toucans in South America is highlighted below in addition to her previous work on hornbills in Africa.
772. Holbrook, K. M., & Loiselle, B. A. (2009). Dispersal in a Neotropical tree, Virola flexuosa (Myristicaceae): Does hunting of large vertebrates limit seed removal? Ecology, 90(6), 1449–1455. https://doi.org/10.1890/08-1332.1
773. Karubian, J., Browne, L., Bosque, C., Carlo, T., Galetti, M., Loiselle, B. A., ... & Wikelski, M. (2012). Seed dispersal by neotropical birds: emerging patterns and underlying processes. Ornitologia Neotropical, 23, 9-14.
775. Holbrook, K. M., Smith, T. B., & Hardesty, B. D. (2002). Implications of long-distance movements of frugivorous rain forest hornbills. Ecography, 25(6), 745–749. https://doi.org/10.1034/j.1600-0587.2002.250610.x
Page 125. From the seed’s perspective.
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Page 125. Some nutmeg seeds.
778. Huang, Y., Tan, J. M. W. L., Kini, R. M., & Ho, S. H. (1997). Toxic and antifeedant action of nutmeg oil against Tribolium castaneum (Herbst) and Sitophilus zeamais Motsch. Journal of Stored Products Research, 33(4), 289–298. https://doi.org/10.1016/S0022-474X(97)00009-X
Page 125. In the human body.
779. Shulgin, A. T. (1966). Possible Implication of Myristicin as a Psychotropic Substance. Nature, 210(5034), 380–384. https://doi.org/10.1038/210380a0
780. Shulgin, A. T., Sargent, T., & Naranjo, C. (1973). Animal Pharmacology and Human Psychopharmacology of 3-Methoxy-4,5-Methylenedioxyphenylisopropylamine (MMDA). Pharmacology, 10(1), 12–18. https://doi.org/10.1159/000136416
781. Yang, K. H., Han, B. H., & Palamar, J. J. (2022). Past-year hallucinogen use in relation to psychological distress, depression, and suicidality among US adults. Addictive Behaviors, 132, 107343. https://doi.org/10.1016/j.addbeh.2022.107343
784. Sihotang, V. B. L., Yang, G., Chi, X., & Huang, L. (2018). The ethnobotanical survey of clove, pepper, and nutmeg and their utilization by Chinese and Indonesian people. Journal of Tropical Biology & Conservation (JTBC), 15, 15â-27.
Page 126. Amphetamines generally work.
785. Robertson, S. D., Matthies, H. J. G., & Galli, A. (2009). A Closer Look at Amphetamine-Induced Reverse Transport and Trafficking of the Dopamine and Norepinephrine Transporters. Molecular Neurobiology, 39(2), 73–80. https://doi.org/10.1007/s12035-009-8053-4
786. Sulzer, D., Sonders, M. S., Poulsen, N. W., & Galli, A. (2005). Mechanisms of neurotransmitter release by amphetamines: A review. Progress in Neurobiology, 75(6), 406–433. https://doi.org/10.1016/j.pneurobio.2005.04.003
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Page 126. Amphetamines are also made.
788. Zheng, Q., Mu, X., Pan, S., Luan, R., & Zhao, P. (2023). Ephedrae herba: A comprehensive review of its traditional uses, phytochemistry, pharmacology, and toxicology. Journal of Ethnopharmacology, 307, 116153. https://doi.org/10.1016/j.jep.2023.116153
789. Hattori, Y., Ishii, K., Yanai, K., & Endoh, M. (2023). The large part German medicine has played in the development of experimental pharmacology in Japan. Naunyn-Schmiedeberg’s Archives of Pharmacology, 396(1), 35–42. https://doi.org/10.1007/s00210-022-02308-1
790. Morelli, M., & Tognotti, E. (2021). Brief history of the medical and non-medical use of amphetamine-like psychostimulants. Experimental Neurology, 342, 113754. https://doi.org/10.1016/j.expneurol.2021.113754
792. CMEA (Combat Methamphetamine Epidemic Act of 2005). (2005). U. S. Department of Justice, Drug Enforcement Administration, Diversion Control Division. https://www.deadiversion.usdoj.gov/meth/index.html
795. Substance Abuse and Mental Health Services Administration. (2021). Key substance use and mental health indicators in the United States: Results from the 2020 National Survey on Drug Use and Health (HHS Publication No. PEP21-07-01-003, NSDUH Series H-56). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. Retrieved from https://www.samhsa.gov/data/. See: https://www.samhsa.gov/data/report/2020-nsduh-annual-national-report
Page 127. The combination of meth.
796. Centers for Disease Control and Prevention. (2020). Increase in Fatal Drug Overdoses Across the United States Driven by Synthetic Opioids Before and During the COVID-19 Pandemic. Health Alert Network. https://emergency.cdc.gov/han/2020/han00438.asp
Page 127. Like ma huang, a plant called khat.
797. Giannini, A. J., Burge, H., Shaheen, J. M., & Price, W. A. (1986). Khat: Another Drug of Abuse? Journal of Psychoactive Drugs, 18(2), 155–158. https://doi.org/10.1080/02791072.1986.10471395
798. Balint, E. E., Falkay, G., & Balint, G. A. (2009). Khat – a controversial plant. Wiener Klinische Wochenschrift, 121(19–20), 604–614. https://doi.org/10.1007/s00508-009-1259-7
799. Al-Mugahed, L. (2008). Khat chewing in Yemen: turning over a new leaf. Bulletin of the World Health Organization, 86(10), 741–742. https://doi.org/10.2471/BLT.08.011008
800. Haile, D., & Lakew, Y. (2015). Khat Chewing Practice and Associated Factors among Adults in Ethiopia: Further Analysis Using the 2011 Demographic and Health Survey. PLOS ONE, 10(6), e0130460. https://doi.org/10.1371/journal.pone.0130460
Page 127. Cathinones work on the brain.
801. Baumann, M. H., Walters, H. M., Niello, M., & Sitte, H. H. (2018). Neuropharmacology of Synthetic Cathinones. In H. H. Maurer & S. D. Brandt (Eds.), New Psychoactive Substances : Pharmacology, Clinical, Forensic and Analytical Toxicology (pp. 113–142). Springer International Publishing. https://doi.org/10.1007/164_2018_178
Page 127. Another set of alkaloids, on the other hand.
803. Sheldrake, M. (2020). The ‘enigma’ of Richard Schultes, Amazonian hallucinogenic plants, and the limits of ethnobotany. Social Studies of Science, 50(3), 345–376. https://doi.org/10.1177/0306312720920362
804. Schultes, R. E.; Hofmann A. (1979). Plants of the Gods: Origins of Hallucinogenic Use. New York: McGraw-Hill. ISBN 0-07-056089-7.
805. Schultes R. E. (1970). The New World Indians and their hallucinogenic plants.
806. Davis W. (1996). One River: Explorations and Discoveries in the Amazon Rain Forest. Simon and Schuster, Inc.
Page 128. One such alkaloid.
807. Agurell, S., Holmstedt, B., Lindgren, J.-E., Schultes, R. E., Lindberg, A. A., Jansen, G., Lamm, B., & Samuelsson, B. (1969). Alkaloids in Certain Species of Virola and Other South American Plants of Ethnopharmacologic Interest. Acta Chemica Scandinavica, 23, 903–916. https://doi.org/10.3891/acta.chem.scand.23-0903
808. Schultes, R. E. (1969). Virola as an orally administered hallucinogen. Botanical Museum Leaflets, Harvard University, 22(6), 229–240. http://www.jstor.org/stable/41753106
810. Manske, R. H. F. (1931). A SYNTHESIS OF THE METHYLTRYPTAMINES AND SOME DERIVATIVES. Canadian Journal of Research, 5(5), 592–600. https://doi.org/10.1139/cjr31-097
813. McKenna, D., & Riba, J. (2018). New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca. In A. L. Halberstadt, F. X. Vollenweider, & D. E. Nichols (Eds.), Behavioral Neurobiology of Psychedelic Drugs (pp. 283–311). Springer Berlin Heidelberg. https://doi.org/10.1007/7854_2016_472
815. Chilton, W. S., Bigwood, J., & Jensen, R. E. (1979). Psilocin, Bufotenine and Serotonin: Historical and Biosynthetic Observations. Journal of Psychedelic Drugs, 11(1–2), 61–69. https://doi.org/10.1080/02791072.1979.10472093
816. Sherwood, A. M., Claveau, R., Lancelotta, R., Kaylo, K. W., & Lenoch, K. (2020). Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use. ACS Omega, 5(49), 32067–32075. https://doi.org/10.1021/acsomega.0c05099
818. Pachter , I. J., Zacharias, D. E., & Ribeiro , O. (1959). Indole Alkaloids of Acer saccharinum (the Silver Maple), Dictyoloma incanescens, Piptadenia colubrina, and Mimosa hostilis. The Journal of Organic Chemistry, 24(9), 1285–1287. https://doi.org/10.1021/jo01091a032
819. Torres CM, Repke DB (2006). Anadenanthera: visionary plant of ancient South America. Routledge, London.
Page 128. Magic mushrooms contain the tryptamine.
820. Reynolds, H. T., Vijayakumar, V., Gluck-Thaler, E., Korotkin, H. B., Matheny, P. B., & Slot, J. C. (2018). Horizontal gene cluster transfer increased hallucinogenic mushroom diversity. Evolution Letters, 2(2), 88–101. https://doi.org/10.1002/evl3.42
821. Guzman, G. (2005). Species Diversity of the Genus Psilocybe (Basidiomycotina, Agaricales, Strophariaceae) in the World Mycobiota, with Special Attention to Hallucinogenic Properties. International Journal of Medicinal Mushrooms, 7(1–2), 305–332. https://doi.org/10.1615/IntJMedMushr.v7.i12.280
822. Beug, M. W., & Bigwood, J. (1982). Psilocybin and psilocin levels in twenty species from seven genera of wild mushrooms in the Pacific Northwest, U.S.A. Journal of Ethnopharmacology, 5(3), 271–285. https://doi.org/10.1016/0378-8741(82)90013-7
823. Hofmann, A., Heim, R., Brack, A., & Kobel, H. (1958). [Psilocybin, a psychotropic substance from the Mexican mushroom Psilicybe mexicana Heim]. Experientia, 14(3), 107–109. https://doi.org/10.1007/BF02159243
824. Hofmann, A., Frey, A., Ott, H., Petrzilka, Th., & Troxler, F. (1958). Konstitutionsaufklärung und Synthese von Psilocybin. Experientia, 14(11), 397–399. https://doi.org/10.1007/BF02160424
827. Weil, A. T., & Davis, W. (1994). Bufo alvarius: a potent hallucinogen of animal origin. Journal of Ethnopharmacology, 41(1–2), 1–8. https://doi.org/10.1016/0378-8741(94)90051-5
829. See this quote “However, the purpose of these ancient practices has not been fully clarified, and evidence of use as a medicine is scarce. Therefore, it cannot be ruled out that the present use of toad secretion is of more recent origin.” from Uthaug, M. v., Lancelotta, R., van Oorsouw, K., Kuypers, K. P. C., Mason, N., Rak, J., Šuláková, A., Jurok, R., Maryška, M., Kuchař, M., Páleníček, T., Riba, J., & Ramaekers, J. G. (2019). A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms. Psychopharmacology, 236(9), 2653–2666. https://doi.org/10.1007/s00213-019-05236-w
830. See this quote: “Still, some of the most influential figures in the Bufo scene have promoted Indigenous connections. Dr. Octavio Rettig, a physician from Guadalajara, Mexico, said he introduced the substance to the Seri people in northwestern Mexico in 2011 in a bid to combat crystal meth addiction. “After they got the medicine, they started to put the puzzle together,” said Dr. Rettig, 43, citing what he believes was a rescue of the Seri’s “lost traditions.” “They recognized the benefits of the toad medicine.” From: Romero, S. (2023, June 22). Demand for This Toad’s Psychedelic Toxin Is Booming. Some Warn That’s Bad for the Toad. New York Times. https://www.nytimes.com/2022/03/20/us/toad-venom-psychedelic.html
831. Davis, A. K., So, S., Lancelotta, R., Barsuglia, J. P., & Griffiths, R. R. (2019). 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) used in a naturalistic group setting is associated with unintended improvements in depression and anxiety. Am. J. Drug Alcohol Abuse, 45(2), 161–169. https://doi.org/10.1080/00952990.2018.1545024
Page 128. In fact, the practice of smoking toad venom.
833. de Rios, M. D., Alger, N., Crumrine, N. R., Furst, P. T., Harman, R. C., Hellmuth, N. M., Hopkins, N. A., King, W. C., Koss, J. D., La Barre, W., Landar, H. J., Long, J. K., Proskouriakoff, T., Rubel, A. J., Samaranch, F., J. Eric S. Thompson, & Wescott, R. W. (1974). The Influence of Psychotropic Flora and Fauna on Maya Religion [and Comments and Reply]. Current Anthropology, 15(2), 147–164. http://www.jstor.org/stable/2740991
834. Kennedy, A. B. (1982). Ecce Bufo: The Toad in Nature and in Olmec Iconography. Current Anthropology, 23(3), 273–290. https://doi.org/10.1086/202831
Page 129. DMTs bind to our.
835. Aghajanian, G. K., Foote, W. E., & Sheard, M. H. (1968). Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe. Science, 161(3842), 706–708. https://doi.org/10.1126/science.161.3842.706
836. Glennon, R. A., Titeler, M., & Young, R. (1986). Structure-activity relationships and mechanism of action of hallucinogenic agents based on drug discrimination and radioligand binding studies. Psychopharmacology Bulletin, 22(3), 953–958.
837. Glennon, R. A., & Gessner, P. K. (1979). Serotonin receptor binding affinities of tryptamine analogs. Journal of Medicinal Chemistry, 22(4), 428–432. https://doi.org/10.1021/jm00190a014
838. González-Maeso, J., Weisstaub, N. v., Zhou, M., Chan, P., Ivic, L., Ang, R., Lira, A., Bradley-Moore, M., Ge, Y., Zhou, Q., Sealfon, S. C., & Gingrich, J. A. (2007). Hallucinogens Recruit Specific Cortical 5-HT2A Receptor-Mediated Signaling Pathways to Affect Behavior. Neuron, 53(3), 439–452. https://doi.org/10.1016/j.neuron.2007.01.008
839. López-Giménez, J. F., & González-Maeso, J. (2018). Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways. Current Topics in Behavioral Neurosciences, 36, 45–73. https://doi.org/10.1007/7854_2017_478
840. Vollenweider, F. X., Vollenweider-Scherpenhuyzen, M. F. I., Bäbler, A., Vogel, H., & Hell, D. (1998). Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. NeuroReport, 9(17), 3897–3902. https://doi.org/10.1097/00001756-199812010-00024
Page 129. The velvet bean.
841. Pulikkalpura, H., Kurup, R., Mathew, P. J., & Baby, S. (2015). Levodopa in Mucuna pruriens and its degradation. Scientific reports, 5, 11078. https://doi.org/10.1038/srep11078
843. Torres, C. M., & Repke, D. B. (2014). Anadenanthera: visionary plant of ancient South America. Routledge.
844. Altschul, S. R. (1972). The genus Anadenanthera in Amerindian cultures. Mass., Harvard University.
845. Knobloch, P. J. (2000). Wari Ritual Power at Conchopata: An Interpretation of Anadenanthera Colubrina Iconography. Latin American Antiquity, 11(4), 387–402. https://doi.org/10.2307/972003
846. Bélisle, V. (2019). Hallucinogens and Altered States of Consciousness in Cusco, Peru: A Path to Local Power during Wari State Expansion. Cambridge Archaeological Journal,29(3), 375-391. doi:10.1017/S0959774319000015
Page 129 and 130. Butotenine, probably derived from Anadenanthera.
847. Miller, M. J., Albarracin-Jordan, J., Moore, C., & Capriles, J. M. (2019). Chemical evidence for the use of multiple psychotropic plants in a 1,000-year-old ritual bundle from South America. Proceedings of the National Academy of Sciences of the United States of America, 116(23), 11207–11212. https://doi.org/10.1073/pnas.1902174116
Page 130 and 131. DMT is also the principal. These references apply to the next three paragraphs.
848. Holmstedt, B., & Lindgren, J. (1967). Chemical constituents and pharmacology of South American snuffs. Psychopharmacology Bulletin, 4(3), 16.
849. Spruce, R (1908). Notes of a Botanist on the Amazon and Andes (two volumes). Macmillian, London. Reprinted by Johnson Reprint, New York, 1970.
850. Rivier, L., & Lindgren, J.-E. (1972). “Ayahuasca,” the South American hallucinogenic drink: An ethnobotanical and chemical investigation. Economic Botany, 26(2), 101–129. https://doi.org/10.1007/BF02860772
851. Schultes, R. E. (1980). The botany and chemistry of hallucinogens. Thomas.
852. Schultes, R. E. (1957). The identity of the malpighiaceous narcotics of South America. Botanical Museum Leaflets, Harvard University, 18(1), 1-56. http://www.jstor.org/stable/41762183
853. Pinkley, H. v. (1969). Plant admixtures to Ayahuasca, the South American hallucinogenic drink. Lloydia, 32(3), 305–314.
854. McKenna, D. J., Towers, G. H. N., & Abbott, F. (1984). Monoamine oxidase inhibitors in South American hallucinogenic plants: Tryptamine and β-carboline constituents of Ayahuasca. Journal of Ethnopharmacology, 10(2), 195–223. https://doi.org/10.1016/0378-8741(84)90003-5
855. Callaway, J. C., McKenna, D. J., Grob, C. S., Brito, G. S., Raymon, L. P., Poland, R. E., Andrade, E. N., Andrade, E. O., & Mash, D. C. (1999). Pharmacokinetics of Hoasca alkaloids in healthy humans. Journal of Ethnopharmacology, 65(3), 243–256. https://doi.org/10.1016/S0378-8741(98)00168-8
856. McKenna, D., & Riba, J. (2018). New World Tryptamine Hallucinogens and the Neuroscience of Ayahuasca. In A. L. Halberstadt, F. X. Vollenweider, & D. E. Nichols (Eds.), Behavioral Neurobiology of Psychedelic Drugs (pp. 283–311). Springer Berlin Heidelberg. https://doi.org/10.1007/7854_2016_472
857. Callaway, J. C. (2005). Various Alkaloid Profiles in Decoctions of Banisteriopsis Caapi. Journal of Psychoactive Drugs, 37(2), 151–155. https://doi.org/10.1080/02791072.2005.10399796
Page 131. In contrast, when toad venom is smoked.
858. Davis, A. K., Barsuglia, J. P., Lancelotta, R., Grant, R. M., & Renn, E. (2018). The epidemiology of 5-methoxy- N, N -dimethyltryptamine (5-MeO-DMT) use: Benefits, consequences, patterns of use, subjective effects, and reasons for consumption. Journal of Psychopharmacology, 32(7), 779–792. https://doi.org/10.1177/0269881118769063
859. Barsuglia, J., Davis, A. K., Palmer, R., Lancelotta, R., Windham-Herman, A.-M., Peterson, K., Polanco, M., Grant, R., & Griffiths, R. R. (2018). Intensity of Mystical Experiences Occasioned by 5-MeO-DMT and Comparison With a Prior Psilocybin Study. Frontiers in Psychology, 9. https://doi.org/10.3389/fpsyg.2018.02459
860. Uthaug, M. V., Lancelotta, R., Ortiz Bernal, A. M., Davis, A. K., & Ramaekers, J. G. (2020). A comparison of reactivation experiences following vaporization and intramuscular injection (IM) of synthetic 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting. Journal of Psychedelic Studies, 4(2), 104–113. https://doi.org/10.1556/2054.2020.00123
861. Brush, D. E., Bird, S. B., & Boyer, E. W. (2004). Monoamine Oxidase Inhibitor Poisoning Resulting from Internet Misinformation on Illicit Substances. Journal of Toxicology: Clinical Toxicology, 42(2), 191–195. https://doi.org/10.1081/CLT-120030949
Page 131. Psilocin is ultimately detoxified.
862. Lenz, C., Dörner, S., Trottmann, F., Hertweck, C., Sherwood, A., & Hoffmeister, D. (2022). Assessment of Bioactivity‐Modulating Pseudo‐Ring Formation in Psilocin and Related Tryptamines. ChemBioChem, 23(13). https://doi.org/10.1002/cbic.202200183
863. Blei, F., Dörner, S., Fricke, J., Baldeweg, F., Trottmann, F., Komor, A., Meyer, F., Hertweck, C., & Hoffmeister, D. (2020). Simultaneous Production of Psilocybin and a Cocktail of β‐Carboline Monoamine Oxidase Inhibitors in “Magic” Mushrooms. Chemistry – A European Journal, 26(3), 729–734. https://doi.org/10.1002/chem.201904363
864. Lenz, C., Sherwood, A., Kargbo, R., & Hoffmeister, D. (2021). Taking Different Roads: <scp>l</scp> ‐Tryptophan as the Origin of Psilocybe Natural Products. ChemPlusChem, 86(1), 28–35. https://doi.org/10.1002/cplu.202000581
Page 131. Nowhere were Psilocybe and the many.
865. Schultes, R. E. (1940). Teonanacatl: The Narcotic Mushroom of the Aztecs. American Anthropologist, 42(3), 429–443. http://www.jstor.org/stable/663232
867. Singer, R. (1958). Mycological Investigations on Teonanacatl, the Mexican Hallucinogenic Mushroom. Part I. The History of Teonanacatl, Field Work and Culture Work. Mycologia, 50(2), 239. https://doi.org/10.2307/3756196
868. Singer, R., & Smith, A. H. (1958). Mycological Investigations on Teonanacatl, the Mexican Hallucinogenic Mushroom. Part II. A Taxonomic Monograph of Psilocybe, Section Caerulescentes. Mycologia, 50(2), 262. https://doi.org/10.2307/3756197
869. Weber, H. P., & Petcher, T. J. (1974). Crystal structures of the Teonanácatl hallucinogens. Part I. Psilocybin C 12 H 17 N 2 O 4 P. J. Chem. Soc., Perkin Trans. 2, 8, 942–946. https://doi.org/10.1039/P29740000942
870. Petcher, T. J., & Weber, H. P. (1974). Crystal structures of the Teonanácatl hallucinogens. Part II. Psilocin, C 12 H 15 N 2 O. J. Chem. Soc., Perkin Trans. 2, 8, 946–948. https://doi.org/10.1039/P29740000946
Page 131. Two other important serotonin. The next two paragraphs rely on the references below.
871. de Groot, A. N. J. A., van Dongen, P. W. J., Vree, T. B., Hekster, Y. A., & van Roosmalen, J. (1998). Ergot Alkaloids. Drugs, 56(4), 523–535. https://doi.org/10.2165/00003495-199856040-00002
872. Lee, M. R. (2009). The history of ergot of rye (Claviceps purpurea) I: from antiquity to 1900. The Journal of the Royal College of Physicians of Edinburgh, 39(2), 179-184.
873. Hofmann, A., & Ott, J. (1983). LSD, my problem child: Reflections on sacred drugs, mysticism, and science (p. 224). Los Angeles, CA: JP Tarcher.
Page 132. Mescaline is found only.
874. Jay, M. (2019). Mescaline: a global history of the first psychedelic. Yale University Press.
875. Gurschler, I. (2019). The fourfold discovery of Mescaline (1896–1919). Monatshefte Für Chemie - Chemical Monthly, 150(5), 941–947. https://doi.org/10.1007/s00706-019-02444-0
876. Dobkin, M. (1968). Trichocereus pachanoi—A mescaline cactus used in folk healing in Peru. Economic Botany, 22(2), 191–194. https://doi.org/10.1007/BF02860562
877. Ma, W. W., Jiang, X. Y., Cooks, R. G., McLaughlin, J. L., Gibson, A. C., Zeylemaker, F., & Ostolaza, C. N. (1986). Cactus Alkaloids, LXI. Identification of Mescaline and Related Compounds in Eight Additional Species Using Tlc and Ms/ms. Journal of Natural Products, 49(4), 735–737. https://doi.org/10.1021/np50046a050
878. Watkins, J. L., Li, Q., Yeaman, S., & Facchini, P. J. (2023). Elucidation of the mescaline biosynthetic pathway in peyote ( Lophophora williamsii ). The Plant Journal. https://doi.org/10.1111/tpj.16447
879. Carod-Artal, F. J., & Vázquez-Cabrera, C. B. (2006). [Mescaline and the San Pedro cactus ritual: archaeological and ethnographic evidence in northern Peru]. Revista de Neurologia, 42(8), 489–498.
880. Ogunbodede, O., McCombs, D., Trout, K., Daley, P., & Terry, M. (2010). New mescaline concentrations from 14 taxa/cultivars of Echinopsis spp. (Cactaceae) (“San Pedro”) and their relevance to shamanic practice. Journal of Ethnopharmacology, 131(2), 356–362. https://doi.org/10.1016/j.jep.2010.07.021
881. Davis, E. W. (1983). SACRED PLANTS OF THE SAN PEDRO CULT. Botanical Museum Leaflets, Harvard University, 29(4), 367–386. http://www.jstor.org/stable/41762855
882. El-Seedi, H. R., Smet, P. A. G. M. de, Beck, O., Possnert, G., & Bruhn, J. G. (2005). Prehistoric peyote use: Alkaloid analysis and radiocarbon dating of archaeological specimens of Lophophora from Texas. Journal of Ethnopharmacology, 101(1–3), 238–242. https://doi.org/10.1016/j.jep.2005.04.022
Page 133. Why psychedelic alkaloids. Tangential evidence of anti-herbivore or anti-pathogen from related alkaloids is below (although not all are psychedelic).
884. Thomas, J. C., Saleh, E. F., Alammar, N., & Akroush, A. M. (1998). The Indole Alkaloid Tryptamine Impairs Reproduction in Drosophila melanogaster. Journal of Economic Entomology, 91(4), 841–846. https://doi.org/10.1093/jee/91.4.841
885. Miles, D. H., Ly, A. M., Randle, S. A., Hedin, P. A., & Burks, M. L. (1987). Alkaloidal insect antifeedants from Virola calophylla Warb. Journal of Agricultural and Food Chemistry, 35(5), 794–797. https://doi.org/10.1021/jf00077a037
Page 133. Among the plants.
886. Simpson, B. H., Jolly, R. D., & Thomas, S. H. M. (1969). Phalaris arundinacea as a cause of deaths and incoordination in sheep. New Zealand Veterinary Journal, 17(12), 240–244. https://doi.org/10.1080/00480169.1969.33837
887. Ulvund, M. J. (1985). Chronic Poisoning in a Lamb Grazing Phalaris arundinacea. Acta Veterinaria Scandinavica, 26(2), 286–288. https://doi.org/10.1186/BF03546558
888. Marten, G. C., Jordan, R. M., & Hovin, A. W. (1976). Biological Significance of Reed Canarygrass Alkaloids and Associated Palatability Variation to Grazing Sheep and Cattle. Agronomy Journal, 68(6), 909–914. https://doi.org/10.2134/agronj1976.00021962006800060017x
889. Culvenor, C., Dal Bon, R., & Smith, L. (1964). The occurrence of indolealkylamine alkaloids in Phalaris tuberosa L. and P. arundinacea L. Australian Journal of Chemistry, 17(11), 1301. https://doi.org/10.1071/CH9641301
891. Read, E., Reddy, P., Rendell, D., & Rochfort, S. (2020). Changes in field concentrations of five phalaris alkaloids and their association with toxicity in pastures of Victoria, Australia. Crop and Pasture Science, 71(4), 389. https://doi.org/10.1071/CP19293
892. Alden, R., Hackney, B., Weston, L. A., & Quinn, J. C. (2014). Phalaris Toxicoses in Australian Livestock Production Systems: Prevalence, Aetiology and Toxicology. Journal of Toxins, 1(1). https://doi.org/10.13188/2328-1723.1000003
893. Rendig, V., Cooper, D., Dunbar, J., Lawrence, C., Clawson, W., Bushnell, R., & McComb, E. (1976). Phalaris “staggers” in California. California agriculture, 30(6), 8-10.
894. Wilkinson, S. (1958). 428. 5-Methoxy-N-methyltryptamine: a new indole alkaloid from Phalaris arundinacea L. Journal of the Chemical Society (Resumed), 2079. https://doi.org/10.1039/jr9580002079
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896. Gallagher, C. H., Koch, J. H., & Hoffman, H. (1967). Electro-myographic studies on sheep injected with the n,n-dimethylated tryptamine alkaloids ofphalaris tuberosa. International Journal of Neuropharmacology, 6(3), 223-IN10. https://doi.org/10.1016/0028-3908(67)90009-3
897. Brito-da-Costa, A. M., Dias-da-Silva, D., Gomes, N. G. M., Dinis-Oliveira, R. J., & Madureira-Carvalho, Á. (2020). Toxicokinetics and Toxicodynamics of Ayahuasca Alkaloids N,N-Dimethyltryptamine (DMT), Harmine, Harmaline and Tetrahydroharmine: Clinical and Forensic Impact. Pharmaceuticals, 13(11), 334. https://doi.org/10.3390/ph13110334
Page 133. For magic mushrooms and psilocybin.
898. Levine, W. G. (1967). Formation of blue oxidation product from psilocybin. Nature, 215(5107), 1292–1293. https://doi.org/10.1038/2151292a0
899. Lenz, C., Wick, J., Braga, D., García‐Altares, M., Lackner, G., Hertweck, C., Gressler, M., & Hoffmeister, D. (2020). Injury‐Triggered Blueing Reactions of Psilocybe “Magic” Mushrooms. Angewandte Chemie International Edition, 59(4), 1450–1454. https://doi.org/10.1002/anie.201910175
900. Leopoldini, M., Marino, T., Russo, N., & Toscano, M. (2004). Antioxidant Properties of Phenolic Compounds: H-Atom versus Electron Transfer Mechanism. The Journal of Physical Chemistry A, 108(22), 4916–4922. https://doi.org/10.1021/jp037247d
902. Reynolds, H. T., Vijayakumar, V., Gluck-Thaler, E., Korotkin, H. B., Matheny, P. B., & Slot, J. C. (2018). Horizontal gene cluster transfer increased hallucinogenic mushroom diversity. Evolution Letters, 2(2), 88–101. https://doi.org/10.1002/evl3.42
903. Meyer, M., & Slot, J. (2023). The evolution and ecology of psilocybin in nature. Fungal Genetics and Biology, 167, 103812. https://doi.org/10.1016/j.fgb.2023.103812
904. Spiteller, P. (2008). Chemical Defence Strategies of Higher Fungi. Chemistry - A European Journal, 14(30), 9100–9110. https://doi.org/10.1002/chem.200800292
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906. Boyce, G. R., Gluck-Thaler, E., Slot, J. C., Stajich, J. E., Davis, W. J., James, T. Y., Cooley, J. R., Panaccione, D. G., Eilenberg, J., de Fine Licht, H. H., Macias, A. M., Berger, M. C., Wickert, K. L., Stauder, C. M., Spahr, E. J., Maust, M. D., Metheny, A. M., Simon, C., Kritsky, G., … Kasson, M. T. (2019). Psychoactive plant- and mushroom-associated alkaloids from two behavior modifying cicada pathogens. Fungal Ecology, 41, 147–164. https://doi.org/10.1016/j.funeco.2019.06.002
907. Lovett, B., Macias, A., Stajich, J. E., Cooley, J., Eilenberg, J., de Fine Licht, H. H., & Kasson, M. T. (2020). Behavioral betrayal: How select fungal parasites enlist living insects to do their bidding. PLOS Pathogens, 16(6), e1008598. https://doi.org/10.1371/journal.ppat.1008598
909. Wäli, P. P., Wäli, P. R., Saikkonen, K., & Tuomi, J. (2013). Is the Pathogenic Ergot Fungus a Conditional Defensive Mutualist for Its Host Grass? PLoS ONE, 8(7), e69249. https://doi.org/10.1371/journal.pone.0069249
Page 134. A similar question exists for mescaline.
910. Lin, J., Yang, S., Ji, J., Xiang, P., Wu, L., & Chen, H. (2023). Natural or artificial: An example of topographic spatial distribution analysis of mescaline in cactus plants by matrix-assisted laser desorption/ionization mass spectrometry imaging. Frontiers in Plant Science, 14. https://doi.org/10.3389/fpls.2023.1066595
911. Newbold, R., de Silva, S., & Terry, M. (2020). Correlation of mescaline concentrations in Lophophora williamsii (Cactaceae) with rib numbers and diameter of crown (U.S.A.). Journal of the Botanical Research Institute of Texas, 14(1), 103–120. https://doi.org/10.17348/jbrit.v14.i1.901
912. Levin, D. A., & York, B. M. (1978). The toxicity of plant alkaloids: an Ecogeographic perspective. Biochemical Systematics and Ecology, 6(1), 61–76. https://doi.org/10.1016/0305-1978(78)90026-1
913. Sogawa, K. (1971). Preliminary assay of antifeeding chemicals for the brown planthopper, Nilaparvata lugens (Stal)(Hemiptera: Delphacidae). Applied entomology and zoology, 6(4), 215-218.
914. Corio, C., Soto, I. M., Carreira, V., Padró, J., Betti, M. I. L., & Hasson, E. (2013). An alkaloid fraction extracted from the cactus Trichocereus terscheckii affects fitness in the cactophilic fly Drosophila buzzatii (Diptera: Drosophilidae). Biological Journal of the Linnean Society, 109(2), 342–353. https://doi.org/10.1111/bij.12036
915. Padró, J., Carreira, V., Corio, C., Hasson, E., & Soto, I. M. (2014). Host alkaloids differentially affect developmental stability and wing vein canalization in cactophilic Drosophila buzzatii. Journal of Evolutionary Biology, 27(12), 2781–2797. https://doi.org/10.1111/jeb.12537
916. Soto, I. M., Carreira, V. P., Corio, C., Padró, J., Soto, E. M., & Hasson, E. (2014). Differences in Tolerance to Host Cactus Alkaloids in Drosophila koepferae and D. buzzatii. PLoS ONE, 9(2), e88370. https://doi.org/10.1371/journal.pone.0088370
Page 134. The visual hallucinations.
917. Siegel, R. K., & Jarvik, M. E. (1980). DMT self-administration by monkeys in isolation. Bulletin of the Psychonomic Society, 16(2), 117–120. https://doi.org/10.3758/BF03334456
919. Franzen, FR., & Gross, H. (1965). Tryptamine, N,N-Dimethyltryptamine, N,N-Dimethyl-5-hydroxytryptamine and 5-Methoxytryptamine in Human Blood and Urine. Nature, 206(4988), 1052–1052. https://doi.org/10.1038/2061052a0
920. Barker, S. A., McIlhenny, E. H., & Strassman, R. (2012). A critical review of reports of endogenous psychedelic N, N‐dimethyltryptamines in humans: 1955–2010. Drug Testing and Analysis, 4(7–8), 617–635. https://doi.org/10.1002/dta.422
921. Kärkkäinen, J., Forsström, T., Tornaeus, J., Wähälä, K., Kiuru, P., Honkanen, A., Stenman, U. ‐H., Turpeinen, U., & Hesso, A. (2005). Potentially hallucinogenic 5‐hydroxytryptamine receptor ligands bufotenine and dimethyltryptamine in blood and tissues. Scandinavian Journal of Clinical and Laboratory Investigation, 65(3), 189–199. https://doi.org/10.1080/00365510510013604
922. Dean, J. G., Liu, T., Huff, S., Sheler, B., Barker, S. A., Strassman, R. J., Wang, M. M., & Borjigin, J. (2019). Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain. Scientific Reports, 9(1), 9333. https://doi.org/10.1038/s41598-019-45812-w
923. Dean, J. G., Liu, T., Huff, S., Sheler, B., Barker, S. A., Strassman, R. J., Wang, M. M., & Borjigin, J. (2019). Biosynthesis and Extracellular Concentrations of N,N-dimethyltryptamine (DMT) in Mammalian Brain. Scientific Reports, 9(1), 9333. https://doi.org/10.1038/s41598-019-45812-w
Page 135. However, natural and some synthetic.
924. McClure-Begley, T. D., & Roth, B. L. (2022). The promises and perils of psychedelic pharmacology for psychiatry. Nature Reviews Drug Discovery, 21(6), 463–473. https://doi.org/10.1038/s41573-022-00421-7
925. Marks, M., & Cohen, I. G. (2021). Psychedelic therapy: a roadmap for wider acceptance and utilization. Nature Medicine, 27(10), 1669–1671. https://doi.org/10.1038/s41591-021-01530-3
926. Kwan, A. C., Olson, D. E., Preller, K. H., & Roth, B. L. (2022). The neural basis of psychedelic action. Nature Neuroscience, 25(11), 1407–1419. https://doi.org/10.1038/s41593-022-01177-4
927. McGuire, A. L., Lynch, H. F., Grossman, L. A., & Cohen, I. G. (2023). Pressing regulatory challenges for psychedelic medicine. Science, 380(6643), 347–350. https://doi.org/10.1126/science.adg1324
928. Pollan, M. (2019). How to change your mind: What the new science of psychedelics teaches us about consciousness, dying, addiction, depression, and transcendence. Penguin.
Page 136. A small placebo-controlled trial using ayahuasca.
929. Palhano-Fontes, F., Barreto, D., Onias, H., Andrade, K. C., Novaes, M. M., Pessoa, J. A., Mota-Rolim, S. A., Osório, F. L., Sanches, R., dos Santos, R. G., Tófoli, L. F., de Oliveira Silveira, G., Yonamine, M., Riba, J., Santos, F. R., Silva-Junior, A. A., Alchieri, J. C., Galvão-Coelho, N. L., Lobão-Soares, B., … Araújo, D. B. (2019). Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial. Psychological Medicine, 49(4), 655–663. https://doi.org/10.1017/S0033291718001356
Page 136. LSD showed great promise.
930. Krebs, T. S., & Johansen, P.-Ø. (2012). Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. Journal of Psychopharmacology, 26(7), 994–1002. https://doi.org/10.1177/0269881112439253
Page 136. Up until 2022.
931. Johnson, M. W., Garcia-Romeu, A., Cosimano, M. P., & Griffiths, R. R. (2014). Pilot study of the 5-HT 2A R agonist psilocybin in the treatment of tobacco addiction. Journal of Psychopharmacology, 28(11), 983–992. https://doi.org/10.1177/0269881114548296
932. Bogenschutz, M. P., Podrebarac, S. K., Duane, J. H., Amegadzie, S. S., Malone, T. C., Owens, L. T., Ross, S., & Mennenga, S. E. (2018). Clinical Interpretations of Patient Experience in a Trial of Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder. Frontiers in Pharmacology, 9. https://doi.org/10.3389/fphar.2018.00100
Page 137. Then in September 2022.
933. O’Donnell, K. C., Mennenga, S. E., Owens, L. T., Podrebarac, S. K., Baron, T., Rotrosen, J., Ross, S., Forcehimes, A. A., & Bogenschutz, M. P. (2022). Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial. Contemporary Clinical Trials, 123, 106976. https://doi.org/10.1016/j.cct.2022.106976
934. Bogenschutz, M. P., Ross, S., Bhatt, S., Baron, T., Forcehimes, A. A., Laska, E., Mennenga, S. E., O’Donnell, K., Owens, L. T., Podrebarac, S., Rotrosen, J., Tonigan, J. S., & Worth, L. (2022). Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder. JAMA Psychiatry, 79(10), 953. https://doi.org/10.1001/jamapsychiatry.2022.2096
Page 137. Crucially, we now know.
935. Tsai, G., & Coyle, J. T. (1998). The Role of Glutamatergic Neurotransmission in the Pathophysiology of Alcoholism. Annual Review of Medicine, 49(1), 173–184. https://doi.org/10.1146/annurev.med.49.1.173
936. Moussawi, K., & Kalivas, P. W. (2010). Group II metabotropic glutamate receptors (mGlu2/3) in drug addiction. European Journal of Pharmacology, 639(1–3), 115–122. https://doi.org/10.1016/j.ejphar.2010.01.030
937. Meinhardt, M. W., Hansson, A. C., Perreau-Lenz, S., Bauder-Wenz, C., Stählin, O., Heilig, M., Harper, C., Drescher, K. U., Spanagel, R., & Sommer, W. H. (2013). Rescue of Infralimbic mGluR 2 Deficit Restores Control Over Drug-Seeking Behavior in Alcohol Dependence. The Journal of Neuroscience, 33(7), 2794–2806. https://doi.org/10.1523/JNEUROSCI.4062-12.2013
Page 138. These glutamate receptors.
938. Meinhardt, M. W., Pfarr, S., Fouquet, G., Rohleder, C., Meinhardt, M. L., Barroso-Flores, J., Hoffmann, R., Jeanblanc, J., Paul, E., Wagner, K., Hansson, A. C., Köhr, G., Meier, N., von Bohlen und Halbach, O., Bell, R. L., Endepols, H., Neumaier, B., Schönig, K., Bartsch, D., … Sommer, W. H. (2021). Psilocybin targets a common molecular mechanism for cognitive impairment and increased craving in alcoholism. Science Advances, 7(47). https://doi.org/10.1126/sciadv.abh2399
939. Meinhardt, M. W., & Sommer, W. H. (2023). Schrooms against booze: Potential of mycotherapy for the treatment of AUD. Neuropsychopharmacology, 48(1), 211–212. https://doi.org/10.1038/s41386-022-01446-7
940. González-Maeso, J., Ang, R. L., Yuen, T., Chan, P., Weisstaub, N. v., López-Giménez, J. F., Zhou, M., Okawa, Y., Callado, L. F., Milligan, G., Gingrich, J. A., Filizola, M., Meana, J. J., & Sealfon, S. C. (2008). Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature, 452(7183), 93–97. https://doi.org/10.1038/nature06612
941. Benneyworth, M. A., Xiang, Z., Smith, R. L., Garcia, E. E., Conn, P. J., & Sanders-Bush, E. (2007). A Selective Positive Allosteric Modulator of Metabotropic Glutamate Receptor Subtype 2 Blocks a Hallucinogenic Drug Model of Psychosis. Molecular Pharmacology, 72(2), 477–484. https://doi.org/10.1124/mol.107.035170
Page 138. For some people. Note that the association between psychedelic use and certain mental health disorders most recently was found to be weak. Note as well that there is one study proposing use of psychedelics to treat schizophrenia.
942. Huber, B. (n.d.). What do we know about the risks of psychedelics? Michael Pollan. Retrieved October 6, 2023, from https://michaelpollan.com/psychedelics-risk-today/ 943. Smith, D. G. (2023, February 20). Psychedelics Are a Promising Therapy, but They Can Be Dangerous for Some. The New York Times. 944. Lebedev, A. v., Acar, K., Garzón, B., Almeida, R., Råback, J., Åberg, A., Martinsson, S., Olsson, A., Louzolo, A., Pärnamets, P., Lövden, M., Atlas, L., Ingvar, M., & Petrovic, P. (2021). Psychedelic drug use and schizotypy in young adults. Scientific Reports, 11(1), 15058. https://doi.org/10.1038/s41598-021-94421-z 945. Morton, E., Sakai, K., Ashtari, A., Pleet, M., Michalak, E. E., & Woolley, J. (2023). Risks and benefits of psilocybin use in people with bipolar disorder: An international web-based survey on experiences of ‘magic mushroom’ consumption. Journal of Psychopharmacology, 37(1), 49–60. https://doi.org/10.1177/02698811221131997 946. Bender, D., & Hellerstein, D. J. (2022). Assessing the risk–benefit profile of classical psychedelics: a clinical review of second-wave psychedelic research. Psychopharmacology, 239(6), 1907–1932. https://doi.org/10.1007/s00213-021-06049-6 947. Yaden, D. B., Potash, J. B., & Griffiths, R. R. (2022). Preparing for the Bursting of the Psychedelic Hype Bubble. JAMA Psychiatry, 79(10), 943. https://doi.org/10.1001/jamapsychiatry.2022.2546 948. Wolf, G., Singh, S., Blakolmer, K., Lerer, L., Lifschytz, T., Heresco-Levy, U., Lotan, A., & Lerer, B. (2023). Could psychedelic drugs have a role in the treatment of schizophrenia? Rationale and strategy for safe implementation. Molecular Psychiatry, 28(1), 44–58. https://doi.org/10.1038/s41380-022-01832-z
Page 138. As I’ve pointed out.
949. Narby, J., & Pizuri, R. C. (2021). Plant teachers: Ayahuasca, tobacco, and the pursuit of knowledge. New World Library.
Chapter 7. Caffeine and Nicotine
Page 139. At lower doses.
950. Lieberman, H. R., Wurtman, R. J., Emde, G. G., Roberts, C., & Coviella, I. L. (1987). The effects of low doses of caffeine on human performance and mood. Psychopharmacology, 92(3), 308–312. https://doi.org/10.1007/BF00210835
952. Tverdal, A., Selmer, R., Cohen, J. M., & Thelle, D. S. (2020). Coffee consumption and mortality from cardiovascular diseases and total mortality: Does the brewing method matter? Eur. J. Prev. Cardiol., 27(18), 1986–1993. https://doi.org/10.1177/2047487320914443
954. van Dusseldorp, M., Katan, M. B., van Vliet, T., Demacker, P. N., & Stalenhoef, A. F. (1991). Cholesterol-raising factor from boiled coffee does not pass a paper filter. Arterioscler. Thromb., 11(3), 586–593. https://doi.org/10.1161/01.atv.11.3.586
955. Weusten-Van der Wouw, M. P., Katan, M. B., Viani, R., Huggett, A. C., Liardon, R., Liardon, R., Lund-Larsen, P. G., Thelle, D. S., Ahola, I., & Aro, A. (1994). Identity of the cholesterol-raising factor from boiled coffee and its effects on liver function enzymes. J. Lipid Res., 35, 721–733. https://www.ncbi.nlm.nih.gov/pubmed/7911820
Page 140. The offending terpenoids.
956. Weusten-Van der Wouw, M. P., Katan, M. B., Viani, R., Huggett, A. C., Liardon, R., Liardon, R., Lund-Larsen, P. G., Thelle, D. S., Ahola, I., & Aro, A. (1994). Identity of the cholesterol-raising factor from boiled coffee and its effects on liver function enzymes. J. Lipid Res., 35, 721–733. https://www.ncbi.nlm.nih.gov/pubmed/7911820
958. de Roos, B., van Tol, A., Urgert, R., Scheek, L. M., van Gent, T., Buytenhek, R., Princen, H. M., & Katan, M. B. (2000). Consumption of French-press coffee raises cholesteryl ester transfer protein activity levels before LDL cholesterol in normolipidaemic subjects. J. Intern. Med., 248(3), 211–216. https://doi.org/10.1046/j.1365-2796.2000.00728.x
Page 140. The mechanism.
959. Ricketts, M.-L., Boekschoten, M. v., Kreeft, A. J., Hooiveld, G. J. E. J., Moen, C. J. A., Müller, M., Frants, R. R., Kasanmoentalib, S., Post, S. M., Princen, H. M. G., Porter, J. G., Katan, M. B., Hofker, M. H., & Moore, D. D. (2007). The Cholesterol-Raising Factor from Coffee Beans, Cafestol, as an Agonist Ligand for the Farnesoid and Pregnane X Receptors. Molecular Endocrinology, 21(7), 1603–1616. https://doi.org/10.1210/me.2007-0133
Page 140. Scandinavian boiled coffee.
960. Urgert, R., van der Weg, G., Kosmeijer-Schuil, T. G., van de Bovenkamp, P., Hovenier, R., & Katan, M. B. (1995). Levels of the Cholesterol-Elevating Diterpenes Cafestol and Kahweol in Various Coffee Brews. Journal of Agricultural and Food Chemistry, 43(8), 2167–2172. https://doi.org/10.1021/jf00056a039
961. Gross, G., Jaccaud, E., & Huggett, A. C. (1997). Analysis of the content of the diterpenes cafestol and kahweol in coffee brews. Food Chem. Toxicol., 35(6), 547–554. https://doi.org/10.1016/s0278-6915(96)00123-8
963. Ratnayake, W. M., Hollywood, R., O’Grady, E., & Stavric, B. (1993). Lipid content and composition of coffee brews prepared by different methods. Food Chem. Toxicol., 31(4), 263–269. https://doi.org/10.1016/0278-6915(93)90076-b
Page 140. Instead of an absence of evidence.
964. Urgert, R., van der Weg, G., Kosmeijer-Schuil, T. G., van de Bovenkamp, P., Hovenier, R., & Katan, M. B. (1995). Levels of the Cholesterol-Elevating Diterpenes Cafestol and Kahweol in Various Coffee Brews. Journal of Agricultural and Food Chemistry, 43(8), 2167–2172. https://doi.org/10.1021/jf00056a039
Page 140. However, there is a catch.
965. Ratnayake, W. M., Hollywood, R., O’Grady, E., & Stavric, B. (1993). Lipid content and composition of coffee brews prepared by different methods. Food Chem. Toxicol., 31(4), 263–269. https://doi.org/10.1016/0278-6915(93)90076-b
Page 141. Although speculative.
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Page 141. I know what you are going.
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Page 142. A UK study followed.
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Page 142. This study comports.
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Page 142. Finally, there was a big downside.
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Page 142. One explanation is that for most.
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Page 144. Beyond the potential.
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Page 144. Similarly, a large observational.
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Page 144. One candidate is a serotonin.
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Page 144. The chemical can slow.
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Page 144. The two main species cultivated.
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Page 144. It was there that I. Applies to quote that follows in next sentence as well.
Page 145. We don’t know for sure. Citation referred to in the rest of the paragraph as well.
990. Clifford, M. N. (Ed.). (2012). Coffee: botany, biochemistry and production of beans and beverage. Springer Science & Business Media.
Page 145. The root of the word.
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Page 145 and 146. Nathanson discovered this by. The rest of the paragraph and the next three paragraphs rely on this reference as well, including the quotations.
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Page 146. A similar effect was found.
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Page 146. Biologists did just that. In addition this reference also applies to the next paragraph.
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Page 147. In naturally occurring caffeine-bearing.
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Page 147. The coffee berry borer.
999. Cure, J. R., Rodríguez, D., Gutierrez, A. P., & Ponti, L. (2020). The coffee agroecosystem: bio-economic analysis of coffee berry borer control (Hypothenemus hampei). Scientific Reports, 10(1), 12262. https://doi.org/10.1038/s41598-020-68989-x
Page 147. The beetle itself.
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Page 149. Although coffee has a reputation.
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Page 149. However, a more recent study.
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Page 149. Caffeine poses clear downsides.
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Page 150. In studies involving female twins.
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Page 150. Caffeine is perceived as bitter.
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Page 151. Why the difference?
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Page 151. To figure out what is really going on.
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Page 151. Caffeine is a molecular mimic.
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Page 155. So potent is its use.
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Page 156. If this weren’t enough.
1057. Thurston, R., & Fox, P. M. (1972). Inhibition by Nicotine of Emergence of Apanteles congregatus1 from Its Host, the Tobacco Hornworm2.3. Annals of the Entomological Society of America, 65(3), 547–550. https://doi.org/10.1093/aesa/65.3.547
1058. Barbosa, P., Saunders, J. A., Kemper, J., Trumbule, R., Olechno, J., & Martinat, P. (1986). Plant allelochemicals and insect parasitoids effects of nicotine onCotesia congregata (say) (Hymenoptera: Braconidae) andHyposoter annulipes (Cresson) (Hymenoptera: Ichneumonidae). Journal of Chemical Ecology, 12(6), 1319–1328. https://doi.org/10.1007/BF01012351
1059. Barbosa, P., Gross, P., & Kemper, J. (1991). Influence of Plant Allelochemicals on the Tobacco Hornworm and its Parasitoid, Cotesia Congregata. Ecology, 72(5), 1567–1575. https://doi.org/10.2307/1940956
1060. Garvey, M., Bredlau, J., Kester, K., Creighton, C., & Kaplan, I. (2021). Toxin or medication? Immunotherapeutic effects of nicotine on a specialist caterpillar. Functional Ecology, 35(3), 614–626. https://doi.org/10.1111/1365-2435.13743
Page 156. Human evidence of tobacco.
1061. Duke, D., Wohlgemuth, E., Adams, K. R., Armstrong-Ingram, A., Rice, S. K., & Young, D. C. (2021). Earliest evidence for human use of tobacco in the Pleistocene Americas. Nature Human Behaviour, 6(2), 183–192. https://doi.org/10.1038/s41562-021-01202-9
Page 156. Previously, the oldest evidence.
1062. Carmody, S., Davis, J., Tadi, S., Sharp, J. S., Hunt, R. K., & Russ, J. (2018). Evidence of tobacco from a Late Archaic smoking tube recovered from the Flint River site in southeastern North America. Journal of Archaeological Science: Reports, 21, 904–910. https://doi.org/10.1016/j.jasrep.2018.05.013
Page 156. Tartar from both.
1063. Eerkens, J. W., Tushingham, S., Brownstein, K. J., Garibay, R., Perez, K., Murga, E., Kaijankoski, P., Rosenthal, J. S., & Gang, D. R. (2018). Dental calculus as a source of ancient alkaloids: Detection of nicotine by LC-MS in calculus samples from the Americas. Journal of Archaeological Science: Reports, 18, 509–515. https://doi.org/10.1016/j.jasrep.2018.02.004
Page 156 and 157. The hair of a baby.
1064. Niemeyer, H. M., de Souza, P., Camilo, C., & Echeverría, J. (2018). Chemical evidence of prehistoric passive tobacco consumption by a human perinate (early Formative Period, South-Central Andes). Journal of Archaeological Science, 100, 130–138. https://doi.org/10.1016/j.jas.2018.10.010
Page 157 and 158. Independently, tobacco in the form of pituri. The next three paragraphs are based on the references below.
1066. Johnston, T. H., & Cleland, J. B. (1933). The History of the Aboriginal Narcotic, Pituri. Oceania, 4(2), 201–223. http://www.jstor.org/stable/40327460
1067. Watson, P. L., Luanratana, O., & Griffin, W. J. (1983). The ethnopharmacology of pituri. Journal of Ethnopharmacology, 8(3), 303–311. https://doi.org/10.1016/0378-8741(83)90067-3
1068. Ratsch, A., Steadman, K. J., & Bogossian, F. (2010). The pituri story: a review of the historical literature surrounding traditional Australian Aboriginal use of nicotine in Central Australia. Journal of Ethnobiology and Ethnomedicine, 6(1), 26. https://doi.org/10.1186/1746-4269-6-26
1069. Keogh, L. (2011). Duboisia Pituri: A Natural History. Historical Records of Australian Science, 22(2), 199. https://doi.org/10.1071/HR11008
1070. Moghbel, N., Ryu, B., Ratsch, A., & Steadman, K. J. (2017). Nicotine alkaloid levels, and nicotine to nornicotine conversion, in Australian Nicotiana species used as chewing tobacco. Heliyon, 3(11), e00469. https://doi.org/10.1016/j.heliyon.2017.e00469
Page 158. There is even. The quote by Spencer and Gillen is mentioned by Ratsch et al.
1071. Ratsch, A., Steadman, K. J., & Bogossian, F. (2010). The pituri story: a review of the historical literature surrounding traditional Australian Aboriginal use of nicotine in Central Australia. Journal of Ethnobiology and Ethnomedicine, 6(1), 26. https://doi.org/10.1186/1746-4269-6-26
1072. Spencer, B., & Gillen, F. J. (1898). The native tribes of Central Australia. Macmillan and Company, limited.
Page 159. Zooming out. This reference supports the next paragraph as well.
1076. Reitsma, M. B., Kendrick, P. J., Ababneh, E., Abbafati, C., Abbasi-Kangevari, M., Abdoli, A., Abedi, A., Abhilash, E. S., Abila, D. B., Aboyans, V., Abu-Rmeileh, N. M. E., Adebayo, O. M., Advani, S. M., Aghaali, M., Ahinkorah, B. O., Ahmad, S., Ahmadi, K., Ahmed, H., Aji, B., … Gakidou, E. (2021). Spatial, temporal, and demographic patterns in prevalence of smoking tobacco use and attributable disease burden in 204 countries and territories, 1990–2019: a systematic analysis from the Global Burden of Disease Study 2019. Lancet, 397(10292), 2337–2360. https://doi.org/10.1016/S0140-6736(21)01169-7
Page 160. I smoked just one a day.
1077. Obama, B. (2020). A promised land. Crown, Penguin Random House.
Page 160. Once the coughing subsided.
1078. Pomerleau, C. S., & Pomerleau, O. F. (1992). Euphoriant effects of nicotine in smokers. Psychopharmacology, 108(4), 460–465. https://doi.org/10.1007/BF02247422
Page 160. Of course, I knew.
1079. Hackshaw, A., Morris, J. K., Boniface, S., Tang, J.-L., & Milenković, D. (2018). Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports. BMJ, j5855. https://doi.org/10.1136/bmj.j5855
1080. Moylan, S., Jacka, F. N., Pasco, J. A., & Berk, M. (2013). How cigarette smoking may increase the risk of anxiety symptoms and anxiety disorders: a critical review of biological pathways. Brain and Behavior, 3(3), 302–326. https://doi.org/10.1002/brb3.137
Page 160. A major difference.
1081. Csordas, A., & Bernhard, D. (2013). The biology behind the atherothrombotic effects of cigarette smoke. Nature Reviews Cardiology, 10(4), 219–230. https://doi.org/10.1038/nrcardio.2013.8
1083. Benowitz, N. L., & Burbank, A. D. (2016). Cardiovascular toxicity of nicotine: Implications for electronic cigarette use. Trends Cardiovasc. Med., 26(6), 515–523. https://doi.org/10.1016/j.tcm.2016.03.001
1084. Lee, H.-W., Park, S.-H., Weng, M.-W., Wang, H.-T., Huang, W. C., Lepor, H., Wu, X.-R., Chen, L.-C., & Tang, M.-S. (2018). E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proc. Natl. Acad. Sci. U. S. A., 115(7), E1560–E1569. https://doi.org/10.1073/pnas.1718185115
Page 161. E-cigarette use.
1085. Xie, W., Kathuria, H., Galiatsatos, P., Blaha, M. J., Hamburg, N. M., Robertson, R. M., Bhatnagar, A., Benjamin, E. J., & Stokes, A. C. (2020). Association of Electronic Cigarette Use With Incident Respiratory Conditions Among US Adults From 2013 to 2018. JAMA Netw Open, 3(11), e2020816. https://doi.org/10.1001/jamanetworkopen.2020.20816
1086. Young, R. P., & Scott, R. J. (2020). Inhaled nicotine and lung cancer: Potential role of the nicotinic acetylcholine receptor. Proc. Natl. Acad. Sci. U. S. A., 117(9), 4460–4461. https://doi.org/10.1073/pnas.1921567117
1087. Garcia-Arcos, I., Geraghty, P., Baumlin, N., Campos, M., Dabo, A. J., Jundi, B., Cummins, N., Eden, E., Grosche, A., Salathe, M., & Foronjy, R. (2016). Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner. Thorax, 71(12), 1119–1129. https://doi.org/10.1136/thoraxjnl-2015-208039
Page 161. The longer-term effects.
1088. National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Board on Population Health and Public Health Practice, and Committee on the Review of the Health Effects of Electronic Nicotine Delivery Systems. (2018). Public Health Consequences of E-Cigarettes. National Academies Press.
1090. Grando, S. A. (2014). Connections of nicotine to cancer. Nat. Rev. Cancer, 14(6), 419–429. https://doi.org/10.1038/nrc3725
Page 162. One of the more. This reference supports the next paragraph as well.
1091. Tang, M.-S., Wu, X.-R., Lee, H.-W., Xia, Y., Deng, F.-M., Moreira, A. L., Chen, L.-C., Huang, W. C., & Lepor, H. (2019). Electronic-cigarette smoke induces lung adenocarcinoma and bladder urothelial hyperplasia in mice. Proc. Natl. Acad. Sci. U. S. A., 116(43), 21727–21731. https://doi.org/10.1073/pnas.1911321116
Page 162. Mutations in the DNA.
1092. Gerstung, M., Jolly, C., Leshchiner, I., Dentro, S. C., Gonzalez, S., Rosebrock, D., Mitchell, T. J., Rubanova, Y., Anur, P., Yu, K., Tarabichi, M., Deshwar, A., Wintersinger, J., Kleinheinz, K., Vázquez-García, I., Haase, K., Jerman, L., Sengupta, S., Macintyre, G., … Consortium, P. (2020). The evolutionary history of 2,658 cancers. Nature, 578(7793), 122–128. https://doi.org/10.1038/s41586-019-1907-7
1093. Lee, H.-W., Park, S.-H., Weng, M.-W., Wang, H.-T., Huang, W. C., Lepor, H., Wu, X.-R., Chen, L.-C., & Tang, M.-S. (2018). E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells. Proc. Natl. Acad. Sci. U. S. A., 115(7), E1560–E1569. https://doi.org/10.1073/pnas.1718185115
1094. Shahab, L., Goniewicz, M. L., Blount, B. C., Brown, J., McNeill, A., Alwis, K. U., Feng, J., Wang, L., & West, R. (2017). Nicotine, Carcinogen, and Toxin Exposure in Long-Term E-Cigarette and Nicotine Replacement Therapy Users: A Cross-sectional Study. Ann. Intern. Med., 166(6), 390–400. https://doi.org/10.7326/M16-1107
Page 162. Because other studies.
1095. Haussmann, H.-J., & Fariss, M. W. (2016). Comprehensive review of epidemiological and animal studies on the potential carcinogenic effects of nicotine per se. Crit. Rev. Toxicol., 46(8), 701–734. https://doi.org/10.1080/10408444.2016.1182116
Page 162. Despite the negatives.
1096. Godwin-Austen, R. B., Lee, P. N., Marmot, M. G., & Stern, G. M. (1982). Smoking and Parkinson’s disease. Journal of Neurology, Neurosurgery & Psychiatry, 45(7), 577–581. https://doi.org/10.1136/jnnp.45.7.577
1097. Quik, M., & Jeyarasasingam, G. (2000). Nicotinic receptors and Parkinson’s disease. European Journal of Pharmacology, 393(1–3), 223–230. https://doi.org/10.1016/S0014-2999(99)00888-2
1098. Li, X., Li, W., Liu, G., Shen, X., & Tang, Y. (2015). Association between cigarette smoking and Parkinson’s disease: A meta-analysis. Archives of Gerontology and Geriatrics, 61(3), 510–516. https://doi.org/10.1016/j.archger.2015.08.004
1099. Mappin-Kasirer, B., Pan, H., Lewington, S., Kizza, J., Gray, R., Clarke, R., & Peto, R. (2020). Tobacco smoking and the risk of Parkinson disease. Neurology, 94(20), e2132–e2138. https://doi.org/10.1212/WNL.0000000000009437
PAGE 162 AND 163. A small clinical study.
1100. Oertel, W. H., Müller, H.-H., Unger, M. M., Schade-Brittinger, C., Balthasar, K., Articus, K., Brinkman, M., Venuto, C. S., Tracik, F., Eberling, J., Eggert, K. M., Kamp, C., Kieburtz, K., & Boyd, J. T. (2023). Transdermal Nicotine Treatment and Progression of Early Parkinson’s Disease. NEJM Evidence, 2(9). https://doi.org/10.1056/EVIDoa2200311
Page 163. Remarkably, increased consumption.
1101. Nielsen, S. S., Franklin, G. M., Longstreth, W. T., Swanson, P. D., & Checkoway, H. (2013). Nicotine from edible Solanaceae and risk of Parkinson disease. Annals of Neurology, 74(3), 472–477. https://doi.org/10.1002/ana.23884
1102. Domino, E. F., Hornbach, E., & Demana, T. (1993). The Nicotine Content of Common Vegetables. New England Journal of Medicine, 329(6), 437–437. https://doi.org/10.1056/NEJM199308053290619
Page 163. It isn’t just the human.
1103. Baracchi, D., Marples, A., Jenkins, A. J., Leitch, A. R., & Chittka, L. (2017). Nicotine in floral nectar pharmacologically influences bumblebee learning of floral features. Scientific Reports, 7(1), 1951. https://doi.org/10.1038/s41598-017-01980-1
Page 163. Significantly, some of these genetic variants.
1104. Amos, C. I., Wu, X., Broderick, P., Gorlov, I. P., Gu, J., Eisen, T., Dong, Q., Zhang, Q., Gu, X., Vijayakrishnan, J., Sullivan, K., Matakidou, A., Wang, Y., Mills, G., Doheny, K., Tsai, Y.-Y., Chen, W. V., Shete, S., Spitz, M. R., & Houlston, R. S. (2008). Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nature Genetics, 40(5), 616–622. https://doi.org/10.1038/ng.109
Page 163. This study was repeated in Denmark.
1105. Kaur-Knudsen, D., Bojesen, S. E., Tybjærg-Hansen, A., & Nordestgaard, B. G. (2011). Nicotinic Acetylcholine Receptor Polymorphism, Smoking Behavior, and Tobacco-Related Cancer and Lung and Cardiovascular Diseases: A Cohort Study. Journal of Clinical Oncology, 29(21), 2875–2882. https://doi.org/10.1200/JCO.2010.32.9870
Page 163. The mutation in the rarer.
1106. Bierut, L. J., Stitzel, J. A., Wang, J. C., Hinrichs, A. L., Grucza, R. A., Xuei, X., Saccone, N. L., Saccone, S. F., Bertelsen, S., Fox, L., Horton, W. J., Breslau, N., Budde, J., Cloninger, C. R., Dick, D. M., Foroud, T., Hatsukami, D., Hesselbrock, V., Johnson, E. O., … Goate, A. M. (2008). Variants in nicotinic receptors and risk for nicotine dependence. Am. J. Psychiatry, 165(9), 1163–1171. https://doi.org/10.1176/appi.ajp.2008.07111711
Page 163. A study of thousands. These references supports the next paragraph as well.
1107. Loukola, A., Buchwald, J., Gupta, R., Palviainen, T., Hällfors, J., Tikkanen, E., Korhonen, T., Ollikainen, M., Sarin, A.-P., Ripatti, S., Lehtimäki, T., Raitakari, O., Salomaa, V., Rose, R. J., Tyndale, R. F., & Kaprio, J. (2015). A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism. PLOS Genetics, 11(9), e1005498. https://doi.org/10.1371/journal.pgen.1005498
1108. Sofuoglu, M., Herman, A. I., Nadim, H., & Jatlow, P. (2012). Rapid nicotine clearance is associated with greater reward and heart rate increases from intravenous nicotine. Neuropsychopharmacology, 37(6), 1509–1516. https://doi.org/10.1038/npp.2011.336
Page 164. Fast nicotine metabolizers. This reference applies to the next paragraph as well.
1109. Lerman, C., Schnoll, R. A., Hawk Jr, L. W., Cinciripini, P., George, T. P., Wileyto, E. P., Swan, G. E., Benowitz, N. L., Heitjan, D. F., Tyndale, R. F., & Group, P.-P. R. (2015). Use of the nicotine metabolite ratio as a genetically informed biomarker of response to nicotine patch or varenicline for smoking cessation: a randomised, double-blind placebo-controlled trial. Lancet Respir Med, 3(2), 131–138. https://doi.org/10.1016/S2213-2600(14)70294-2
Chapter 8. Devil’s Breath and Silent Death
Page 166. Quote from William Shakespeare’s Antony and Cleopatra, Act 1. Scene 5.
1111. Bockmann, T., Sanches, M. (2022). Love Addiction. In: Pontes, H.M. (eds) Behavioral Addictions. Studies in Neuroscience, Psychology and Behavioral Economics. Springer, Cham. https://doi.org/10.1007/978-3-031-04772-5_6
1112. Fisher, H. (2005). Why we love: The nature and chemistry of romantic love. Macmillan.
Page 167. In medieval Europe.
1113. Dafni, A., Blanché, C., Khatib, S. A., Petanidou, T., Aytaç, B., Pacini, E., Kohazurova, E., Geva-Kleinberger, A., Shahvar, S., Dajic, Z., Klug, H. W., & Benítez, G. (2021). In search of traces of the mandrake myth: the historical, and ethnobotanical roots of its vernacular names. Journal of Ethnobiology and Ethnomedicine, 17(1), 68. https://doi.org/10.1186/s13002-021-00494-5
1114. Chidiac, E. J., Kaddoum, R. N., & Fuleihan, S. F. (2012). Mandragora: anesthetic of the ancients. Anesthesia & Analgesia, 115(6), 1437–1441. https://doi.org/10.1213/ANE.0b013e318259ee4d
1115. Fatur, K. (2020). “Hexing Herbs” in Ethnobotanical Perspective: A Historical Review of the Uses of Anticholinergic Solanaceae Plants in Europe. Economic Botany, 74(2), 140–158. https://doi.org/10.1007/s12231-020-09498-w
Page 167. Scopolamine produces. Quote from reference below.
1117. Logan, J. C. (1905). The Use of Scopolamine in Anæsthesia. The American Journal of Nursing, 6(3), 166. https://doi.org/10.2307/3403145
1118. Soban, D., Ruprecht, J., Keys, T. E., & Schneck, H. J. (1989). [The history of scopolamine--with special reference to its use in anesthesia]. Anaesthesiologie Und Reanimation, 14(1), 43–54.
1119. Scholtz, S., MacMorris, L., Krogmann, F., & Auffarth, G. U. (2019). Poisons, Drugs and Medicine: On the Use of Atropine and Scopolamine in Medicine and Ophthalmology: An Historical Review of their Applications. (2019). Journal of Eye Study and Treatment, 2019(01). https://doi.org/10.33513/JEST/1901-13
1121. Ullrich, S. F., Hagels, H., & Kayser, O. (2017). Scopolamine: a journey from the field to clinics. Phytochemistry Reviews, 16(2), 333–353. https://doi.org/10.1007/s11101-016-9477-x
1122. World Health Organization. (2021). World Health Organization model list of essential medicines: 22nd list (2021). World Health Organization. https://iris.who.int/handle/10665/345533
Page 167. Scopolamine is an anticolinergic drug.
1123. Spinks, A., & Wasiak, J. (2011). Scopolamine (hyoscine) for preventing and treating motion sickness. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD002851.pub4
Page 167. People around the world.
1124. Benítez, G., March-Salas, M., Villa-Kamel, A., Cháves-Jiménez, U., Hernández, J., Montes-Osuna, N., Moreno-Chocano, J., & Cariñanos, P. (2018). The genus Datura L. (Solanaceae) in Mexico and Spain – Ethnobotanical perspective at the interface of medical and illicit uses. Journal of Ethnopharmacology, 219, 133–151. https://doi.org/10.1016/j.jep.2018.03.007
1125. Griffin, W. J., & Lin, G. D. (2000). Chemotaxonomy and geographical distribution of tropane alkaloids. Phytochemistry, 53(6), 623–637. https://doi.org/10.1016/S0031-9422(99)00475-6
1126. Bussmann, R. W., & Sharon, D. (2006). Traditional medicinal plant use in Northern Peru: tracking two thousand years of healing culture. Journal of Ethnobiology and Ethnomedicine, 2(1), 47. https://doi.org/10.1186/1746-4269-2-47
1127. Bennett, B. C. (1992). Hallucinogenic Plants of the Shuar and Related Indigenous Groups in Amazonian Ecuador and Peru. Brittonia, 44(4), 483. https://doi.org/10.2307/2807199
1129. Litzinger, W. J. (1981). Ceramic evidence for prehistoric datura use in North America. Journal of Ethnopharmacology, 4(1), 57–74. https://doi.org/10.1016/0378-8741(81)90020-9
1132. Alves, M. N., Sartoratto, A., & Trigo, J. R. (2007). Scopolamine in Brugmansia Suaveolens (Solanaceae): Defense, Allocation, Costs, and Induced Response. Journal of Chemical Ecology, 33(2), 297–309. https://doi.org/10.1007/s10886-006-9214-9
1133. Algradi, A. M., Liu, Y., Yang, B.-Y., & Kuang, H.-X. (2021). Review on the genus Brugmansia: Traditional usage, phytochemistry, pharmacology, and toxicity. Journal of Ethnopharmacology, 279, 113910. https://doi.org/10.1016/j.jep.2021.113910
1134. Pinto, C. F., Salinas, S., Flores-Prado, L., Echeverría, J., & Niemeyer, H. M. (2016). Sequestration of tropane alkaloids from Brugmansia suaveolens (Solanaceae) by the treehopper Alchisme grossa (Hemiptera: Membracidae). Biochemical Systematics and Ecology, 66, 161–165. https://doi.org/10.1016/j.bse.2016.03.015
Page 168. Some species of Duboisia.
1135. Kohnen, K. L., Sezgin, S., Spiteller, M., Hagels, H., & Kayser, O. (2018). Localization and Organization of Scopolamine Biosynthesis in Duboisia myoporoides R. Br. Plant and Cell Physiology, 59(1), 107–118. https://doi.org/10.1093/pcp/pcx165
Page 169. Most species of Brugsmansia.
1136. Dupin, J., & Smith, S. D. (2019). Integrating historical biogeography and environmental niche evolution to understand the geographic distribution of Datureae. American Journal of Botany, 106(5), 667–678. https://doi.org/10.1002/ajb2.1281
Page 169. The huge white.
1137. Soteras, F., Moré, M., Ibañez, A. C., Iglesias, M. del R., & Cocucci, A. A. (2018). Range overlap between the sword-billed hummingbird and its guild of long-flowered species: An approach to the study of a coevolutionary mosaic. PLOS ONE, 13(12), e0209742. https://doi.org/10.1371/journal.pone.0209742
1138. Kite, G. C., & Leon, C. (1995). Volatile compounds emitted from flowers and leaves of Brugmansia × candida (Solanaceae). Phytochemistry, 40(4), 1093–1095. https://doi.org/10.1016/0031-9422(95)00485-P
1139. Alves, M. N., Sartoratto, A., & Trigo, J. R. (2007). Scopolamine in Brugmansia Suaveolens (Solanaceae): Defense, Allocation, Costs, and Induced Response. Journal of Chemical Ecology, 33(2), 297–309. https://doi.org/10.1007/s10886-006-9214-9
Page 169. The Zuni Pueblo.
1140. Doelle, W. H. (2009). Zuni origins: toward a new synthesis of Southwestern archaeology. University of Arizona Press.
1141. Kintigh, K. W., Glowacki, D. M., & Huntley, D. L. (2004). Long-Term Settlement History and the Emergence of Towns in the Zuni Area. American Antiquity, 69(3), 432–456. https://doi.org/10.2307/4128401
1143. Stevenson, M. C. (1915). Ethnobotany of the Zuni Indians (Vol. 30). US Government Printing Office.
Page 169. Such use presaged.
1144. Störck, A. (1762). Libellus, quo demonstratur: stramonium, hyosciamum, aconitum. typis Joannis Thomae Trattner.
Page 169. The use of Hyoscyamus.
1145. Ullrich, S. F., Hagels, H., & Kayser, O. (2017). Scopolamine: a journey from the field to clinics. Phytochemistry Reviews, 16(2), 333–353. https://doi.org/10.1007/s11101-016-9477-x
1149. Goerig, M. (2014). The Development of Anaesthesiology in German-Speaking Countries. In The Wondrous Story of Anesthesia (pp. 371–389). Springer New York. https://doi.org/10.1007/978-1-4614-8441-7_29
Page 170. By 1902, Austrian physician.
1150. Steinbuchel, V. (1902). Vorlaufige Mittheilung uber die Anwendung von Skopolamin-Morphium-Injectionem in der Geburtshilfe. Zentralbl F Gynak, 26, 1304.
Page 170. Eventually, two German physicians.
1151. Gauss, C. J. (1906). Anwendung des Skopolamin-Morphium Dammerschlafes in der Geburtshilfe. Med Klin, 2, 136-138.
1152. Krönig, P. (1908). Scopolamine-Morphine Narcosis In Labour. The British Medical Journal, 2(2490), 805–808. http://www.jstor.org/stable/25279080
1153. Twilight Sleep: the Dammerschlaf of the Germans. (1915). Canadian Medical Association journal, 5(9), 805–808.
1154. Haultain, F. W., & Swift, B. H. (1916). THE MORPHINE-HYOSCINE METHOD OF PAINLESS CHILDBIRTH: OR SO-CALLED “TWILIGHT SLEEP.”. British Medical Journal, 2(2911), 513–515. https://doi.org/10.1136/bmj.2.2911.513
Page 170. Given that there was generally no safe.
1155. Daniel, M. F. (1914). What Do You Know about Twilight Sleep?. Texas Medical Journal, 30(3), 123.
1157. Leavitt, J. W. (1980). Birthing and Anesthesia: The Debate over Twilight Sleep. Signs, 6(1), 147–164. http://www.jstor.org/stable/3173972
1158. Johnson, B., & Quinlan, M. M. (2015). Technical Versus Public Spheres: A Feminist Analysis of Women’s Rhetoric in the Twilight Sleep Debates of 1914–1916. Health Communication, 30(11), 1076–1088. https://doi.org/10.1080/10410236.2014.921269
1159. Tracy, M., & Leupp, C. (1914). Painless childbirth. McClure Publications, Incorporated.
Page 170. Initially, twilight sleep.
1160. Leavitt, J. W. (1980). Birthing and Anesthesia: The Debate over Twilight Sleep. Signs, 6(1), 147–164. http://www.jstor.org/stable/3173972
Page 170. Scopolamine even moonlighted.
1161. House, R. E. (1931). The Use of Scopolamine in Criminology. The American Journal of Police Science, 2(4), 328. https://doi.org/10.2307/1147361
1166. Lakstygal, A. M., Kolesnikova, T. O., Khatsko, S. L., Zabegalov, K. N., Volgin, A. D., Demin, K. A., Shevyrin, V. A., Wappler-Guzzetta, E. A., & Kalueff, A. v. (2019). DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens. ACS Chemical Neuroscience, 10(5), 2144–2159. https://doi.org/10.1021/acschemneuro.8b00615
1167. Passie, T., & Benzenhöfer, U. (2018). MDA, MDMA, and other “mescaline‐like” substances in the US military’s search for a truth drug (1940s to 1960s). Drug Testing and Analysis, 10(1), 72–80. https://doi.org/10.1002/dta.2292
1168. Widacki, J. (2021). The use of narcoanalysis by Polish counterintelligence in the 1930s. European Polygraph, 15(1), 39–52. https://doi.org/10.2478/ep-2021-0003
Page 170 and 171. Scopolamine derived from Brugmansia.
1169. Lusthof, K. J., Bosman, I. J., Kubat, B., & Vincenten-van Maanen, M. J. (2017). Toxicological results in a fatal and two non-fatal cases of scopolamine-facilitated robberies. Forensic Science International, 274, 79–82. https://doi.org/10.1016/j.forsciint.2017.01.024
1170. Alonso, C. F., Casado, E. D., Jorge, O. Q., Morales, C. M., Serrano, B. B., & Santiago-Sáez, A. (2022). Drug facilitated crimes by “burundanga” or scopolamine. Spanish Journal of Legal Medicine, 48(2), 74–77. https://doi.org/10.1016/j.remle.2022.01.003
1171. Diaz, G. (2015). Toxicosis by Plant Alkaloids in Humans and Animals in Colombia. Toxins, 7(12), 5408–5416. https://doi.org/10.3390/toxins7124892
1172. Reichert, S., Lin, C., Ong, W., Him, C. C., & Hameed, S. (2017). Million dollar ride: Crime committed during involuntary scopolamine intoxication. Canadian Family Physician Medecin de Famille Canadien, 63(5), 369–370.
1177. Uribe-Granja, M. G., Moreno-López, C. L., Zamora-Suárez, A., & Acosta, P. J. (2005). Perfil epidemiológico de la intoxicación con burundanga en la clínica Uribe Cualla SA de Bogotá, DC. Acta Neurológica Colombiana, 21(3), 197-201.
Page 171. A different urban legend.
1178. Matthiolus, P. (1565). Commentarii pedacii Dioscoridis anazerbi de Materia Medica. Venetiis: Valgarisiana 1074.
1179. Kraemer, H. (1894). Belladonna: A Study of Its History, Action and Uses in Medicine. Johnson & Johnson.
1180. Campbell, E. A. (2007). Don’t Say It with Nightshades: Sentimental Botany and the Natural History of “Atropa Belladonna.” Victorian Literature and Culture, 35(2), 607–615. http://www.jstor.org/stable/40347177
1181. Lee, M. R. (2007). Solanaceae IV: Atropa belladonna, deadly nightshade. The Journal of the Royal College of Physicians of Edinburgh, 37(1), 77–84.
1182. Maurya, V. K., Kumar, S., Kabir, R., Shrivastava, G., Shanker, K., Nayak, D., Khurana, A., Manchanda, R. K., Gadugu, S., Kar, S. K., Verma, A. K., & Saxena, S. K. (2020). Dark Classics in Chemical Neuroscience: An Evidence-Based Systematic Review of Belladonna. ACS Chemical Neuroscience, 11(23), 3937–3954. https://doi.org/10.1021/acschemneuro.0c00413
1183. Forbes, T. R. (1977). Why is it called “beautiful lady”? A note on belladonna. Bulletin of the New York Academy of Medicine, 53(4), 403–406.
1184. Feinsod, M. (2000). The blind beautiful eye. Journal of neuro-ophthalmology, 20(1), 22-24.
1186. Pineles, S. L., Kraker, R. T., VanderVeen, D. K., Hutchinson, A. K., Galvin, J. A., Wilson, L. B., & Lambert, S. R. (2017). Atropine for the Prevention of Myopia Progression in Children. Ophthalmology, 124(12), 1857–1866. https://doi.org/10.1016/j.ophtha.2017.05.032
Page 172. Cocaine is produced.
1187. White, D. M., Huang, J.-P., Jara-Muñoz, O. A., MadriñáN, S., Ree, R. H., & Mason-Gamer, R. J. (2021). The Origins of Coca: Museum Genomics Reveals Multiple Independent Domestications from Progenitor Erythroxylum gracilipes. Systematic Biology, 70(1), 1–13. https://doi.org/10.1093/sysbio/syaa074
Page 172. The question is why coca plants.
1188. Nathanson, J. A., Hunnicutt, E. J., Kantham, L., & Scavone, C. (1993). Cocaine as a naturally occurring insecticide. Proceedings of the National Academy of Sciences, 90(20), 9645–9648. https://doi.org/10.1073/pnas.90.20.9645
Page 173. More recent studies.
1189. Blum, M. S., Rivier, L., & Plowman, T. (1981). Fate of cocaine in the lymantriid Eloria noyesi, a predator of Erythroxylum coca. Phytochemistry, 20(11), 2499–2500. https://doi.org/10.1016/0031-9422(81)83080-4
1190. Kanno, M., Hiramatsu, S., Kondo, S., Tanimoto, H., & Ichinose, T. (2021). Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila. Scientific Reports, 11(1), 3432. https://doi.org/10.1038/s41598-021-82813-0
Page 173. Not surprisingly.
1191. Collenette, C. L. (1950). LXXIX.— A revision of the genus Eloria Walker (Heterocera, Lymantriidæ). Annals and Magazine of Natural History, 3(34), 813–865. https://doi.org/10.1080/00222935008654717
1192. Blum, M. S., Rivier, L., & Plowman, T. (1981). Fate of cocaine in the lymantriid Eloria noyesi, a predator of Erythroxylum coca. Phytochemistry, 20(11), 2499–2500. https://doi.org/10.1016/0031-9422(81)83080-4
1195. Chen, R., Wu, X., Wei, H., Han, D. D., & Gu, H. H. (2006). Molecular cloning and functional characterization of the dopamine transporter from Eloria noyesi, a caterpillar pest of cocaine-rich coca plants. Gene, 366(1), 152–160. https://doi.org/10.1016/j.gene.2005.09.018
Page 173. Cocaine is different. References below apply to the paragraphs through page 174, up to the paragraph that begins with “Cocaine exerts…”
1204. Kilty, J. E., Lorang, D., & Amara, S. G. (1991). Cloning and Expression of a Cocaine-Sensitive Rat Dopamine Transporter. Science, 254(5031), 578–579. https://doi.org/10.1126/science.1948035
1205. Amara, S. G., & Sonders, M. S. (1998). Neurotransmitter transporters as molecular targets for addictive drugs. Drug and Alcohol Dependence, 51(1–2), 87–96. https://doi.org/10.1016/S0376-8716(98)00068-4
1206. Rothman, R. B., Baumann, M. H., Dersch, C. M., Romero, D. v, Rice, K. C., Carroll, F. I., & Partilla, J. S. (2001). Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse, 39(1), 32–41. https://doi.org/https://doi.org/10.1002/1098-2396(20010101)39:1<32::AID-SYN5>3.0.CO;2-3
1208. Kelz, M. B., Chen, J., Carlezon, W. A., Whisler, K., Gilden, L., Beckmann, A. M., Steffen, C., Zhang, Y.-J., Marotti, L., Self, D. W., Tkatch, T., Baranauskas, G., Surmeier, D. J., Neve, R. L., Duman, R. S., Picciotto, M. R., & Nestler, E. J. (1999). Expression of the transcription factor ΔFosB in the brain controls sensitivity to cocaine. Nature, 401(6750), 272–276. https://doi.org/10.1038/45790
Page 174. The situation is the opposite in insects. Note that studies in honeybees do show responses similar to those in humans because cocaine impacts biogenic amine reuptake, which also impacts reward circuits. The hypothesis proposed by Barron et al. referenced below is that “Ecologically, cocaine is an effective plant defence compound via disruption of herbivore motor control but, because the neurochemical systems targeted by cocaine also modulate reward processing, the reinforcing properties of cocaine occur as a `side effect’.”
1209. Nathanson, J. A., Hunnicutt, E. J., Kantham, L., & Scavone, C. (1993). Cocaine as a naturally occurring insecticide. Proceedings of the National Academy of Sciences, 90(20), 9645–9648. https://doi.org/10.1073/pnas.90.20.9645
1211. Roeder, T., Seifert, M., Kähler, C., & Gewecke, M. (2003). Tyramine and octopamine: Antagonistic modulators of behavior and metabolism. Archives of Insect Biochemistry and Physiology, 54(1), 1–13. https://doi.org/10.1002/arch.10102
1212. Barron, A. B., Maleszka, R., Helliwell, P. G., & Robinson, G. E. (2009). Effects of cocaine on honey bee dance behaviour. Journal of Experimental Biology, 212(2), 163–168. https://doi.org/10.1242/jeb.025361
Page 174. The oldest evidence.
1213. Dillehay, T. D., Rossen, J., Ugent, D., Karathanasis, A., Vásquez, V., & Netherly, P. J. (2010). Early Holocene coca chewing in northern Peru. Antiquity, 84(326), 939–953. https://doi.org/10.1017/S0003598X00067004
Page 174. Aymara and Quecha people.
1214. Dillehay, T. D., Rossen, J., Ugent, D., Karathanasis, A., Vásquez, V., & Netherly, P. J. (2010). Early Holocene coca chewing in northern Peru. Antiquity, 84(326), 939–953. https://doi.org/10.1017/S0003598X00067004
1215. Hanna, J. M. (1974). Coca Leaf Use in Southern Peru: Some Biosocial Aspects. American Anthropologist, 76(2), 281–296. http://www.jstor.org/stable/674183
1216. Plowman, T. (1984). The Ethnobotany of Coca (Erythroxylum spp., Erythroxylaceae). Advances in Economic Botany, 1, 62–111. http://www.jstor.org/stable/43931370
1217. Grisaffi, T. (2010). We Are Originarios... “We Just Aren’t from Here”: Coca leaf and Identity Politics in the Chapare, Bolivia. Bulletin of Latin American Research, 29(4), 425–439. http://www.jstor.org/stable/25741493
1218. Toyne, M. (2023). Transformation of Coca to Cocaine: An Overview of Traditional Drug Use and Modern Drug Abuse. The University of Western Ontario Journal of Anthropology, 25(1), 94–115. https://doi.org/10.5206/uwoja.v25i1.16031
Page 175. Either methods of preparation.
1219. Holmstedt, B., Lindgren, J.-E., Rivier, L., & Plowman, T. (1979). Cocaine in blood of coca chewers. Journal of Ethnopharmacology, 1(1), 69–78. https://doi.org/10.1016/0378-8741(79)90017-5
1221. Valdez, L. M., Taboada, J., & Valdez, J. E. (2015). Ancient Use of Coca Leaves in the Peruvian Central Highlands. J. Anthropol. Res., 71(2), 231–258. https://doi.org/10.3998/jar.0521004.0071.204
Page 175. Early in the Spanish.
1222. Biondich, A. S., & Joslin, J. D. (2016). Coca: The History and Medical Significance of an Ancient Andean Tradition. Emerg. Med. Int., 2016, 4048764. https://doi.org/10.1155/2016/4048764
Page 175 and 176. Cocaine as a drug was therefore.
1223. Markel, H. (2012). An Anatomy of Addiction: Sigmund Freud, William Halsted, and the Miracle Drug Cocaine. Vintage.
1226. Marietjie, B. (2012). Coca-Cola : definitely a taste for life! : intellectual property. Without Prejudice, 12(6), 35–37. https://doi.org/10.10520/EJC124417\
Page 176. Nevertheless, some newsarticles.
1227. Gootenberg, P. (2004). Secret Ingredients: The Politics of Coca in US–Peruvian Relations, 1915–65. Journal of Latin American Studies, 36(2), 233–265. https://doi.org/10.1017/S0022216X04007424
1238. Freud, S. (1885). Über coca. M. Perles. Quoted in: Shaffer, H. (1984). Uber coca: Freud’s cocaine discoveries. Journal of Substance Abuse Treatment, 1(3), 205–217. https://doi.org/10.1016/0740-5472(84)90023-0
Page 178. Freud used cocaine.
1239. Markel, H. (2012). An anatomy of addiction: Sigmund Freud, William Halsted, and the miracle drug, cocaine. Vintage.
Page 177. The same year that.
1240. Goerig, M., Bacon, D., & van Zundert, A. (2012). Carl Koller, Cocaine, and Local Anesthesia. Regional Anesthesia and Pain Medicine, 37(3), 318–324. https://doi.org/10.1097/AAP.0b013e31825051f3
Page 177. Cocaine’s use as a local.
1241. Einhorn, A., Fiedler, K., Ladisch, C., & Uhlfelder, E. (1909). Ueber p-Aminobenzoësäurealkaminester. Justus Liebig’s Annalen Der Chemie, 371(2), 142–161. https://doi.org/10.1002/jlac.19093710204
1243. Griffith, H. R., & Johnson, G. E. (1942). The use of curare in general anesthesia. The Journal of The American Society of Anesthesiologists, 3(4), 418-420. https://doi.org/10.1097/00000542-194207000-00006
1244. Dillane, D., Chartrand, D., & Maltby, R. (2017). Harold Griffith’s legacy: a tribute on the 75th anniversary of the introduction of curare into anesthetic practice. Canadian Journal of Anesthesia/Journal Canadien d’anesthésie, 64(6), 559–568. https://doi.org/10.1007/s12630-017-0864-6
1245. Bennett, A. E. (1968). The history of the introduction of curare into medicine. Anesthesia and Analgesia, 47(5), 484–492.
1252. von Humboldt, A., & Bonpland, A. (1852). Personal narrative of travels to the equinoctial regions of America, during the years 1799-1804 (Vol. 2). Henry G. Bohn.
1256. Bisset, N. G. (1992). War and hunting poisons of the New World. Part 1. Notes on the early history of curare. Journal of Ethnopharmacology, 36(1), 1–26. https://doi.org/10.1016/0378-8741(92)90056-W
Page 179. Like cobratoxin.
1257. Lester, H. A. (1972). Vulnerability of desensitized or curare-treated acetylcholine receptors to irreversible blockade by cobra toxin. Molecular Pharmacology, 8(6), 632–644.
Page 179 and 180. In 1935. References below apply to the next three paragraphs.
1258. King, H. (1935). 330. Curare alkaloids. Part I. Tubocurarine. Journal of the Chemical Society (Resumed), 1381. https://doi.org/10.1039/jr9350001381
1259. Gill, R. C. (1940). White water and black magic, Henry Holt.
1265. Smith, S. M., Brown, H. O., Toman, J. E., & Goodman, L. S. (1947). The lack of cerebral effects of d-tubocuarine. Anesthesiology, 8(1), 1–14. https://doi.org/10.1097/00000542-194701000-00001
1266. Plenk, H. P. (1992). Medicine in the Beehive State 1940-1990. Utah Medical Association, 540 East 500 South, Salt Lake City, UT 84102.
1267. Anderson, R. (2010). A TORTURED PATH: Curare’s Journey from Poison Darts to Paralysis by Design. Molecular Interventions, 10(5), 252–258. https://doi.org/10.1124/mi.10.5.1
1269. Allen, G. W. (1953). Black widow spider (Latrodectus mactans) poisoning treated with d-tubocurarine chloride. Annals of Internal Medicine, 39(3), 624–625. https://doi.org/10.7326/0003-4819-39-3-624
Page 181. The Indigenous people who discovered.
1270. Gomes, M. F., & Sampaio, J. A. L. (2019). [Biopiracy and Traditional Knowledge: Faces of Biocolonialism and its Regulation]. Veredas Do Direito: Direito Ambiental e Desenvolvimento Sustentável, 16(34), 91–121. https://doi.org/10.18623/rvd.v16i34.1274
1271. Bruch, K., Stelzer, J., & Hasse, G. (2021). Institutionalizing Biopiracy: Analysis of the Benefit-Sharing Rules in the Brazilian Biodiversity Law. The Journal of Environment & Development, 17.
1272. Bil, G., & Virdi, J. (2022). Special Issue Introduction: Colonial Histories of Plant-Based Pharmaceuticals. History of Pharmacy and Pharmaceuticals, 63(2), 134–148. https://doi.org/10.3368/hopp.63.2.134
1273. Yano, L. I. (1993). Protection of the Ethnobiological Knowledge of Indigenous Peoples. UCLA L. Rev., 41, 443.
1276. Pedrollo, C. T., & Kinupp, V. F. (2015). Sustainability or Colonialism? Legislative obstacles to research and development of natural products and patents on traditional knowledge in Brazil. Acta Botanica Brasilica, 29(3), 452–456. https://doi.org/10.1590/0102-33062015abb0101
Chapter 9. Opioid Overlords
Page 182. On and on they walked. Quote from reference below.
1277. Baum, L. F., & Denslow, W. W. (1900). The Wonderful Wizard of Oz by L. Frank Baum with Pictures by W. W. Denslow. George M. Hill Company.
Page 182. During fieldwork in the Galápagos.
1278. Weeks, A., & Tye, A. (2009). Phylogeography of palo santo trees ( Bursera graveolens and Bursera malacophylla ; Burseraceae) in the Galápagos archipelago. Botanical Journal of the Linnean Society, 161(4), 396–410. https://doi.org/10.1111/j.1095-8339.2009.01008.x
1280. van Beek, G. W. (1960). Frankincense and Myrrh. The Biblical Archaeologist, 23(3), 70–95. https://doi.org/10.2307/3209285
1281. Zviely, M., & Boix-Camps, A. (2015). Sesquiterpenoides-the holy fragrance ingredients. Isr. Chem. Eng., 1, 27-31.
1282. De Feo, V. (1992). Medicinal and magical plants in the northern Peruvian Andes. FITOTERAPIA-MILANO-, 63, 417-417.
1283. Dohling, C. (2008). Boswellia serrata (Frankincense)-from traditional Indian medicine (Ayurveda) to evidence-based medicine. Phytomedicine: International Journal of Phytotherapy & Phytopharmacology, 15(6-7), 540-541.
1284. Bradley, S. (2018). Myrrh: Medical Knowledge from Arabia into Chinese Materia Medica. Medicina nei secoli: Journal of history of medicine and medical humanities, 30(3), 881-906.
1285. Thulin, M., & Per Claeson. (1991). The Botanical Origin of Scented Myrrh (Bissabol or Habak Hadi). Economic Botany, 45(4), 487–494. http://www.jstor.org/stable/4255391
Page 183. The Gospel of St. Mark. Called “vinum murratum” (see reference below by Dolara et al.).
1286. Dolara, P., Luceri, C., Ghelardini, C., Monserrat, C., Aiolli, S., Luceri, F., Lodovici, M., Menichetti, S., & Romanelli, M. N. (1996). Analgesic effects of myrrh. Nature, 379(6560), 29–29. https://doi.org/10.1038/379029a0
Page 183. Extracts from frankincense.
1287. Menon, M., & Kar, A. (1971). Analgesic and psychopharmacological effects of the gum resin of Boswellia serrata. Planta Medica, 19(02), 333–341. https://doi.org/10.1055/s-0028-1099651
Page 183. One of the principal terpenoids.
1288. Moussaieff, A., Rimmerman, N., Bregman, T., Straiker, A., Felder, C. C., Shoham, S., Kashman, Y., Huang, S. M., Lee, H., Shohami, E., Mackie, K., Caterina, M. J., Walker, J. M., Fride, E., & Mechoulam, R. (2008). Incensole acetate, an incense component, elicits psychoactivity by activating TRPV3 channels in the brain. The FASEB Journal, 22(8), 3024–3034. https://doi.org/10.1096/fj.07-101865
Page 183. For example carvacrol.
1289. Vogt‐Eisele, A. K., Weber, K., Sherkheli, M. A., Vielhaber, G., Panten, J., Gisselmann, G., & Hatt, H. (2007). Monoterpenoid agonists of TRPV3. British Journal of Pharmacology, 151(4), 530–540. https://doi.org/10.1038/sj.bjp.0707245
1290. Xu, H., Delling, M., Jun, J. C., & Clapham, D. E. (2006). Oregano, thyme and clove-derived flavors and skin sensitizers activate specific TRP channels. Nature Neuroscience, 9(5), 628–635. https://doi.org/10.1038/nn1692
Page 184. Myrrh is even more remarkable.
1291. Dolara, P., Luceri, C., Ghelardini, C., Monserrat, C., Aiolli, S., Luceri, F., Lodovici, M., Menichetti, S., & Romanelli, M. N. (1996). Analgesic effects of myrrh. Nature, 379(6560), 29–29. https://doi.org/10.1038/379029a0
Page 184. The usual, and incorrect.
1292. Brownstein, M. J. (1993). A brief history of opiates, opioid peptides, and opioid receptors. Proc. Natl. Acad. Sci. U. S. A., 90(12), 5391–5393. https://doi.org/10.1073/pnas.90.12.5391
1293. Neligan, A. R. (1927). The Opium Question: With Special Reference to Persia. John Bale, sons & Danielsson, Limited.
Page 184. However, the ancient Assyrian.
1294. Thompson, R. C. (1924). The Assyrian herbal. Luzac and Company.
Page 184. Other evidence offered. See Krikorian (1975) for details, including the quote from Erica Reiner “No word either…” that he wrote was from a letter that she sent to him.
Page 184 and 185. The first people to cultivate. These references support this paragraph and the next paragraph.
1298. Hammer, K., & Fritsch, R. (1977). The question of ancestral species of cultivated poppy (Papaver somniferum L.). Die Kulturpflanze, 25, 113–124.
1299. Salavert, A., Zazzo, A., Martin, L., Antolín, F., Gauthier, C., Thil, F., Tombret, O., Bouby, L., Manen, C., Mineo, M., Mueller-Bieniek, A., Piqué, R., Rottoli, M., Rovira, N., Toulemonde, F., & Vostrovská, I. (2020). Direct dating reveals the early history of opium poppy in western Europe. Sci. Rep., 10(1), 20263. https://doi.org/10.1038/s41598-020-76924-3
1300. Jesus, A., Bonhomme, V., Evin, A., Ivorra, S., Soteras, R., Salavert, A., Antolín, F., & Bouby, L. (2021). A morphometric approach to track opium poppy domestication. Sci. Rep., 11(1), 9778. https://doi.org/10.1038/s41598-021-88964-4
Page 186. For example, a remarkable kitchen
1301. Peyronel, L., Vacca, A., & Wachter-Sarkady, C. (2014). Food and Drink preparation at Ebla, Syria. New data from the Royal Palace G ( c. 2450-2300 BC). Food and History, 12(3), 3–38. https://doi.org/10.1484/J.FOOD.5.110584
1304. Smith, R. K., Stacey, R. J., Bergström, E., & Thomas-Oates, J. (2018). Detection of opium alkaloids in a Cypriot base-ring juglet. The Analyst, 143(21), 5127–5136. https://doi.org/10.1039/C8AN01040D
Page 186. When opium poppy supplies were running low. Quotation “in all instances…” is from Emboden (1981), referenced below.
1305. Emboden, W. A. (1981). Transcultural use of narcotic water lilies in ancient Egyptian and Maya drug ritual. J. Ethnopharmacol., 3(1), 39–83. https://doi.org/10.1016/0378-8741(81)90013-1
Page 186 and 187. Blue water lilies. The quote “water chaos” is from Emboden (1981). This reference applies to the next paragraph as well.
1306. Emboden, W. A. (1981). Transcultural use of narcotic water lilies in ancient Egyptian and Maya drug ritual. J. Ethnopharmacol., 3(1), 39–83. https://doi.org/10.1016/0378-8741(81)90013-1
Page 187. In chapter 81.
1307. Budge, A.E.W. (1975). The Book of the Dead (The Papyrus of Ani) (pp. 310-311). Crown Publications reprint of the 1920 imprint of the Medici Society.
1309. de Rios, M. D., Alger, N., Crumrine, N. R., Furst, P. T., Harman, R. C., Hellmuth, N. M., Hopkins, N. A., King, W. C., Koss, J. D., La Barre, W., Landar, H. J., Long, J. K., Proskouriakoff, T., Rubel, A. J., Samaranch, F., J. Eric S. Thompson, & Wescott, R. W. (1974). The Influence of Psychotropic Flora and Fauna on Maya Religion [and Comments and Reply]. Current Anthropology, 15(2), 147–164. http://www.jstor.org/stable/2740991
Page 187. In both civilizations.
1310. Emboden, W. A. (1981). Transcultural use of narcotic water lilies in ancient Egyptian and Maya drug ritual. J. Ethnopharmacol., 3(1), 39–83. https://doi.org/10.1016/0378-8741(81)90013-1
Page 187. So similar were the. Quote is from Emboden (1981) below.
1311. Emboden, W. A. (1981). Transcultural use of narcotic water lilies in ancient Egyptian and Maya drug ritual. J. Ethnopharmacol., 3(1), 39–83. https://doi.org/10.1016/0378-8741(81)90013-1
Page 188. We now know.
1312. Diaz, J. L. (1977). Ethnopharmacology of Sacred Psychoactive Plants Used by the Indians of Mexico. Annual Review of Pharmacology and Toxicology, 17(1), 647–675. https://doi.org/10.1146/annurev.pa.17.040177.003243
1313. Emboden, W. A. (1981). Transcultural use of narcotic water lilies in ancient Egyptian and Maya drug ritual. J. Ethnopharmacol., 3(1), 39–83. https://doi.org/10.1016/0378-8741(81)90013-1
1314. Emboden, W. A. (1983). The ethnobotany of the Dresden Codex with especial reference to the narcotic Nymphaea ampla. Botanical Museum Leaflets, Harvard University., 29(2), 87–132. http://www.jstor.org/stable/41762844
1316. Dula, E., Bukofzer, S., Perdok, R., & George, M. (2001). Double-Blind, Crossover Comparison of 3 mg Apomorphine SL with Placebo and with 4 mg Apomorphine SL in Male Erectile Dysfunction. European Urology, 39(5), 558–564. https://doi.org/10.1159/000052503
Page 188. Another water lily alkaloid.
1317. Bhattacharya, S. K., Bose, R., Ghosh, P., Tripathi, V. J., Ray, A. B., & Dasgupta, B. (1978). Psychopharmacological studies on (--)-nuciferine and its Hofmann degradation product atherosperminine. Psychopharmacology, 59(1), 29–33. https://doi.org/10.1007/BF00428026
Page 188. Given the opposing effects.
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Page 196. If mammals did. The rationale for this statement is that mammals are ~300 million years old as a lineage. If we assume that the mammalian crown group synthesized morphinan alkaloids, this would imply that the age is far older than the origin of the angiosperms, which includes the opium poppy, by at ~150 million years.
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Page 199. In laboratory experiments, fruit flies.
1392. Kanno, M., Hiramatsu, S., Kondo, S., Tanimoto, H., & Ichinose, T. (2021). Voluntary intake of psychoactive substances is regulated by the dopamine receptor Dop1R1 in Drosophila. Scientific Reports, 11(1), 3432. https://doi.org/10.1038/s41598-021-82813-0
Page 199 and 200. Rats preferred food.
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Page 200. And just like in humans.
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1397. Gage, S. H., & Sumnall, H. R. (2019). Rat Park: How a rat paradise changed the narrative of addiction. Addiction, 114(5), 917–922. https://doi.org/10.1111/add.14481
1398. Christie, N. C. (2021). The role of social isolation in opioid addiction. Social Cognitive and Affective Neuroscience, 16(7), 645–656. https://doi.org/10.1093/scan/nsab029
Page 200. This initial aversion. Sullivan et al. (2008) below coined the term “paradox of drug reward.”
1399. Sullivan, R. J., Hagen, E. H., & Hammerstein, P. (2008). Revealing the paradox of drug reward in human evolution. Proceedings of the Royal Society B: Biological Sciences, 275(1640), 1231–1241. https://doi.org/10.1098/rspb.2007.1673
Page 200. But when carpenter ants.
1400. Entler, B. v., Cannon, J. T., & Seid, M. A. (2016). Morphine addiction in ants: a new model for self-administration and neurochemical analysis. Journal of Experimental Biology, 219(18), 2865–2869. https://doi.org/10.1242/jeb.140616
Page 200. Another hint came.
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1404. Gavra, T., & Libersat, F. (2011). Involvement of the opioid system in the hypokinetic state induced in cockroaches by a parasitoid wasp. Journal of Comparative Physiology A, 197(3), 279–291. https://doi.org/10.1007/s00359-010-0610-9
Page 201. For monarch butterflies.
1405. Zalucki, M. P., Brower, L. P., & Alonso‐M, A. (2001). Detrimental effects of latex and cardiac glycosides on survival and growth of first‐instar monarch butterfly larvae Danaus plexippus feeding on the sandhill milkweed Asclepias humistrata. Ecological Entomology, 26(2), 212–224. https://doi.org/10.1046/j.1365-2311.2001.00313.x
Page 202. For humans.
1406. Maté, G. (2008). In the realm of hungry ghosts: Close encounters with addiction. Random House Digital, Inc.
Page 203. Drug use disorders.
1407. Sullivan, R. J., Hagen, E. H., & Hammerstein, P. (2008). Revealing the paradox of drug reward in human evolution. Proceedings of the Royal Society B: Biological Sciences, 275(1640), 1231–1241. https://doi.org/10.1098/rspb.2007.1673
1408. Hagen, E. H., Sullivan, R. J., Schmidt, R., Morris, G., Kempter, R., & Hammerstein, P. (2009). Ecology and neurobiology of toxin avoidance and the paradox of drug reward. Neuroscience, 160(1), 69–84. https://doi.org/10.1016/j.neuroscience.2009.01.077
Chapter 10. The Herbivore’s Dilemma
Page 203. Quote beginning with“Tell me what you…” is from Brillat-Savarin’s 1825 bookreferenced below.
1409. Brillat-Savarin, J. A. (2009). The Physiology of Taste: or Meditations on Transcendental Gastronomy; Introduction by Bill Buford. Everyman's Library.
Page 203. Our choices.
1410. Nabhan, G. P. (2013). Food, genes, and culture: eating right for your origins. Washington, DC: Island Press.
Page 203 and 204. Anthropologist Fatimah Jackson.
1411. Jackson, L. C., Oseguera, M., Medrano, S., & Kim, Y. L. (1988). Carbamylation of hemoglobin in vivo with chronic sublethal dietary cyanide: Implications for hemoglobin S. Biochemical Medicine and Metabolic Biology, 39(1), 64–68. https://doi.org/10.1016/0885-4505(88)90059-X
1412. Jackson, F. L. C. (1990). Two evolutionary models for the interactions of dietary organic cyanogens, hemoglobins, and falciparum malaria. American Journal of Human Biology, 2(5), 521–532. https://doi.org/10.1002/ajhb.1310020508
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1417. Hardin, J. A., & Jackson, F. L. (2009). Applications of natural products in the control of mosquito-transmitted diseases. African Journal of Biotechnology, 8(25).
1418. Jackson, F., & Mulla, S. (2020). In conversation with Fatimah Jackson: The life and career of an African American Muslim biological anthropologist. Feminist Anthropology, 1(2), 155-164.
1419. Niba, L. L., Bokanga, M. M., Jackson, F. L., Schlimme, D. S., & Li, B. W. (2002). Physicochemical Properties and Starch Granular Characteristics of Flour from Various Manihot Esculenta (Cassava) Genotypes. Journal of Food Science, 67(5), 1701–1705. https://doi.org/10.1111/j.1365-2621.2002.tb08709.x
Page 205. Sickle cell disease. These references apply to the next five paragraphs as well.
1421. Herrick, J. B.. (1910). Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Archives of Internal Medicine, VI(5), 517–521. https://doi.org/10.1001/archinte.1910.00050330050003
1422. Allison, A. C. (1954). Protection Afforded by Sickle-cell Trait Against Subtertian Malarial Infection. BMJ, 1(4857), 290–294. https://doi.org/10.1136/bmj.1.4857.290
1424. Aidoo, M., Terlouw, D. J., Kolczak, M. S., McElroy, P. D., ter Kuile, F. O., Kariuki, S., Nahlen, B. L., Lal, A. A., & Udhayakumar, V. (2002). Protective effects of the sickle cell gene against malaria morbidity and mortality. The Lancet, 359(9314), 1311–1312. https://doi.org/10.1016/S0140-6736(02)08273-9
1425. Allison, A. C. (2009). Genetic control of resistance to human malaria. Current Opinion in Immunology, 21(5), 499–505. https://doi.org/10.1016/j.coi.2009.04.001
1427. Elguero, E., Délicat-Loembet, L. M., Rougeron, V., Arnathau, C., Roche, B., Becquart, P., Gonzalez, J.-P., Nkoghe, D., Sica, L., Leroy, E. M., Durand, P., Ayala, F. J., Ollomo, B., Renaud, F., & Prugnolle, F. (2015). Malaria continues to select for sickle cell trait in Central Africa. Proceedings of the National Academy of Sciences, 112(22), 7051–7054. https://doi.org/10.1073/pnas.1505665112
1429. Teles, F. F. F. (2002). Chronic poisoning by hydrogen cyanide in cassava and its prevention in Africa and Latin America. Food and Nutrition Bulletin, 23(4), 407–412. https://doi.org/10.1177/156482650202300418
1430. Nzwalo, H., & Cliff, J. (2011). Konzo: From Poverty, Cassava, and Cyanogen Intake to Toxico-Nutritional Neurological Disease. PLoS Neglected Tropical Diseases, 5(6), e1051. https://doi.org/10.1371/journal.pntd.0001051
1431. Wang, W., Feng, B., Xiao, J., Xia, Z., Zhou, X., Li, P., Zhang, W., Wang, Y., Møller, B. L., Zhang, P., Luo, M.-C., Xiao, G., Liu, J., Yang, J., Chen, S., Rabinowicz, P. D., Chen, X., Zhang, H.-B., Ceballos, H., … Peng, M. (2014). Cassava genome from a wild ancestor to cultivated varieties. Nature Communications, 5(1), 5110. https://doi.org/10.1038/ncomms6110
1432. Pinto-Zevallos, D. M., Pareja, M., & Ambrogi, B. G. (2016). Current knowledge and future research perspectives on cassava (Manihot esculenta Crantz) chemical defenses: An agroecological view. Phytochemistry, 130, 10–21. https://doi.org/10.1016/j.phytochem.2016.05.013
1434. Iwuagwu, O. (2012). The spread of cassava (manioc) in Igboland, south-east Nigeria: a reappraisal of the evidence. The Agricultural History Review, 60(1), 60–76. http://www.jstor.org/stable/23317131
1435. Jackson, F. L. C., Jackson, R. T., Delumen, B. O., Sio, F. K., Dinkins, L., & Muhammad, A. F. H. (1992). Cassava ( Manihot esculent a) in Liberia: History, geography, traditional processing and cyanogenic glycoside levels. Ecology of Food and Nutrition, 28(3), 227–242. https://doi.org/10.1080/03670244.1992.9991274
Page 205. Fatiman Jackson found that.
1436. Jackson, F. L. C. (1990). Two evolutionary models for the interactions of dietary organic cyanogens, hemoglobins, and falciparum malaria. American Journal of Human Biology, 2(5), 521–532. https://doi.org/10.1002/ajhb.1310020508
Page 205. Two activities.
1437. Deykin, D., Balko, C., & Cerami, A. (1972). Cyanate as an Inhibitor of Red-Cell Sickling. New England Journal of Medicine, 287(16), 807–812. https://doi.org/10.1056/NEJM197210192871606
1438. de Furia, F. G., Miller, D. R., Cerami, A., & Manning, J. M. (1972). The Effects of Cyanate In Vitro on Red Blood Cell Metabolism and Function in Sickle Cell Anemia. Journal of Clinical Investigation, 51(3), 566–574. https://doi.org/10.1172/JCI106845
1439. May, A., Bellingham, A. J., Huehns, E. R., & Beaven, G. H. (1972). Effect of cyanate on sickling. The Lancet, 299(7752), 658–661. https://doi.org/10.1016/S0140-6736(72)90462-X
1440. Nagel, R. L., Raventos, C., Tanowitz, H. B., & Wittner, M. (1980). Effect of sodium cyanate on Plasmodium falciparum in vitro. The Journal of Parasitology, 66(3), 483–487.
1441. Jackson, L. C., Oseguera, M., Medrano, S., & Kim, Y. L. (1988). Carbamylation of hemoglobin in vivo with chronic sublethal dietary cyanide: Implications for hemoglobin S. Biochemical Medicine and Metabolic Biology, 39(1), 64–68. https://doi.org/10.1016/0885-4505(88)90059-X
1442. Jackson, F. L. C. (1990). Two evolutionary models for the interactions of dietary organic cyanogens, hemoglobins, and falciparum malaria. American Journal of Human Biology, 2(5), 521–532. https://doi.org/10.1002/ajhb.1310020508
Page 206. Putting two and two. This reference supports the next two paragraphs as well.
1443. Jackson, F. L. C. (1990). Two evolutionary models for the interactions of dietary organic cyanogens, hemoglobins, and falciparum malaria. American Journal of Human Biology, 2(5), 521–532. https://doi.org/10.1002/ajhb.1310020508
Page 206. Indeed, cyanates can cross. From Jackson (1990): “newborns in many high cyanogen consuming indigenous groups are ritually given small amounts of specific cassava-based foods as reaffirmations of their membership in that ethnic group or clan. Thus, an indigenous Liberian’s postnatal exposure to dietary cyanogens may begin very early.”
1444. Tewe, O. O., Maner, J. H., & Gomez, G. (1977). Influence of cassava diets on placental thiocyanate transfer, tissue rhodanese activity and performance of rats during gestation. Journal of the Science of Food and Agriculture, 28(8), 750–756. https://doi.org/10.1002/jsfa.2740280814
1445. Meberg, A., Sande, H., Foss, O. P., & Stenwig, J. T. (1979). Smoking during pregnancy—Effects on the fetus and on thiocyanate levels in mother and baby. Acta Paediatrica, 68(5), 547–552. https://doi.org/10.1111/j.1651-2227.1979.tb05053.x
1446. Dorea, J. G. (2004). Maternal Thiocyanate and Thyroid Status during Breast-Feeding. Journal of the American College of Nutrition, 23(2), 97–101. https://doi.org/10.1080/07315724.2004.10719348
Page 206 and 207.
1447. Cliff, J., Nicala, D., Saute, F., Givragy, R., Azambuja, G., Taela, A., Chavane, L., & Howarth, J. (1997). Konzo associated with war in Mozambique. Tropical Medicine and International Health, 2(11), 1068–1074. https://doi.org/10.1046/j.1365-3156.1997.d01-178.x
1448. Nzwalo, H., & Cliff, J. (2011). Konzo: From Poverty, Cassava, and Cyanogen Intake to Toxico-Nutritional Neurological Disease. PLoS Neglected Tropical Diseases, 5(6), e1051. https://doi.org/10.1371/journal.pntd.0001051
1450. Wilson, W. M., & Dufour, D. L. (2002). Why “bitter” cassava? Productivity of “bitter” and “sweet” cassava in a Tukanoan Indian settlement in the northwest Amazon. Economic Botany, 56(1), 49-57. http://www.jstor.org/stable/4256519
Page 208. Malaria was introduced. The date 1558 as the date for introduction of cassava is contentious and after the book had gone to press some new information came to light in a 2023 publication. According to many secondary sources (e.g., Silvestre and Arraudeau 1983), this is the date of its first appearance, attributed to the Portuguese, using Mauny’s reference to 1558. But according to Ankei, Mauny’s reference to 1558 had nothing to do with the introduction to Africa question and was referring to a report by Thevet in 1558 from Brazil, where it is native. As for the malaria question, this was addressed earlier in the discussion of the use of quinine. However, some nuance is important here too–Plasmodium falciparum unquestionably was moved via the Colombian exchange and trans-Atlantic slave trade from humans in Europe and Africa. However, several lines of evidence indicates the possibility that other Plasmodium species (e.g. P. vivax) may have already been in the “New World” prior to European colonization but there remains significant skepticism given shortcomings of the approaches used to address the question and the results of the Dorp et al. (2020) study referenced below, and the fact that no known malaria-resistance alleles are segregating in Indigenous South American individuals.
1451. Thevet, A. (1558). Les singularitez de la France Antarctique, autrement nommée Amérique: & de plusieurs terres et isles Découvertes de nostre temps. Maurice de La Porte.
1452. Mauny, R. (1953). Notes historiques autour des principales plantes cultivées d’Afrique occidentale. Bulletin d l’institut français d’afrique noire 15, 684–730.
1453. Yalcindag, E., Elguero, E., Arnathau, C., Durand, P., Akiana, J., Anderson, T. J., Aubouy, A., Balloux, F., Besnard, P., Bogreau, H., Carnevale, P., D’Alessandro, U., Fontenille, D., Gamboa, D., Jombart, T., le Mire, J., Leroy, E., Maestre, A., Mayxay, M., … Prugnolle, F. (2012). Multiple independent introductions of Plasmodium falciparum in South America. Proceedings of the National Academy of Sciences, 109(2), 511–516. https://doi.org/10.1073/pnas.1119058109
1454. Rodrigues, P. T., Valdivia, H. O., de Oliveira, T. C., Alves, J. M. P., Duarte, A. M. R. C., Cerutti-Junior, C., Buery, J. C., Brito, C. F. A., de Souza, J. C., Hirano, Z. M. B., Bueno, M. G., Catão-Dias, J. L., Malafronte, R. S., Ladeia-Andrade, S., Mita, T., Santamaria, A. M., Calzada, J. E., Tantular, I. S., Kawamoto, F., … Ferreira, M. U. (2018). Human migration and the spread of malaria parasites to the New World. Scientific Reports, 8(1), 1993. https://doi.org/10.1038/s41598-018-19554-0
1455. Loy, D. E., Plenderleith, L. J., Sundararaman, S. A., Liu, W., Gruszczyk, J., Chen, Y.-J., Trimboli, S., Learn, G. H., MacLean, O. A., Morgan, A. L. K., Li, Y., Avitto, A. N., Giles, J., Calvignac-Spencer, S., Sachse, A., Leendertz, F. H., Speede, S., Ayouba, A., Peeters, M., … Hahn, B. H. (2018). Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites. Proceedings of the National Academy of Sciences, 115(36). https://doi.org/10.1073/pnas.1810053115
1456. van Dorp, L., Gelabert, P., Rieux, A., de Manuel, M., de-Dios, T., Gopalakrishnan, S., Carøe, C., Sandoval-Velasco, M., Fregel, R., Olalde, I., Escosa, R., Aranda, C., Huijben, S., Mueller, I., Marquès-Bonet, T., Balloux, F., Gilbert, M. T. P., & Lalueza-Fox, C. (2020). Plasmodium vivax Malaria Viewed through the Lens of an Eradicated European Strain. Molecular Biology and Evolution, 37(3), 773–785. https://doi.org/10.1093/molbev/msz264
1457. Ankei, T. (2023). Diffusion of Cassava Detoxification in Africa: A Reconsideration of its Biocultural History. African Study Monographs. Supplementary Issue., 61, 93-138. https://doi.org/10.14989/282792 See page 95.
Page 208. Under this idea.
1458. Dunn, F. L. (1965). On the antiquity of malaria in the western hemisphere. Human Biology, 37(4) 385-393. http://www.jstor.org/stable/41448749
Page 208. Jackon’s idea is that. Gene-culture coevolution is the framing of this statement.
1460. Cavalli-Sforza, L. L., & Feldman, M. W. (1981). Cultural transmission and evolution: A quantitative approach (No. 16). Princeton University Press.
1461. Etkin, N. L. (2003). The co-evolution of people, plants, and parasites: biological and cultural adaptations to malaria. Proceedings of the Nutrition Society, 62(2), 311–317. https://doi.org/10.1079/pns2003244
1462. Nabhan, G. P. (2013). Finding a Bean for Your Genes and a Buffer Against Malaria. In Food, Genes, and Culture (pp. 63–91). Island Press/Center for Resource Economics. https://doi.org/10.5822/978-1-61091-493-2_4
Page 208. Like so many.
1463. Weld, E. D., Waitt, C., Barnes, K., & Garcia Bournissen, F. (2022). Twice neglected? Neglected diseases in neglected populations. British Journal of Clinical Pharmacology, 88(2), 367–373. https://doi.org/10.1111/bcp.15148
Page 209. The bacteria living.
1464. Beijerinck, M. W. (1901). Uber oligonitrophile mikroben. Zentralbl. Bakterol. Parasitenkd. Infektionskr. Hyg. Abt. II., 7, 561-582.
1465. Multari, S., Stewart, D., & Russell, W. R. (2015). Potential of Fava Bean as Future Protein Supply to Partially Replace Meat Intake in the Human Diet. Comprehensive Reviews in Food Science and Food Safety, 14(5), 511–522. https://doi.org/10.1111/1541-4337.12146
Page 209. I can see why. Note that fava, faba, and broad bean all refer to Vicia faba.
1468. Jayakodi, M., Golicz, A. A., Kreplak, J., Fechete, L. I., Angra, D., Bednář, P., Bornhofen, E., Zhang, H., Boussageon, R., Kaur, S., Cheung, K., Čížková, J., Gundlach, H., Hallab, A., Imbert, B., Keeble-Gagnère, G., Koblížková, A., Kobrlová, L., Krejčí, P., … Andersen, S. U. (2023). The giant diploid faba genome unlocks variation in a global protein crop. Nature, 615(7953), 652–659. https://doi.org/10.1038/s41586-023-05791-5
Page 209. Luckily, neither Shane.
1469. Carson, P. E., Flanagan, C. L., Ickes, C. E., & Alving, A. S. (1956). Enzymatic Deficiency in Primaquine-Sensitive Erythrocytes. Science, 124(3220), 484–485. https://doi.org/10.1126/science.124.3220.484.b
Page 210. Intriguingly.
1470. Hutton, J. E. (1937). Favism: an unusually observed type of hemolytic anemia. Journal of the American Medical Association, 109(20), 1618-1620. https://doi.org/10.1001/jama.1937.02780460028007
1471. ALLISON, A. C. (1960). Glucose-6-Phosphate Dehydrogenase Deficiency in Red Blood Cells of East Africans. Nature, 186(4724), 531–532. https://doi.org/10.1038/186531a0
1472. Motulsky, A. (1961). Glucose-6-phosphate-dehydrogenase deficiency, haemolytic disease of the newborn, and malaria. The Lancet, 277(7187), 1168-1169. https://doi.org/10.1016/S0140-6736(61)92095-5
1473. Roth, E. F., Raventos-Suarez, C., Rinaldi, A., & Nagel, R. L. (1983). Glucose-6-phosphate dehydrogenase deficiency inhibits in vitro growth of Plasmodium falciparum. Proceedings of the National Academy of Sciences, 80(1), 298–299. https://doi.org/10.1073/pnas.80.1.298
1474. Tishkoff, S. A., Varkonyi, R., Cahinhinan, N., Abbes, S., Argyropoulos, G., Destro-Bisol, G., Drousiotou, A., Dangerfield, B., Lefranc, G., Loiselet, J., Piro, A., Stoneking, M., Tagarelli, A., Tagarelli, G., Touma, E. H., Williams, S. M., & Clark, A. G. (2001). Haplotype Diversity and Linkage Disequilibrium at Human G6PD : Recent Origin of Alleles That Confer Malarial Resistance. Science, 293(5529), 455–462. https://doi.org/10.1126/science.1061573
Page 211. One theory is that people.
1475. Huheey, J. E., & Martin, D. L. (1975). Malaria, favism and glucose-6-phosphate dehydrogenase deficiency. Experientia, 31(10), 1145-1147. https://doi.org/10.1007/bf02326760
1476. Golenser, J., Miller, J., Spira, D., Navok, T., & Chevion, M. (1983). Inhibitory effect of a fava bean component on the in vitro development of Plasmodium falciparum in normal and glucose-6-phosphate dehydrogenase deficient erythrocytes. Blood, 61(3), 507–510. https://doi.org/10.1182/blood.V61.3.507.507
1477. Clark, I. A., Cowden, W. B., Hunt, N. H., Maxwell, L. E., & Mackie, E. J. (1984). Activity of divicine in Plasmodium vinckei-infected mice has implications for treatment of favism and epidemiology of G-6-PD deficiency. British Journal of Haematology, 57(3), 479–487. https://doi.org/10.1111/j.1365-2141.1984.tb02922.x
1479. Ginsburg, H., Atamna, H., Shalmiev, G., Kanaani, J., & Krugliak, M. (1996). Resistance of glucose-6-phosphate dehydrogenase deficiency to malaria: effects of fava bean hydroxypyrimidine glucosides on Plasmodium falciparum growth in culture and on the phagocytosis of infected cells. Parasitology, 113(1), 7–18. https://doi.org/10.1017/S0031182000066221
1481. Sallares, R., Bouwman, A., & Anderung, C. (2004). The Spread of Malaria to Southern Europe in Antiquity: New Approaches to Old Problems. Medical History, 48(3), 311–328. https://doi.org/10.1017/S0025727300007651
Page 211. In book 8.
1482. Arie, T. H. D. (1961). Pythagoras and the Beans. British Medical Journal, 2(5253), 709.
1483. Moynahan, E. J. (1961). Pythagoras and the Beans. British Medical Journal, 2(5256), 897.
1484. Scarborough, J. (1982). Beans, Pythagoras, Taboos, and Ancient Dietetics. The Classical World, 75(6), 355. https://doi.org/10.2307/4349404
1485. Hatfield, G. (2000). Plants of Life, Plants of Death. Folklore, 111(2), 317-317.
1486. Meletis, J., & Konstantopoulos, K. (2004). Favism-from the “avoid fava beans” of Pythagoras to the present. Haema, 7(1), 17-21.
1487. Laertius, D. (2020). Lives of the Eminent Philosophers: Compact Edition. Oxford University Press.
1489. Wharton, H. J., & Duesselmann, W. (1947). Favism: A short review and report of a case. New England Journal of Medicine, 236(26), 974–977. https://doi.org/10.1056/NEJM194706262362604
1490. Belsey, M. A. (1973). The epidemiology of favism. Bulletin of the World Health Organization, 48(1), 1–13.
1492. Belsey, M. A. (1973). The epidemiology of favism. Bulletin of the World Health Organization, 48(1), 1–13.
1493. Kaplan, M., Vreman, H. J., Hammerman, C., Schimmel, M. S., Abrahamov, A., & Stevenson, D. K. (1998). Favism by proxy in nursing glucose-6-phosphate dehydrogenase-deficient neonates. Journal of Perinatology: Official Journal of the California Perinatal Association, 18(6 Pt 1), 477-479.
Page 212. The bitterness came from the.
1494. de Keukeleire, J., Ooms, G., Heyerick, A., Roldan-Ruiz, I., van Bockstaele, E., & de Keukeleire, D. (2003). Formation and Accumulation of α-Acids, β-Acids, Desmethylxanthohumol, and Xanthohumol during Flowering of Hops ( Humulus lupulus L.). Journal of Agricultural and Food Chemistry, 51(15), 4436–4441. https://doi.org/10.1021/jf034263z
Page 212. Hops from the hop plant.
1495. DeLyser, D. Y., & Kasper, W. J. (1994). Hopped Beer: The Case for Cultivation. Economic Botany, 48(2), 166–170. http://www.jstor.org/stable/4255609
1496. Moir, M. (2000). Hops—A Millennium Review. Journal of the American Society of Brewing Chemists, 58(4), 131–146. https://doi.org/10.1094/ASBCJ-58-0131
1497. Sakamoto, K., & Konings, W. N. (2003). Beer spoilage bacteria and hop resistance. International Journal of Food Microbiology, 89(2–3), 105–124. https://doi.org/10.1016/S0168-1605(03)00153-3
1498. Patterson, M. W., & Hoalst-Pullen, N. (2014). Geographies of beer. In The geography of beer: Regions, environment, and societies (pp. 1-5). Dordrecht: Springer Netherlands. https://doi.org/10.1007/978-94-007-7787-3
Page 212. Science demands a more general.
1499. Sullivan, R. J., Hagen, E. H., & Hammerstein, P. (2008). Revealing the paradox of drug reward in human evolution. Proceedings of the Royal Society B: Biological Sciences, 275(1640), 1231–1241. https://doi.org/10.1098/rspb.2007.1673
1500. Hagen, E. H., Sullivan, R. J., Schmidt, R., Morris, G., Kempter, R., & Hammerstein, P. (2009). Ecology and neurobiology of toxin avoidance and the paradox of drug reward. Neuroscience, 160(1), 69–84. https://doi.org/10.1016/j.neuroscience.2009.01.077
Page 213. A backup system.
1501. Borison, H. L., Borison, R., & McCarthy, L. E. (1984). Role of the area postrema in vomiting and related functions. Federation Proceedings, 43(15), 2955–2958.
1502. Glendinning, J. I. (2007). How Do Predators Cope With Chemically Defended Foods? The Biological Bulletin, 213(3), 252–266. https://doi.org/10.2307/25066643
1505. Logue, A. W., Ophir, I., & Strauss, K. E. (1981). The acquisition of taste aversions in humans. Behaviour Research and Therapy, 19(4), 319–333. https://doi.org/10.1016/0005-7967(81)90053-X
Page 214 and 215. Physiologist John Glendinning. These references support the next six paragraphs as well.
1507. Freeland, W. J., & Janzen, D. H. (1974). Strategies in Herbivory by Mammals: The Role of Plant Secondary Compounds. The American Naturalist, 108(961), 269–289. https://doi.org/10.1086/282907
1509. Jermy, T., Bernays, E. A., & Szentesi, A. (1982). The effect of repeated exposure to feeding deterrents on their acceptability to phytophagous insects. In 5th International Symposium on Insect-Plant Relationships (ed. by JH Visser & AK Minks) (pp. 25-32).
1510. Skopec, M. M., Hagerman, A. E., & Karasov, W. H. (2004). Do Salivary Proline-Rich Proteins Counteract Dietary Hydrolyzable Tannin in Laboratory Rats? Journal of Chemical Ecology, 30(9), 1679–1692. https://doi.org/10.1023/B:JOEC.0000042395.31307.be
Page 216. And like oak gall wasps.
1511. Athanasiadou, S., Kyriazakis, I., Jackson, F., & Coop, R. L. (2000). Effects of short-term exposure to condensed tannins on adult Trichostrongylus colubriformis. Veterinary Record, 146(25), 728–732. https://doi.org/10.1136/vr.146.25.728
1512. Athanasiadou, S., Kyriazakis, I., Jackson, F., & Coop, R. L. (2001). Direct anthelmintic effects of condensed tannins towards different gastrointestinal nematodes of sheep: in vitro and in vivo studies. Veterinary Parasitology, 99(3), 205–219. https://doi.org/10.1016/S0304-4017(01)00467-8
1513. Lisonbee, L. D., Villalba, J. J., Provenza, F. D., & Hall, J. O. (2009). Tannins and self-medication: Implications for sustainable parasite control in herbivores. Behavioural Processes, 82(2), 184–189. https://doi.org/10.1016/j.beproc.2009.06.009
Page 216. Carnivores tend to have.
1514. Kim, S., Cho, Y. S., Kim, H.-M., Chung, O., Kim, H., Jho, S., Seomun, H., Kim, J., Bang, W. Y., Kim, C., An, J., Bae, C. H., Bhak, Y., Jeon, S., Yoon, H., Kim, Y., Jun, J., Lee, H., Cho, S., … Yeo, J.-H. (2016). Comparison of carnivore, omnivore, and herbivore mammalian genomes with a new leopard assembly. Genome Biology, 17(1), 211. https://doi.org/10.1186/s13059-016-1071-4
1515. Hecker, N., Sharma, V., & Hiller, M. (2019). Convergent gene losses illuminate metabolic and physiological changes in herbivores and carnivores. Proceedings of the National Academy of Sciences, 116(8), 3036–3041. https://doi.org/10.1073/pnas.1818504116
1518. Wegenast, C. A., Meadows, I. D., Anderson, R. E., Southard, T., González Barrientos, C. R., & Wismer, T. A. (2022). Acute kidney injury in dogs following ingestion of cream of tartar and tamarinds and the connection to tartaric acid as the proposed toxic principle in grapes and raisins. Journal of Veterinary Emergency and Critical Care, 32(6), 812–816. https://doi.org/10.1111/vec.13234
Page 217. Another well-known.
1519. Gruhzit, O. M. (1931). Anemia in dogs produced by feeding disulphide compounds. Am. J. Med. Sci., 181, 815-820.
1520. Hill, A. S., O’Neill, S., Rogers, Q. R., & Christopher, M. M. (2001). Antioxidant prevention of Heinz body formation and oxidative injury in cats. American Journal of Veterinary Research, 62(3), 370–374. https://doi.org/10.2460/ajvr.2001.62.370
1521. Tang, X., Xia, Z., & Yu, J. (2008). An experimental study of hemolysis induced by onion ( Allium cepa ) poisoning in dogs. Journal of Veterinary Pharmacology and Therapeutics, 31(2), 143–149. https://doi.org/10.1111/j.1365-2885.2007.00930.x
Page 217. Few children.
1522. Repacholi, B. M., & Gopnik, A. (1997). Early reasoning about desires: Evidence from 14- and 18-month-olds. Developmental Psychology, 33(1), 12–21. https://doi.org/10.1037/0012-1649.33.1.12
1523. Mennella, J. A., Pepino, M. Y., & Reed, D. R. (2005). Genetic and Environmental Determinants of Bitter Perception and Sweet Preferences. Pediatrics, 115(2), e216–e222. https://doi.org/10.1542/peds.2004-1582
1524. Bell, K. I., & Tepper, B. J. (2006). Short-term vegetable intake by young children classified by 6- n-propylthoiuracil bitter-taste phenotypey. The American Journal of Clinical Nutrition, 84(1), 245–251. https://doi.org/10.1093/ajcn/84.1.245
Page 217. Omnivorous dogs like to eat.
1525. Bradshaw, J. W. S. (2006). The Evolutionary Basis for the Feeding Behavior of Domestic Dogs (Canis familiaris) and Cats (Felis catus). The Journal of Nutrition, 136(7), 1927S-1931S. https://doi.org/10.1093/jn/136.7.1927S
1526. Bosch, G., Hagen-Plantinga, E. A., & Hendriks, W. H. (2015). Dietary nutrient profiles of wild wolves: insights for optimal dog nutrition? British Journal of Nutrition, 113(S1), S40–S54. https://doi.org/10.1017/S0007114514002311
Page 217. Wolves in Minnesota.
1527. Gable, T. D., Windels, S. K., & Bruggink, J. G. (2017). Estimating Biomass of Berries Consumed by Gray Wolves. Wildlife Society Bulletin, 41(1), 129–131. https://www.jstor.org/stable/90003996
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Page 217 and 218. As they began.
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Page 220. More important for the purposes of this book.
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Page 220. Even though they are smaller.
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1564. Goyal, M. S., & Raichle, M. E. (2018). Glucose Requirements of the Developing Human Brain. Journal of Pediatric Gastroenterology & Nutrition, 66(3), S46–S49. https://doi.org/10.1097/MPG.0000000000001875
Page 220. Although people show much variation.
1565. Thompson, D. A., Moskowitz, H. R., & Campbell, R. G. (1976). Effects of body weight and food intake on pleasantness ratings for a sweet stimulus. Journal of Applied Physiology, 41(1), 77–83. https://doi.org/10.1152/jappl.1976.41.1.77
1566. Braun, T. D., Kunicki, Z. J., Blevins, C. E., Stein, M. D., Marsh, E., Feltus, S., Miranda, R., Thomas, J. G., & Abrantes, A. M. (2021). Prospective Associations between Attitudes toward Sweet Foods, Sugar Consumption, and Cravings for Alcohol and Sweets in Early Recovery from Alcohol Use Disorders. Alcoholism Treatment Quarterly, 39(3), 269–281. https://doi.org/10.1080/07347324.2020.1868958
Page 221. An underactive. This reference applies to the next paragraph as well.
1567. Garbutt, J. C., Kampov-Polevoy, A. B., Kalka-Juhl, L. S., & Gallop, R. J. (2016). Association of the Sweet-Liking Phenotype and Craving for Alcohol With the Response to Naltrexone Treatment in Alcohol Dependence. JAMA Psychiatry, 73(10), 1056. https://doi.org/10.1001/jamapsychiatry.2016.2157
1568. Bouhlal, S., Farokhnia, M., Lee, M. R., Akhlaghi, F., & Leggio, L. (2018). Identifying and Characterizing Subpopulations of Heavy Alcohol Drinkers Via a Sucrose Preference Test: A Sweet Road to a Better Phenotypic Characterization? Alcohol and Alcoholism, 53(5), 560–569. https://doi.org/10.1093/alcalc/agy048
1569. Iatridi, V., Hayes, J. E., & Yeomans, M. R. (2019). Reconsidering the classification of sweet taste liker phenotypes: A methodological review. Food Quality and Preference, 72, 56–76. https://doi.org/10.1016/j.foodqual.2018.09.001
1570. Braun, T. D., Kunicki, Z. J., Blevins, C. E., Stein, M. D., Marsh, E., Feltus, S., Miranda, R., Thomas, J. G., & Abrantes, A. M. (2021). Prospective Associations between Attitudes toward Sweet Foods, Sugar Consumption, and Cravings for Alcohol and Sweets in Early Recovery from Alcohol Use Disorders. Alcoholism Treatment Quarterly, 39(3), 269–281. https://doi.org/10.1080/07347324.2020.1868958
Page 222. In search of glucose. The preferences or lack thereof for raw vs. cooked vegetables is highly nuanced. For example, in one study there was no significant difference between raw carrots vs. carrots that were boiled or oven-baked, there was a significant preference for raw tomatoes vs. cooked tomatoes, and there was a preference for cooked spinach over raw spinach (Donadini et al. 2012).
1571. Lawless, H. (1985). Sensory development in children: Research in taste and olfaction. Journal of the American Dietetic Association, 85(5), 577–583. https://doi.org/10.1016/S0002-8223(21)03656-7
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1573. Baxter, I. A., & Schroder, M. J. A. (1997). Vegetable consumption among Scottish children: a review of the determinants and proposed strategies to overcome low consumption. British Food Journal, 99(10), 380–387. https://doi.org/10.1108/00070709710195167
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1576. Donadini, G., Fumi, M. D., & Porretta, S. (2012). Influence of preparation method on the hedonic response of preschoolers to raw, boiled or oven-baked vegetables. LWT - Food Science and Technology, 49(2), 282–292. https://doi.org/10.1016/j.lwt.2012.07.019
1577. Poelman, A. A. M., Delahunty, C. M., & de Graaf, C. (2013). Cooking time but not cooking method affects children’s acceptance of Brassica vegetables. Food Quality and Preference, 28(2), 441–448. https://doi.org/10.1016/j.foodqual.2012.12.003
Page 222. Like most other people.
1578. Bell, K. I., & Tepper, B. J. (2006). Short-term vegetable intake by young children classified by 6- n-propylthoiuracil bitter-taste phenotypey. The American Journal of Clinical Nutrition, 84(1), 245–251. https://doi.org/10.1093/ajcn/84.1.245
1579. Anzman-Frasca, S., Savage, J. S., Marini, M. E., Fisher, J. O., & Birch, L. L. (2012). Repeated exposure and associative conditioning promote preschool children’s liking of vegetables. Appetite, 58(2), 543–553. https://doi.org/10.1016/j.appet.2011.11.012
1580. Dominguez, P. R. (2013). Development and Acquisition of Flavor and Food Preferences in Children: An Update Until 2010. Journal of Food Research, 3(1), 1. https://doi.org/10.5539/jfr.v3n1p1
Page 222 and 223. Anthropologists Edward Hagen. These references apply to the next five paragraphs as well. Note that the data cited by Hagen et al. (2013) are from: Centers for Disease Control and Prevention (CDC). National Center for Health Statistics (NCHS). National Health and Nutrition Examination Survey Data. Hyattsville, MD: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention (1999-2010).
1583. Sullivan, R. J., Hagen, E. H., & Hammerstein, P. (2008). Revealing the paradox of drug reward in human evolution. Proceedings of the Royal Society B: Biological Sciences, 275(1640), 1231–1241. https://doi.org/10.1098/rspb.2007.1673
1584. Degenhardt, L., Chiu, W.-T., Sampson, N., Kessler, R. C., Anthony, J. C., Angermeyer, M., Bruffaerts, R., de Girolamo, G., Gureje, O., Huang, Y., Karam, A., Kostyuchenko, S., Lepine, J. P., Mora, M. E. M., Neumark, Y., Ormel, J. H., Pinto-Meza, A., Posada-Villa, J., Stein, D. J., … Wells, J. E. (2008). Toward a Global View of Alcohol, Tobacco, Cannabis, and Cocaine Use: Findings from the WHO World Mental Health Surveys. PLoS Medicine, 5(7), e141. https://doi.org/10.1371/journal.pmed.0050141
1585. Hagen, E. H., Roulette, C. J., & Sullivan, R. J. (2013). Explaining Human Recreational Use of ‘pesticides’: The Neurotoxin Regulation Model of Substance Use vs. the Hijack Model and Implications for Age and Sex Differences in Drug Consumption. Frontiers in Psychiatry, 4. https://doi.org/10.3389/fpsyt.2013.00142
1586. Hagen, E. H., & Tushingham, S. (2019). The prehistory of psychoactive drug use. In Handbook of cognitive archaeology (pp. 471-498). Routledge.
1587. Hagen, E. H., Blackwell, A. D., Lightner, A. D., & Sullivan, R. J. (2023). Homo medicus : The transition to meat eating increased pathogen pressure and the use of pharmacological plants in Homo. American Journal of Biological Anthropology, 180(4), 589–617. https://doi.org/10.1002/ajpa.24718
Page 223. Yet there is virtually no coffee.
1588. Knight, C. A., Knight, I., Mitchell, D. C., & Zepp, J. E. (2004). Beverage caffeine intake in US consumers and subpopulations of interest: estimates from the Share of Intake Panel survey. Food and Chemical Toxicology, 42(12), 1923–1930. https://doi.org/10.1016/j.fct.2004.05.002
Page 223. The best explanation.
1589. Lawless, H. (1985). Sensory development in children: Research in taste and olfaction. Journal of the American Dietetic Association, 85(5), 577–583. https://doi.org/10.1016/S0002-8223(21)03656-7
1590. Bartoshuk, L. M., Duffy, V. B., & Miller, I. J. (1994). PTC/PROP tasting: Anatomy, psychophysics, and sex effects. Physiology & Behavior, 56(6), 1165–1171. https://doi.org/10.1016/0031-9384(94)90361-1
1591. Prutkin, J., Duffy, V. B., Etter, L., Fast, K., Gardner, E., Lucchina, L. A., Snyder, D. J., Tie, K., Weiffenbach, J., & Bartoshuk, L. M. (2000). Genetic variation and inferences about perceived taste intensity in mice and men. Physiology & Behavior, 69(1–2), 161–173. https://doi.org/10.1016/S0031-9384(00)00199-2
1592. Segovia, C., Hutchinson, I., Laing, D. G., & Jinks, A. L. (2002). A quantitative study of fungiform papillae and taste pore density in adults and children. Developmental Brain Research, 138(2), 135–146. https://doi.org/10.1016/S0165-3806(02)00463-7
1593. Wardle, J., & Cooke, L. (2008). Genetic and environmental determinants of children’s food preferences. British Journal of Nutrition, 99(S1), S15–S21. https://doi.org/10.1017/S000711450889246X
1594. Dovey, T. M., Staples, P. A., Gibson, E. L., & Halford, J. C. G. (2008). Food neophobia and ‘picky/fussy’ eating in children: A review. Appetite, 50(2–3), 181–193. https://doi.org/10.1016/j.appet.2007.09.009
1595. Mennella, J. A., & Bobowski, N. K. (2015). The sweetness and bitterness of childhood: Insights from basic research on taste preferences. Physiology & Behavior, 152, 502–507. https://doi.org/10.1016/j.physbeh.2015.05.015
1596. Hoffman, A. C., Salgado, R. V., Dresler, C., Faller, R. W., & Bartlett, C. (2016). Flavour preferences in youth versus adults: a review. Tobacco Control, 25(Suppl 2), ii32–ii39. https://doi.org/10.1136/tobaccocontrol-2016-053192
Page 224. Intriguingly, researchers have also found.
1597. Bartoshuk, L. M., Duffy, V. B., & Miller, I. J. (1994). PTC/PROP tasting: Anatomy, psychophysics, and sex effects. Physiology & Behavior, 56(6), 1165–1171. https://doi.org/10.1016/0031-9384(94)90361-1
Page 224. The vast majority.
1598. Hook, E. (1978). Dietary cravings and aversions during pregnancy. The American Journal of Clinical Nutrition, 31(8), 1355–1362. https://doi.org/10.1093/ajcn/31.8.1355
1599. Profet, M. (1992). Pregnancy sickness as adaptation: A deterrent to maternal ingestion of teratogens. In J. H. Barkow, L. Cosmides, & J. Tooby (Eds.), The adapted mind: Evolutionary psychology and the generation of culture (pp. 327–365). Oxford University Press.
1600. Kölble, N., Hummel, T., von Mering, R., Huch, A., & Huch, R. (2001). Gustatory and olfactory function in the first trimester of pregnancy. European Journal of Obstetrics & Gynecology and Reproductive Biology, 99(2), 179–183. https://doi.org/10.1016/S0301-2115(01)00408-0
1601. Nordin, S., Broman, D. A., Olofsson, J. K., & Wulff, M. (2004). A longitudinal descriptive study of self-reported abnormal smell and taste perception in pregnant women. Chemical Senses, 29(5), 391–402. https://doi.org/10.1093/chemse/bjh040
1602. Lawson, C. C., LeMasters, G. K., & Wilson, K. A. (2004). Changes in caffeine consumption as a signal of pregnancy. Reproductive Toxicology, 18(5), 625–633. https://doi.org/10.1016/j.reprotox.2004.03.004
1603. Pepper, G. v, & Craig Roberts, S. (2006). Rates of nausea and vomiting in pregnancy and dietary characteristics across populations. Proceedings of the Royal Society B: Biological Sciences, 273(1601), 2675–2679. https://doi.org/10.1098/rspb.2006.3633
1604. Patil, C. L., Abrams, E. T., Steinmetz, A. R., & Young, S. L. (2012). Appetite Sensations and Nausea and Vomiting in Pregnancy: An Overview of the Explanations. Ecology of Food and Nutrition, 51(5), 394–417. https://doi.org/10.1080/03670244.2012.696010
1605. Hagen, E. H., Roulette, C. J., & Sullivan, R. J. (2013). Explaining Human Recreational Use of ‘pesticides’: The Neurotoxin Regulation Model of Substance Use vs. the Hijack Model and Implications for Age and Sex Differences in Drug Consumption. Frontiers in Psychiatry, 4. https://doi.org/10.3389/fpsyt.2013.00142
1606. Isoherranen, N., & Thummel, K. E. (2013). Drug Metabolism and Transport During Pregnancy: How Does Drug Disposition Change during Pregnancy and What Are the Mechanisms that Cause Such Changes? Drug Metabolism and Disposition, 41(2), 256–262. https://doi.org/10.1124/dmd.112.050245
Page 224. For example.
1607. James, J. E. (2021). Maternal caffeine consumption and pregnancy outcomes: a narrative review with implications for advice to mothers and mothers-to-be. BMJ Evidence-Based Medicine, 26(3), 114–115. https://doi.org/10.1136/bmjebm-2020-111432
Page 224. Thalidomide. As discussed in Hagen et al. (2013).
1608. von Moos, R., Stolz, R., Cerny, T., & Gillessen, S. (2003). Thalidomide: from tragedy to promise. Swiss Medical Weekly, 133(5–6), 77–87. https://doi.org/10.4414/smw.2003.09947
1609. Hagen, E. H., Roulette, C. J., & Sullivan, R. J. (2013). Explaining Human Recreational Use of ‘pesticides’: The Neurotoxin Regulation Model of Substance Use vs. the Hijack Model and Implications for Age and Sex Differences in Drug Consumption. Frontiers in Psychiatry, 4. https://doi.org/10.3389/fpsyt.2013.00142
Page 224 and 224. Ethanol, nicotine.
1610. Ozturk, F., Sheldon, E., Sharma, J., Canturk, K. M., Otu, H. H., & Nawshad, A. (2016). Nicotine Exposure During Pregnancy Results in Persistent Midline Epithelial Seam With Improper Palatal Fusion. Nicotine & Tobacco Research, 18(5), 604–612. https://doi.org/10.1093/ntr/ntv227
1611. Hoyme, H. E., Kalberg, W. O., Elliott, A. J., Blankenship, J., Buckley, D., Marais, A.-S., Manning, M. A., Robinson, L. K., Adam, M. P., Abdul-Rahman, O., Jewett, T., Coles, C. D., Chambers, C., Jones, K. L., Adnams, C. M., Shah, P. E., Riley, E. P., Charness, M. E., Warren, K. R., & May, P. A. (2016). Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders. Pediatrics, 138(2). https://doi.org/10.1542/peds.2015-4256
1612. McGrath-Morrow, S. A., Gorzkowski, J., Groner, J. A., Rule, A. M., Wilson, K., Tanski, S. E., Collaco, J. M., & Klein, J. D. (2020). The Effects of Nicotine on Development. Pediatrics, 145(3). https://doi.org/10.1542/peds.2019-1346
Page 225. Hagen and collaborators.
1613. Hagen, E. H., Roulette, C. J., & Sullivan, R. J. (2013). Explaining Human Recreational Use of ‘pesticides’: The Neurotoxin Regulation Model of Substance Use vs. the Hijack Model and Implications for Age and Sex Differences in Drug Consumption. Frontiers in Psychiatry, 4. https://doi.org/10.3389/fpsyt.2013.00142
Page 226. The paradox of drug reward.
1614. Sullivan, R. J., Hagen, E. H., & Hammerstein, P. (2008). Revealing the paradox of drug reward in human evolution. Proceedings of the Royal Society B: Biological Sciences, 275(1640), 1231–1241. https://doi.org/10.1098/rspb.2007.1673
1616. Barretto-Tesoro, G. (2003). Burial goods in the Philippines: an attempt to quantify prestige values. Japanese Journal of Southeast Asian Studies, 41(3), 299-315.
1617. Zumbroich, T. J. (2008). The origin and diffusion of betel chewing: a synthesis of evidence from South Asia, Southeast Asia and beyond. E-Journal of Indian Medicine, 1(3), 87.
1618. Volgin, A. D., Bashirzade, A., Amstislavskaya, T. G., Yakovlev, O. A., Demin, K. A., Ho, Y.-J., Wang, D., Shevyrin, V. A., Yan, D., Tang, Z., Wang, J., Wang, M., Alpyshov, E. T., Serikuly, N., Wappler-Guzzetta, E. A., Lakstygal, A. M., & Kalueff, A. v. (2019). DARK Classics in Chemical Neuroscience: Arecoline. ACS Chemical Neuroscience, 10(5), 2176–2185. https://doi.org/10.1021/acschemneuro.8b00711
Page 227. The oldest bona fide.
1619. Fox, R. B. (1970). The Tabon caves: archaeological explorations and excavations on Palawan island, Philippines. National Museum, Manila.
1620. Barretto-Tesoro, G. (2003). Burial goods in the Philippines: an attempt to quantify prestige values. Japanese Journal of Southeast Asian Studies, 41(3), 299-315.
Page 227. All of the new terms.
1621. Palumbo, M. J., Talcott, S. T., & Putz, F. E. (2009). Ilex Vomitoria Ait. (Yaupon): A Native North American Source of a Caffeinated and Antioxidant-Rich Tea. Economic Botany, 63(2), 130–137. https://doi.org/10.1007/s12231-009-9078-3
1622. Schimpl, F. C., da Silva, J. F., Gonçalves, J. F. de C., & Mazzafera, P. (2013). Guarana: Revisiting a highly caffeinated plant from the Amazon. Journal of Ethnopharmacology, 150(1), 14–31. https://doi.org/10.1016/j.jep.2013.08.023
1623. Dueñas, J. F., Jarrett, C., Cummins, I., & Logan–Hines, E. (2016). Amazonian Guayusa (Ilex guayusa Loes.): A Historical and Ethnobotanical Overview. Economic Botany, 70(1), 85–91. https://doi.org/10.1007/s12231-016-9334-2
Page 228 and 229. Ethnobotanists Eloy Rodriguez.
1624. Rodriguez, E., Cavin, J. C., & West, J. E. (1982). The possible role of amazonian psychoactive plants in the chemotherapy of parasitic worms — a hypothesis. Journal of Ethnopharmacology, 6(3), 303–309. https://doi.org/10.1016/0378-8741(82)90053-8
1626. Luna, L. E. (1984). The concept of plants as teachers among four mestizo shamans of iquitos, Northeastern Peru. Journal of Ethnopharmacology, 11(2), 135–156. https://doi.org/10.1016/0378-8741(84)90036-9
Page 229. At least some of the chemicals.
1627. Cavin, J. C., Krassner, S. M., & Rodriguez, E. (1987). Plant-derived alkaloids active against Trypanosoma cruzi. Journal of Ethnopharmacology, 19(1), 89–94. https://doi.org/10.1016/0378-8741(87)90140-1
Page 230. Researchers in one study.
1628. Roulette, C. J., Kazanji, M., Breurec, S., & Hagen, E. H. (2016). High prevalence of cannabis use among Aka foragers of the Congo Basin and its possible relationship to helminthiasis. American Journal of Human Biology, 28(1), 5–15. https://doi.org/10.1002/ajhb.22740
1630. Hendriks, K. P., Kiefer, C., Al-Shehbaz, I. A., Bailey, C. D., Hooft van Huysduynen, A., Nikolov, L. A., Nauheimer, L., Zuntini, A. R., German, D. A., Franzke, A., Koch, M. A., Lysak, M. A., Toro-Núñez, Ó., Özüdoğru, B., Invernón, V. R., Walden, N., Maurin, O., Hay, N. M., Shushkov, P., … Lens, F. (2023). Global Brassicaceae phylogeny based on filtering of 1,000-gene dataset. Current Biology, 33(19), 4052-4068.e6. https://doi.org/10.1016/j.cub.2023.08.026
1631. Warwick, S. I. (2011). Brassicaceae in Agriculture. In Genetics and Genomics of the Brassicaceae (pp. 33–65). Springer New York. https://doi.org/10.1007/978-1-4419-7118-0_2
1632. Lysak, M. A. (2018). Brassicales: an update on chromosomal evolution and ancient polyploidy. Plant Systematics and Evolution, 304(6), 757–762. https://doi.org/10.1007/s00606-018-1507-2
1633. Mabry, M. E., Turner-Hissong, S. D., Gallagher, E. Y., McAlvay, A. C., An, H., Edger, P. P., Moore, J. D., Pink, D. A. C., Teakle, G. R., Stevens, C. J., Barker, G., Labate, J., Fuller, D. Q., Allaby, R. G., Beissinger, T., Decker, J. E., Gore, M. A., & Pires, J. C. (2021). The Evolutionary History of Wild, Domesticated, and Feral Brassica oleracea (Brassicaceae). Molecular Biology and Evolution, 38(10), 4419–4434. https://doi.org/10.1093/molbev/msab183
1634. Mabry, M. E., Brose, J. M., Blischak, P. D., Sutherland, B., Dismukes, W. T., Bottoms, C. A., Edger, P. P., Washburn, J. D., An, H., Hall, J. C., McKain, M. R., Al‐Shehbaz, I., Barker, M. S., Schranz, M. E., Conant, G. C., & Pires, J. C. (2020). Phylogeny and multiple independent whole‐genome duplication events in the Brassicales. American Journal of Botany, 107(8), 1148–1164. https://doi.org/10.1002/ajb2.1514
Page 233. The function of mustard oils. Note that there are many potential functions, including in signaling, defense, etc. This is a good example of the defensive functions that these chemicals can play.
1635. Lichtenstein, E. P., Strong, F. M., & Morgan, D. G. (1962). Naturally Occurring Insecticides, Identification of 2-Phenylethylisothiocyanate As an Insecticide Occurring Naturally in the Edible Part of Turnips. Journal of Agricultural and Food Chemistry, 10(1), 30–33. https://doi.org/10.1021/jf60119a009
1636. Lichtenstein, E. P., Morgan, D. G., & Mueller, C. H. (1964). Insecticides in Nature, Naturally Occurring Insecticides in Cruciferous Crops. Journal of Agricultural and Food Chemistry, 12(2), 158–161. https://doi.org/10.1021/jf60132a017
1638. Matile, Ph. (1980). „Die Senfolbombe“: Zur Kompartimentierung des Myrosinasesystems. Biochemie Und Physiologie Der Pflanzen, 175(8–9), 722–731. https://doi.org/10.1016/S0015-3796(80)80059-X
1639. Li, Q., Eigenbrode, S. D., Stringam, G. R., & Thiagarajah, M. R. (2000). Feeding and Growth of Plutella xylostella and Spodoptera eridania on Brassica juncea with Varying Glucosinolate Concentrations and Myrosinase Activities. Journal of Chemical Ecology, 26(10), 2401–2419. https://doi.org/10.1023/A:1005535129399
1640. Ratzka, A., Vogel, H., Kliebenstein, D. J., Mitchell-Olds, T., & Kroymann, J. (2002). Disarming the mustard oil bomb. Proceedings of the National Academy of Sciences, 99(17), 11223–11228. https://doi.org/10.1073/pnas.172112899
1642. Kazana, E., Pope, T. W., Tibbles, L., Bridges, M., Pickett, J. A., Bones, A. M., Powell, G., & Rossiter, J. T. (2007). The cabbage aphid: a walking mustard oil bomb. Proceedings of the Royal Society B: Biological Sciences, 274(1623), 2271–2277. https://doi.org/10.1098/rspb.2007.0237
1643. Hunziker, P., Lambertz, S. K., Weber, K., Crocoll, C., Halkier, B. A., & Schulz, A. (2021). Herbivore feeding preference corroborates optimal defense theory for specialized metabolites within plants. Proceedings of the National Academy of Sciences, 118(47). https://doi.org/10.1073/pnas.2111977118
Page 233. This is why.
1644. Bell, L., Oloyede, O. O., Lignou, S., Wagstaff, C., & Methven, L. (2018). Taste and Flavor Perceptions of Glucosinolates, Isothiocyanates, and Related Compounds. Molecular Nutrition & Food Research, 62(18). https://doi.org/10.1002/mnfr.201700990
Page 234. Most commercially available wasabi. See this quote from Köppel and Bucher (2016): “In ten of the products, which claim to contain wasabi, no wasabi signal was detected. In consequence, we concluded that the product does not contain wasabi and is therefore fraudulent. In all of these products, horseradish was detected, confirming correct DNA isolation and amplification.” The algae used to color “wasabi” paste green is often Spirulina spp. Other coloring agents are also used.
1645. Chadwick, C. I., Lumpkin, T. A., & Elberson, L. R. (1993). The botany, uses and production of Wasabia japonica (Miq.) (Cruciferae) Matsum. Economic Botany, 47(2), 113–135. https://doi.org/10.1007/BF02862015
1646. Bewicke, D., & Potter, B. A. (2009). Chlorella: the emerald food. Ronin Publishing.
1647. Koller, M., Muhr, A., & Braunegg, G. (2014). Microalgae as versatile cellular factories for valued products. Algal Research, 6, 52–63. https://doi.org/10.1016/j.algal.2014.09.002
1648. Köppel, R., & Bucher, T. B. (2016). Duplex real-time PCR for the determination of wasabi (Eutrema wasabi) contents in horseradish (Armoracia rusticana) products applying the ΔΔct-method. European Food Research and Technology, 242(7), 1111–1115. https://doi.org/10.1007/s00217-015-2615-7
1649. Herrera, M., Viera, I., & Roca, M. (2023). Study of the authentic composition of the novel green foods: Food colorants and coloring foods. Food Research International, 170, 112974. https://doi.org/10.1016/j.foodres.2023.112974
1653. Ciska, E., & Pathak, D. R. (2004). Glucosinolate Derivatives in Stored Fermented Cabbage. Journal of Agricultural and Food Chemistry, 52(26), 7938–7943. https://doi.org/10.1021/jf048986+
1654. Kim, S.-Y., Yang, J., Dang, Y.-M., & Ha, J.-H. (2022). Effect of fermentation stages on glucosinolate profiles in kimchi: Quantification of 14 intact glucosinolates using ultra-performance liquid chromatography-tandem mass spectrometry. Food Chemistry: X, 15, 100417. https://doi.org/10.1016/j.fochx.2022.100417
Page 235. Our gut bacteria have other plans. There are two important points. The glucosinolate “protoxin” is hydrolyzed by glucosidases from bacteria in the human gut, producing, among other products, isothiocyanates, which are the “mustard oils.” These toxins are then further degraded by hydrolases in some bacteria into hydrogen sulfide, carbon dioxide, and an amine as was first reported by Tang et al. (1972).
1655. Tang, C.-S., Bhothipaksa, K., & Frank, H. A. (1972). Bacterial Degradation of Benzyl Isothiocyanate. Applied Microbiology, 23(6), 1145–1148. https://doi.org/10.1128/am.23.6.1145-1148.1972
1656. Fenwick, G. R., Heaney, R. K., Mullin, W. J., & VanEtten, C. H. (1983). Glucosinolates and their breakdown products in food and food plants. C R C Critical Reviews in Food Science and Nutrition, 18(2), 123–201. https://doi.org/10.1080/10408398209527361
1657. Li, F., Hullar, M. A. J., Beresford, S. A. A., & Lampe, J. W. (2011). Variation of glucoraphanin metabolism in vivo and ex vivo by human gut bacteria. British Journal of Nutrition, 106(3), 408–416. https://doi.org/10.1017/S0007114511000274
1658. Luang‐In, V., Narbad, A., Nueno‐Palop, C., Mithen, R., Bennett, M., & Rossiter, J. T. (2014). The metabolism of methylsulfinylalkyl‐ and methylthioalkyl‐glucosinolates by a selection of human gut bacteria. Molecular Nutrition & Food Research, 58(4), 875–883. https://doi.org/10.1002/mnfr.201300377
1659. Liou, C. S., Sirk, S. J., Diaz, C. A. C., Klein, A. P., Fischer, C. R., Higginbottom, S. K., Erez, A., Donia, M. S., Sonnenburg, J. L., & Sattely, E. S. (2020). A Metabolic Pathway for Activation of Dietary Glucosinolates by a Human Gut Symbiont. Cell, 180(4), 717-728.e19. https://doi.org/10.1016/j.cell.2020.01.023
1660. Watanabe, H., Usami, R., Kishino, S., Osada, K., Aoki, Y., Morisaka, H., Takahashi, M., Izumi, Y., Bamba, T., Aoki, W., Suganuma, H., & Ogawa, J. (2021). Enzyme systems involved in glucosinolate metabolism in Companilactobacillus farciminis KB1089. Scientific Reports, 11(1), 23715. https://doi.org/10.1038/s41598-021-03064-7
Page 234. Not only are mustard oils.
1661. Fahey, J. W., Haristoy, X., Dolan, P. M., Kensler, T. W., Scholtus, I., Stephenson, K. K., Talalay, P., & Lozniewski, A. (2002). Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[ a ]pyrene-induced stomach tumors. Proceedings of the National Academy of Sciences, 99(11), 7610–7615. https://doi.org/10.1073/pnas.112203099
1662. Zhao, J., Moore, A. N., Clifton, G. L., & Dash, P. K. (2005). Sulforaphane enhances aquaporin-4 expression and decreases cerebral edema following traumatic brain injury. Journal of Neuroscience Research, 82(4), 499–506. https://doi.org/10.1002/jnr.20649
1663. Zhao, J., Moore, A. N., Redell, J. B., & Dash, P. K. (2007). Enhancing Expression of Nrf2-Driven Genes Protects the Blood–Brain Barrier after Brain Injury. The Journal of Neuroscience, 27(38), 10240–10248. https://doi.org/10.1523/JNEUROSCI.1683-07.2007
1664. Dash, P. K., Zhao, J., Orsi, S. A., Zhang, M., & Moore, A. N. (2009). Sulforaphane improves cognitive function administered following traumatic brain injury. Neuroscience Letters, 460(2), 103–107. https://doi.org/10.1016/j.neulet.2009.04.028
1665. Kensler, T. W., Ng, D., Carmella, S. G., Chen, M., Jacobson, L. P., Muñoz, A., Egner, P. A., Chen, J. G., Qian, G. S., Chen, T. Y., Fahey, J. W., Talalay, P., Groopman, J. D., Yuan, J.-M., & Hecht, S. S. (2012). Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China. Carcinogenesis, 33(1), 101–107. https://doi.org/10.1093/carcin/bgr229
1666. Houghton, C. A., Fassett, R. G., & Coombes, J. S. (2013). Sulforaphane: translational research from laboratory bench to clinic. Nutrition Reviews, 71(11), 709–726. https://doi.org/10.1111/nure.12060
1667. Egner, P. A., Chen, J.-G., Zarth, A. T., Ng, D. K., Wang, J.-B., Kensler, K. H., Jacobson, L. P., Muñoz, A., Johnson, J. L., Groopman, J. D., Fahey, J. W., Talalay, P., Zhu, J., Chen, T.-Y., Qian, G.-S., Carmella, S. G., Hecht, S. S., & Kensler, T. W. (2014). Rapid and Sustainable Detoxication of Airborne Pollutants by Broccoli Sprout Beverage: Results of a Randomized Clinical Trial in China. Cancer Prevention Research, 7(8), 813–823. https://doi.org/10.1158/1940-6207.CAPR-14-0103
1668. Singh, K., Connors, S. L., Macklin, E. A., Smith, K. D., Fahey, J. W., Talalay, P., & Zimmerman, A. W. (2014). Sulforaphane treatment of autism spectrum disorder (ASD). Proceedings of the National Academy of Sciences, 111(43), 15550–15555. https://doi.org/10.1073/pnas.1416940111
1669. Singh, K., & W. Zimmerman, A. (2016). Sulforaphane Treatment of Young Men with Autism Spectrum Disorder. CNS & Neurological Disorders - Drug Targets, 15(5), 597–601. https://doi.org/10.2174/1871527315666160413122525
1670. Zhou, Q., Chen, B., Wang, X., Wu, L., Yang, Y., Cheng, X., Hu, Z., Cai, X., Yang, J., Sun, X., Lu, W., Yan, H., Chen, J., Ye, J., Shen, J., & Cao, P. (2016). Sulforaphane protects against rotenone-induced neurotoxicity in vivo: Involvement of the mTOR, Nrf2 and autophagy pathways. Scientific Reports, 6(1), 32206. https://doi.org/10.1038/srep32206
1671. Liu, F., Huang, J., Hei, G., Wu, R., & Liu, Z. (2020). Effects of sulforaphane on cognitive function in patients with frontal brain damage: study protocol for a randomised controlled trial. BMJ Open, 10(10), e037543. https://doi.org/10.1136/bmjopen-2020-037543
Page 234 and 235. Other studies. Note an earlier study did examine the effects of sulforaphane (an isothiocyanate) on lifespan in Drosophila melanogaster.
1674. Li, Y. M., Chan, H. Y. E., Yao, X. Q., Huang, Y., & Chen, Z. Y. (2008). Green tea catechins and broccoli reduce fat-induced mortality in Drosophila melanogaster. The Journal of Nutritional Biochemistry, 19(6), 376–383. https://doi.org/10.1016/j.jnutbio.2007.05.009
1675. Villatoro-Pulido, M., Font, R., Saha, S., Obregón-Cano, S., Anter, J., Muñoz-Serrano, A., de Haro-Bailón, A., Alonso-Moraga, A., & del Río- Celestino, M. (2012). In vivo biological activity of rocket extracts (Eruca vesicaria subsp. sativa (Miller) Thell) and sulforaphane. Food and Chemical Toxicology, 50(5), 1384–1392. https://doi.org/10.1016/j.fct.2012.02.017
1676. Grünwald, S., Stellzig, J., Adam, I. v., Weber, K., Binger, S., Boll, M., Knorr, E., Twyman, R. M., Vilcinskas, A., & Wenzel, U. (2013). Longevity in the red flour beetle Tribolium castaneum is enhanced by broccoli and depends on nrf-2, jnk-1 and foxo-1 homologous genes. Genes & nutrition, 8, 439-448. https://doi.org/10.1007/s12263-012-0330-6
1677. Qi, Z., Ji, H., Le, M., Li, H., Wieland, A., Bauer, S., Liu, L., Wink, M., & Herr, I. (2021). Sulforaphane promotes C. elegans longevity and healthspan via DAF-16/DAF-2 insulin/IGF-1 signaling. Aging, 13(2), 1649–1670. https://doi.org/10.18632/aging.202512
Page 235. Called Nrf2.
1678. Moi, P., Chan, K., Asunis, I., Cao, A., & Kan, Y. W. (1994). Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proceedings of the National Academy of Sciences, 91(21), 9926–9930. https://doi.org/10.1073/pnas.91.21.9926
1679. Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002). Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proceedings of the National Academy of Sciences, 99(18), 11908–11913. https://doi.org/10.1073/pnas.172398899
1680. Zhang, D. D., & Hannink, M. (2003). Distinct Cysteine Residues in Keap1 Are Required for Keap1-Dependent Ubiquitination of Nrf2 and for Stabilization of Nrf2 by Chemopreventive Agents and Oxidative Stress. Molecular and Cellular Biology, 23(22), 8137–8151. https://doi.org/10.1128/MCB.23.22.8137-8151.2003
1681. Motohashi, H., Katsuoka, F., Engel, J. D., & Yamamoto, M. (2004). Small Maf proteins serve as transcriptional cofactors for keratinocyte differentiation in the Keap1–Nrf2 regulatory pathway. Proceedings of the National Academy of Sciences, 101(17), 6379–6384. https://doi.org/10.1073/pnas.0305902101
1682. McMahon, M., Thomas, N., Itoh, K., Yamamoto, M., & Hayes, J. D. (2004). Redox-regulated Turnover of Nrf2 Is Determined by at Least Two Separate Protein Domains, the Redox-sensitive Neh2 Degron and the Redox-insensitive Neh6 Degron. Journal of Biological Chemistry, 279(30), 31556–31567. https://doi.org/10.1074/jbc.M403061200
Page 235. Another hint about why. Rather than a single study, there are actually a series of studies that have used both paraquat and rotenone in the diet as generators of reactive oxygen species in the context of lifespan, stress, and/or Parkinson’s Disease in Drosophila melanogaster and mice. Other studies then tested how pre-treatment with extracts from mustards or sulforaphane itself extends lifespan and/or rescues Parksinon’s Disease-like effects in mutant model animals. As the Coulom and Birman (2004) study suggests: “The selectivity of rotenone action is likely attributable to a specific sensitivity of Drosophila dopaminergic neurons to reactive oxygen species and oxidative damages.”
1683. Coulom, H., & Birman, S. (2004). Chronic Exposure to Rotenone Models Sporadic Parkinson’s Disease in Drosophila melanogaster. The Journal of Neuroscience, 24(48), 10993–10998. https://doi.org/10.1523/JNEUROSCI.2993-04.2004
1684. Trinh, K., Moore, K., Wes, P. D., Muchowski, P. J., Dey, J., Andrews, L., & Pallanck, L. J. (2008). Induction of the Phase II Detoxification Pathway Suppresses Neuron Loss in Drosophila Models of Parkinson’s Disease. The Journal of Neuroscience, 28(2), 465–472. https://doi.org/10.1523/JNEUROSCI.4778-07.2008
1685. Li, Y. M., Chan, H. Y. E., Huang, Y., & Chen, Z. Y. (2008). Broccoli ( Brassica oleracea var. botrytis L.) improves the survival and up‐regulates endogenous antioxidant enzymes in Drosophila melanogaster challenged with reactive oxygen species. Journal of the Science of Food and Agriculture, 88(3), 499–506. https://doi.org/10.1002/jsfa.3113
1686. Lyles, J. T., Luo, L., Liu, K., Jones, D. P., Jones, R. M., & Quave, C. L. (2021). Cruciferous vegetables ( Brassica oleracea ) confer cytoprotective effects in Drosophila intestines. Gut Microbes, 13(1). https://doi.org/10.1080/19490976.2021.1921926
1687. Zhou, Q., Chen, B., Wang, X., Wu, L., Yang, Y., Cheng, X., Hu, Z., Cai, X., Yang, J., Sun, X., Lu, W., Yan, H., Chen, J., Ye, J., Shen, J., & Cao, P. (2016). Sulforaphane protects against rotenone-induced neurotoxicity in vivo: Involvement of the mTOR, Nrf2 and autophagy pathways. Scientific Reports, 6(1), 32206. https://doi.org/10.1038/srep32206
1688. Cheng, J., Wang, H., Bartlett, M., Stevenson, D., Pan, Y., Ho, M. S., & Ren, Y. (2021). Antioxidant Blend of Curcumin and Broccoli Seed Extract Exhibits Protective Effect on Neurodegeneration and Promotes Drosophila Lifespan. ASN Neuro, 13, 175909142110150. https://doi.org/10.1177/17590914211015033
1689. Lawana, V., & Cannon, J. R. (2020). Rotenone neurotoxicity: Relevance to Parkinson’s disease. In M. Aschner & L. G. Costa (Eds.), Advances in Neurotoxicology (Vol. 4, pp. 209–254). Academic Press. https://doi.org/https://doi.org/10.1016/bs.ant.2019.11.004
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Page 235. Rotenone can produce.
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Page 235. Some studies show.
1702. Trinh, K., Moore, K., Wes, P. D., Muchowski, P. J., Dey, J., Andrews, L., & Pallanck, L. J. (2008). Induction of the Phase II Detoxification Pathway Suppresses Neuron Loss in Drosophila Models of Parkinson’s Disease. The Journal of Neuroscience, 28(2), 465–472. https://doi.org/10.1523/JNEUROSCI.4778-07.2008
1703. Morroni, F., Tarozzi, A., Sita, G., Bolondi, C., Zolezzi Moraga, J. M., Cantelli-Forti, G., & Hrelia, P. (2013). Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson’s disease. NeuroToxicology, 36, 63–71. https://doi.org/10.1016/j.neuro.2013.03.004
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Page 235 and 236. Scientists have dug deeper.
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Page 251. As ethnobotanist Gary Nabhan.
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Page 251 and 252. Paul Freedman. This reference supports the next seven paragraphs.
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Page 252. Out of Mithridate’s paranoia.
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Page 252. In the first century. See from Karaberopoulus et al. (2012) reference below: “But Galen did not just administer his theriac, he also experimented with it on animals. In De Theriaca ad Pisonem he describes how he took roosters and divided them into two groups: in one group he gave the theriac and in the other group he did not. Then he brought both groups into contact with snakes; Galen observed that the roosters who had not been given the theriac died immediately after being bitten, whereas those who had been given the theriac survived. Moreover, he points out that this experiment could be used in cases where someone wants to make sure whether a theriac is in its natural form or has been adulterated.”
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1874. Freedman, P. (2008). Out of the East: spices and the medieval imagination. Yale University Press.
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1910. Freedman, P. (2008). Out of the East: spices and the medieval imagination. Yale University Press.
1911. Turner, J. (2008). Spice: the History of a Temptation. Vintage.
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Page 264. Like the isoprene. These references support the paragraphs through the end of this chapter.
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1986. Cuvi, N. (2011). The Cinchona Program (1940-1945): science and imperialism in the exploitation of a medicinal plant. Dynamis, 31(1), 183–206. https://doi.org/10.4321/S0211-95362011000100009
1987. Goss, A. (2014). Building the world’s supply of quinine: Dutch colonialism and the origins of a global pharmaceutical industry. Endeavour, 38(1), 8–18. https://doi.org/10.1016/j.endeavour.2013.10.002
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Page 266. Perhaps more cryptically but arguably.
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Page 266. But at the beginning. These references support the next two paragraphs.
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2005. Berger, M. T. (1993). Civilising the South: The US Rise to Hegemony in the Americas and the Roots of “Latin American Studies” 1898-1945. Bulletin of Latin American Research, 12(1), 1. https://doi.org/10.2307/3338811
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2008. Marcilhacy, D. (2022). 1914, between two oceans, between two empires: a turning point for Latin America. National Identities, 24(1), 21–37. https://doi.org/10.1080/14608944.2020.1738365
Chapter 13. The Future Pharmacopoeia
Page 268. There is grandeur in this view of life. This is the last quote in the chapter XIV of Charle’s Darwin’s masterpiece that usually is known by the abbreviated title On the Origin of Species. This particular quote is from the first British edition published in 1859 and three additional words were added to that quote such that by 1872 (the last edition) the words “by the Creator” were inserted after “breathed into” for reasons covered by historians.
2009. Darwin, C. R. (1859). On the Origin of Species by Means of Natural Selection, or the Preservation of Favoured Races in the Struggle for Life. London: Murray. [1st ed.]
Page 269. Most of these natural toxins. The notes that follow provide context and support for the entire paragraph that starts with this sentence and the following one that begins: Scientists have shown that.
In 1976 botanist Donald Levin published the first truly quantitative study on how plant secondary chemical diversity correlates with latitude such that there are fewer made by plants at the poles or at high elevation than in the tropics or low elevation. He first found that across the planet’s latitudes, the percentage of plants with alkaloids increased from the poles to the tropics (like spice use in us). The proportion of plant species from tropical countries containing alkaloids (45%) is nearly double the proportion from temperate countries containing alkaloids (27%). In an attempt tease apart why, Levin cleverly used the German polymath Alexander von Humboldt’s observation that the biomes of the planet that so predictably change across latitude, from the rainforests of the tropics to the tundra of the poles, could also be mirrored across changes in altitude, from the base of a tall tropical mountain to its summit. Levin used an alkaloid dataset across such an elevational gradient in the large tropical island of Papua New Guinea, which fit the bill owing to its lush lowland rainforests and treeless alpine habitats. Sure enough, he found that plant species bearing alkaloids were more prevalent in the three rainforest communities, with the most (21.5%) in the lowland rain forest and the fewest in the subalpine and alpine biomes (0%)—although my guess is that the instruments may not have been sensitive enough for us to really know that there aren’t any in the plants he tested in the latter. Other notable papers buttressing this paragraph in the book are also listed below. One by Levin and York also concludes that the toxicity of the alkaloids made by tropical plants is higher than those made by temperate plants (and that there were no salient differences in toxicity in herbaceous vs. wood plants in that regard). This further supports the working hypothesis that the strength of biotic interactions is higher in the tropics than the temperate zones. In a review, Coley and Barone in 1996 concluded that rates of herbivory are higher in the tropics than in temperate zones. In a series of papers Janzen also proposes some specific hypotheses as to why this is generally the case. MacArthur and Wilson propose why there may be more species in the tropics than in the temperate zone. A general review of whether biotic interactions were stronger in the tropics than the temperate zone was published by Schemske et al. in 2009 and the analysis was in support of this working hypothesis.
2010. Levin, D. A. (1976). Alkaloid-Bearing Plants: An Ecogeographic Perspective. The American Naturalist, 110(972), 261–284. https://doi.org/10.1086/283063
2012. Levin, D. A., & York, B. M. (1978). The toxicity of plant alkaloids: an Ecogeographic perspective. Biochemical Systematics and Ecology, 6(1), 61–76. https://doi.org/10.1016/0305-1978(78)90026-1
2013. Coley, P. D., & Barone, J. A. (1996). Herbivory and Plant Defenses in Tropical Forests. Annual Review of Ecology and Systematics, 27, 305–335. http://www.jstor.org/stable/2097237
2014. Janzen, D. H. (1968). Host Plants as Islands in Evolutionary and Contemporary Time. The American Naturalist, 102(928), 592–595. http://www.jstor.org/stable/2459347
2015. Janzen, D. H. (1973). Community structure of secondary compounds in plants. In Chemistry in Evolution and Systematics, ed T. Swain, pp. 529-38. New York: Russak.
2016. Janzen, D. H. (1974). Tropical Blackwater Rivers, Animals, and Mast Fruiting by the Dipterocarpaceae. Biotropica, 6(2), 69. https://doi.org/10.2307/2989823
2017. Hutchinson, G. E. (1959). Homage to Santa Rosalia or Why Are There So Many Kinds of Animals? The American Naturalist, 93(870), 145–159. http://www.jstor.org/stable/2458768
2018. Schemske, D. W., Mittelbach, G. G., Cornell, H. v., Sobel, J. M., & Roy, K. (2009). Is There a Latitudinal Gradient in the Importance of Biotic Interactions? Annual Review of Ecology, Evolution, and Systematics, 40(1), 245–269. https://doi.org/10.1146/annurev.ecolsys.39.110707.173430
Pages 269-270. If you or a loved one. This section also applies to the four paragraphs that follow the first. Note that the quote “West Indian shrub” is from the Noble et al. paper from 1958 below.
2022. Duffin, J. (2000). Poisoning the Spindle: Serendipity and Discovery of the Anti-Tumor Properties of the Vinca Alkaloids. Canadian Bulletin of Medical History, 17(1), 155–192. https://doi.org/10.3138/cbmh.17.1.155
2023. Noble, R. L., Beer, C. T., & Cutts, J. H. (1958). Role of chance observations in chemotherapy: Vinca rosea. Annals of the New York Academy of Sciences, 76(3), 882–894. https://doi.org/10.1111/j.1749-6632.1958.tb54906.x
2024. O’Connor, S. E., & Maresh, J. J. (2006). Chemistry and biology of monoterpene indole alkaloid biosynthesis. Natural Product Reports, 23(4), 532. https://doi.org/10.1039/b512615k
2025. Kumar, S., Singh, B., & Singh, R. (2022). Catharanthus roseus (L.) G. Don: A review of its ethnobotany, phytochemistry, ethnopharmacology and toxicities. Journal of Ethnopharmacology, 284, 114647. https://doi.org/10.1016/j.jep.2021.114647
2026. Caputi, L., Franke, J., Farrow, S. C., Chung, K., Payne, R. M. E., Nguyen, T.-D., Dang, T.-T. T., Soares Teto Carqueijeiro, I., Koudounas, K., Dugé de Bernonville, T., Ameyaw, B., Jones, D. M., Vieira, I. J. C., Courdavault, V., & O’Connor, S. E. (2018). Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle. Science, 360(6394), 1235–1239. https://doi.org/10.1126/science.aat4100
Page 270. Many important drugs come from weedy species. These references also apply to the next two paragraphs.
2027. Dufour, D. L. (1990). Use of Tropical Rainforests by Native Amazonians. BioScience, 40(9), 652. https://doi.org/10.2307/1311432
2028. Voeks, R. A. (2004). Disturbance Pharmacopoeias: Medicine and Myth from the Humid Tropics. Annals of the Association of American Geographers, 94(4), 868–888. https://doi.org/10.1111/j.1467-8306.2004.00439.x
2029. Ellis, E. C., Gauthier, N., Klein Goldewijk, K., Bliege Bird, R., Boivin, N., Díaz, S., Fuller, D. Q., Gill, J. L., Kaplan, J. O., Kingston, N., Locke, H., McMichael, C. N. H., Ranco, D., Rick, T. C., Shaw, M. R., Stephens, L., Svenning, J.-C., & Watson, J. E. M. (2021). People have shaped most of terrestrial nature for at least 12,000 years. Proceedings of the National Academy of Sciences, 118(17). https://doi.org/10.1073/pnas.2023483118
2030. Bennett, B. C. (2007). Doctrine of Signatures: An Explanation of Medicinal Plant Discovery or Dissemination of Knowledge? Economic Botany, 61(3), 246–255. http://www.jstor.org/stable/4257221
2031. Chazdon, R. L., & Guariguata, M. R. (2016). Natural regeneration as a tool for large‐scale forest restoration in the tropics: prospects and challenges. Biotropica, 48(6), 716–730. https://doi.org/10.1111/btp.12381
2032. Voeks, R. A. (2018). The Ethnobotany of Eden: Rethinking the Jungle Medicine Narrative. University of Chicago Press: Chicago.
2033. Roberts, P. (2021). Jungle: How Tropical Forests Shaped the World and Us. Viking Press: New York.
2034. Canuto, M. A., Estrada-Belli, F., Garrison, T. G., Houston, S. D., Acuña, M. J., Kováč, M., Marken, D., Nondédéo, P., Auld-Thomas, L., Castanet, C., Chatelain, D., Chiriboga, C. R., Drápela, T., Lieskovský, T., Tokovinine, A., Velasquez, A., Fernández-Díaz, J. C., & Shrestha, R. (2018). Ancient lowland Maya complexity as revealed by airborne laser scanning of northern Guatemala. Science, 361(6409). https://doi.org/10.1126/science.aau0137
2035. Inomata, T., Triadan, D., Vázquez López, V. A., Fernandez-Diaz, J. C., Omori, T., Méndez Bauer, M. B., García Hernández, M., Beach, T., Cagnato, C., Aoyama, K., & Nasu, H. (2020). Monumental architecture at Aguada Fénix and the rise of Maya civilization. Nature, 582(7813), 530–533. https://doi.org/10.1038/s41586-020-2343-4
2036. Ringle, W. M., Gallareta Negrón, T., May Ciau, R., Seligson, K. E., Fernandez-Diaz, J. C., & Ortegón Zapata, D. (2021). Lidar survey of ancient Maya settlement in the Puuc region of Yucatan, Mexico. PLOS ONE, 16(4), e0249314. https://doi.org/10.1371/journal.pone.0249314
2037. Prümers, H., Betancourt, C. J., Iriarte, J., Robinson, M., & Schaich, M. (2022). Lidar reveals pre-Hispanic low-density urbanism in the Bolivian Amazon. Nature, 606(7913), 325–328. https://doi.org/10.1038/s41586-022-04780-4
Page 271. Our past actions have finally.
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2039. Lovejoy, T. E. and L. Hannah, Eds. 2019. Biodiversity and Climate Change: Transforming the Biosphere. Yale Univ. Press: New Haven.
2040. Leal Filho, W., Matandirotya, N. R., Lütz, J. M., Alemu, E. A., Brearley, F. Q., Baidoo, A. A., Kateka, A., Ogendi, G. M., Adane, G. B., Emiru, N., & Mbih, R. A. (2021). Impacts of climate change to African indigenous communities and examples of adaptation responses. Nature Communications, 12(1), 6224. https://doi.org/10.1038/s41467-021-26540-0
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Page 272. As we toured museums. These references apply to the next four paragraphs well.
2046. Brief description from the Victoria and Albert Museum: “Tapestry 'The Three Fates' ('The Triumph of Death'), Flemish, early 16th century” see: https://collections.vam.ac.uk/item/O72702/the-three-fates-tapestry-unknown/ Gallery Label from the V&A Museum: “THE TRIUMPH OF DEATH or THE THREE FATES The three fates, Clotho, Lachesis and Atropos, who spin, draw out and cut the thread of Life, represent Death in this tapestry, as they triumph over the fallen body of Chastity. This is the third subject in Petrarch's poem The Triumphs. First, Love triumphs; then Love is overcome by Chastity, Chastity by Death, Death by Fame, Fame by Time and Time by Eternity. FLEMISH (probably BRUSSELS); c. 1510-20 Museum number 65-1866 (c. 2003).”
2052. Mann, M. (2023). Our Fragile Moment: How Lessons from the Earth’s Past Can Help Us Survive the Climate Crisis. Hachette: New York.
2053. Hernandez, J. (2022). Fresh Banana Leaves: Healing Indigenous Landscapes through Indigenous Science. North Atlantic: Berkeley.
2054. Dinerstein, E., Joshi, A. R., Vynne, C., Lee, A. T. L., Pharand-Deschênes, F., França, M., Fernando, S., Birch, T., Burkart, K., Asner, G. P., & Olson, D. (2020). A “Global Safety Net” to reverse biodiversity loss and stabilize Earth’s climate. Science Advances, 6(36). https://doi.org/10.1126/sciadv.abb2824
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