malaria, leprosy, arthritis, dropsy, twilight sleep, cortisone, aspirin, prostaglandins ….

1. Plants, medicine, and culture M. Keffer Waterloo-Oxford may, 2001 • malaria, leprosy, arthritis, dropsy, twilight sleep, cortisone, aspirin, prostaglandins …. • ethnobotany, bioprospecting, and rain forest degradation • social and cultural aspects of healing shown by plant remedies • comparison of healing styles • plants and religious activity • toxins and drugs • Doctrine of Signatures

2. Plants, medicine, and culture stay tuned for future presentations on: • Plants of economic importance • spices, flavourings, and trade • coffee, tea, saffron, cinnamon, nutmeg, cloves and clove oil, coconut • the Moluccas and the Spice Wars • industrials -- rubber, cotton • rubber and World War II • structural materials: wood, palm • lignins and structural strength • alternate food sources: algae • Plants as biochemical factories • phytoremediation, bioremediation, and Living Machines • oxygenators and water purifiers for space travel • genetic engineering and new uses for tobacco

3. ethnobotany

4. Ethnobotany 1 • the study of plants learned from the people who use them • often includes medicinal plants • often includes the study of indigenous peoples • research methods involve living with the people who use the plants, and learning their methods from them • in many cases the proper use of the plants is wrapped up with their everyday lives, and therefore difficult to explain to foreigners • e.g. it’s hard to walk into the forest and find a cure for cancer when the local people don’t even have a word for cancer • therefore foreigners like us must go to learn in THEIR environment, on THEIR terms.

5. threats to ethnobotanical knowledge • Threats include: • expansion of “civilized” cultures into their habitat • mining • transport • slash&burn agriculture • pollution • attrition • (young members of tribes leaving and not returning to learn from their elders -- no one to carry on the traditions)

6. it’s not just the plants; it’s how they are used, their preparation, their admixtures, and knowledge of fine differences between them (closely related plants, plants that resemble each other at certain stages of the year) in most cases this knowledge is NOT written down ANYWHERE it is part of an oral tradition -- meaning it is only passed from person to person orally, through teaching not all peoples have writing even if they did, for most, their secrets are sacred and not to be told to just anyone Currently there are new diseases for which there is no known cure also some existing diseases have become resistant to antibiotics the forest may be the best place to learn about drug substances forests are disappearing, and with them, the people who know how to use these plants Note: an admixture is something added to the active ingredient to alter it in some way make it less toxic reduce its side effects increase its potency by allowing it to enter the bloodstream more quickly allow it to cross the blood-brain barrier Significance of ethnobotany

7. Malaria life cycle • parasites live in gut of female Anopheles mosquito • when mosquito bites, it injects fluid to act as anticoagulant and anaesthetic • parasites enter human bloodstream • travel to liver for another stage • enter bloodstream and replicate in red blood cells • burst the RBC when they reach large enough numbers and size • when another mosquito bites, parasites move back into the mosquito gut to start the next round of replication

8. Malaria info from the WHO (World Health Organization) • Malaria kills more people than any other communicable disease except tuberculosis • Caused by a protist parasite that lives both in mosquitoes and humans • since it is not a bacteria, antibiotics are NOT effective against it • it is curable if promptly treated • multi-drug resistant strains are now becoming more prevalent • major problem in areas covering 40% of the world’s population • symptoms: • fever, shivering, pain in the joints, headache, repeated vomiting, convulsions, coma, severe anemia • recurrent cycles of shivering and fever that coincide with the release of parasites within the blood • kills over 3000 children per day worldwide -- far more than HIV • a single bout of infection usually costs the equivalent of 10 working days • ref: http://www.who.int/inf-fs/en/fact094.html

9. increased risk of malaria a hidden risk of global warming….?

10. cinchona • Malaria is the one of the top killers in the world • Evidence suggests it has been a concern at least back to 500 BC • there were lots of “remedies” but no real cure • the Cinchona tree from South America provided quinine • for several hundred years it was the only cure • Significance: • At this time European colonialism was expanding explosively into the Americas, Africa, India, Indonesia, and other areas of Asia. • All these expansions were partially fuelled by the “discovery” of quinine • Without it it is unlikely that expansion would have occurred nearly as quickly, since many colonialists were killed by malaria

11. caused by mycobacterium similar to the one that causes tuberculosis infects and kills peripheral nerves (extremities) leads to numbness and lack of circulation this often leads to gangrene or muscle damage nasal membranes also often infected - -probably initial entry point of infection leprosy

12. muscle wasting may cause bizarre contortion of joints (first picture) eyes also may be affected -- nerves leading to cornea deteriorate; therefore cornea and other membranes deteriorate cornea become numb, therefore don’t know when something’s in the eye leads to damage of membranes and eventual collapse of the nose and nasal tissue for further information check this link leprosy 2

13. dates to biblical times -- very old disease lepers have traditionally been ostracized (booted out of normal society) and forced to live in leper colonies click here for further info on background social and historical implications of leprosy

14. from an Indian tree only thing found to be effective for leprosy throughout history more recently replaced by dapsone (synthetic derivative) this was ONLY made possible by studying the active principle of the chaulmoogra plant currently there are many strains of M.leprae showing resistance to dapsone click here for more info also check here for specific details about the oil chaulmoogra

15. cancer remedies • Found in Madagascar • from the rosy periwinkle • periwinkle currently almost extinct due to rainforest destruction • vinblastine and vincristine have been isolated from this plant • they are currently among the very few successful treatments for childhood leukemia

16. the original Salix • Native people in North America chewed willow bark to relieve headache • Willow bark is one source of salicylic acid • Salicylic acid has similar pain-relieving and blood-thinning properties as aspirin • However, it also tends to cause stomach upset, and lead to ulcers • By chemically adding an acetyl group (CH3-CH2-) to salicylic acid it is changed to… • AcetylSalicylic Acid (or ASA) Willow blossom

17. prostaglandins • prostaglandins are secreted by most animal tissues • wide array of activities • stimulation or relaxation of smooth muscle • dilation or constriction of blood vessels • stimulation of inflammation responses • enhancement of the perception of pain • aspirin works by inhibiting the synthesis of prostaglandins

18. ASA and other pain relievers • ASA is still one of the best pain relievers for arthritis, muscle pain, etc. • lowers fever, relieves pain, reduces inflammation, and thins the blood • inhibits the formation of blood clots -- therefore used to reduce risk of stroke and CVAs (cardiovascular accidents) • ASA is packaged into many different brands of “aspirin,” as well as cough meds, cold remedies, etc. • The other two main pain relief medications available without a prescription are acetaminophen and ibuprofen -- both reduce prostaglandin action • acetaminophen is the active ingredient in Tylenol and many other headache pills • it has many of the same actions as ASA but does not tend to cause the same amount of gastrointestinal discomfort • acetaminophen does not work as well for reduction of inflammation or blood thinning -- ASA is still the best balance of relief and lack of side effects • acetaminophen is a coal tar derivative

19. Camel blood Camel milk “world’s worst diet”?

20. World’s worst diet 2 • This desert tribe survives on a frothed mixture of blood and milk. • It provides all needed nutrients • but “should” produce a high blood cholesterol level. • However, members of this tribe regularly have among the lowest blood cholesterol levels of any group on earth • Ethnobotanical research found that the members of the tribe add a type of bark to their mixture • Further research suggests that this bark has blood cholesterol-lowering properties.

21. epena and shamanism • This shows a shaman (herbal healer) and his apprentice at the start of a healing ceremony. • Which one do you think is the shaman? • What do you think is happening in the picture, and why?

22. Epena and shamanism 2 • Without diagnostic tools, indigenous peoples have relied on spirit helpers to help them discover what is wrong with a sick person. • Shamans (healers) also ask their spirits to help the sick person get better. • In order to speak with their spirits, shamans often go into a trance • certain drug substances are often used to speed up the process of entering the trance • in the picture, the shaman is the one on the right. • His assistant is blowing a powder, called epena, into the shaman’s nose Within minutes, the shaman will be deeply entranced. (The patient is not in the picture.)

23. Comparison of healing styles

24. Western vs. indigenous pharmacopoeia Note especially the differences for cardiovascular, cancer, and dermatology (skin)

25. connection with religion Ancient Egyptian art showing a god pollinating a papyrus plant Why would gods be associated with plants?

26. hunter-gatherers vs agriculturalists • for hunter-gatherer societies, plants were important but not as important as the spirit of the animals on which they depended • when a society sees something as being extremely important, they tend to deify it -- make it into a god in their art and culture • through this, we can learn about their culture by looking at their religious art • concept of sympathetic magic says that by portraying a thing, they can help to make it happen • example: rain dance • with the agricultural revolution, people realized that their success depended on their plants • stories involving gods were good ways to teach • plants in some cases offered routes to things beyond the normal experience, and therefore became identified with gods

27. poppies

28. Opium and opiates • opium has been used for centuries as a narcotic and a painkiller • when research on brain chemicals began, it was found that the brain produces chemicals that “look” exactly like morphine • the brain chemicals are called endorphins • they are natural pain-killers • morphine has its effect because it happens to have the same shape as the endorphins • morphine and endorphins act as either hormones or neurotransmitters -- affecting the nerve cells they encounter

29. Research significance of drug substances • Understanding the structure of morphine allowed understanding of the receptors in the brain through which morphine functions • one way to understand a pathway is to find an example where the pathway DOESN’T WORK. • Then look at the differences between the one that works and the one that doesn’t. • neurotoxic plant substances show how pathways work by shutting down certain pathways -- they provide a case where the “normal” doesn’t work • example: saxitoxin blocks sodium channels

30. Coca -- very different from cocoa • Coca plant unmodified is an excellent source of calcium and vitamins • many diets in the Andean highlands are deficient in calcium • acts as a mild stimulant -- similar to strong coffee • prevents fatigue and hunger • excellent prevention against altitude sickness (common in the high altitudes of the Andes)

31. coca • Coca became a very popular additive to drinks such as wine • it is still included in Coca-cola • this is the only situation in which it can be legally imported • you won’t find it on the ingredients • it’s allowed for it to be listed as a “natural flavouring.” • many anaesthetics such as novocaine were created based on cocaine and its derivatives

32. Coca -- significance • important historical, social, and religious significance • people feel that it connects them to their land -- they see it as a gift, and to use it responsibly is their way of returning the gift • also seen as sacred reaffirmation that they belong • reminder from their gods to take care of the land

33. Coca -- VERY different from cocaine! • Coca leaves must be treated with strong acids to modify the active ingredients into cocaine -- it is a long process that does NOT occur naturally under any circumstances • many countries have destroyed wild coca growth, and coca plantations, in the attempt to cut down supplies • these efforts are supported and promoted by the US “War on Drugs” • this is in hope of reducing the amount of cocaine coming into the US… BUT: • reduction in supply has the effect of increasing demand • probably does little to reduce the amount of coca funneling through illegal routes • however, this does remove it from “natural” users • further info and source of pictures, click here.

34. calabar, witchcraft, and voodoo

35. Trial By Poison • Trial by Poison was a common way to test a person who was suspected of lying • person would be given calabar beans, which are TOXIC (due to the physostigmine) • person would become very sick, dizzy, would foam at the mouth, and might die. • If the person died, they were obviously guilty • If they did not die, they must have been innocent.

36. papaya • provides papain (meat tenderizer) • also chymopapain (contact lens cleaner and treatment for slipped discs) • Inject enzyme into problem disk • it dissolves the jelly in the disk • This shrinks the disk and relieves pressure on the adjacent nerves • reduces need for back surgery

37. Jimsonweed • also called angel’s trumpet, or • Datura stramonium, or • thorn apple • toxic -- to people and livestock • may be hallucinogenic if properly prepared • attractive flower with nice floral smell • leaves have distinctive unpleasant odour when touched

38. “Jimsonweed” • called Jamestown weed according to legend that soldiers marching through Jamestown were treated to a lunch by the residents • the soldiers spent the next few days variously on the rooftops, in the gutters, and wandering around in a “lunatic state.” • most active ingredient is scopolamine

39. arthritis • Joint disorder that can effectively cripple a person • immune system begins attacking self tissue in the joints • joints become inflamed and sore • this calls even more inflammatory cells • positive feedback cycle • joint surfaces become pitted and misshapen • this further accelerates inflammation • many people have it and there is no cure • otherwise not damaging -- affected people must often live with it for the rest of their lives • can prevent simple tasks -- like driving a car, holding the phone, or opening the aspirin bottle

40. Arthritis and cortisone • 1930s: rheumatoid arthritis patients showed dramatic improvement after jaundice • jaundice is liver disease -- leads to yellowing of the skin and eyes; occurs as a symptom of some other disease, such as hepatitis • also: arthritis would decrease during pregnancy, but come back after birth • hormone called compound E found in both cases • but compoud E was very difficult and expensive to synthesize

41. Cortisol and cortisone • Steroid hormone made by the adrenal cortex • causes: • increase in blood sugar • increase in liver glycogen • increased rate of conversion of protein into carbohydrate • elevates blood sugar by conversion of non-carbohydrate molecules into glucose adrenal gland

42. Cortisone: miracle cure for arthritis? • first test on humans: woman with severe rheumatoid arthritis -- so bad she could hardly move • previously, no treatment had shown any effect • after three days of cortisol injections she could move easily • after eight days of injections her symptoms were mostly “gone”

43. Cortisone: Overall Wonder Drug? • Cortisone increased test animals’ resistance to cold, poisons, and other stresses • Pneumonia symptoms would disappear, although the bacteria causing it was still there (remove the cortisone and the symptoms reappear!) • tuberculosis symptoms would also disappear -- but bacteria still present also • side effects: high blood pressure, excessive hair growth; mental problems; ulcers; brittle bones; fluid retention; obesity; mood swings • Often abused! Athletes with joint injuries find that cortisone injections directly into the joint will reduce swelling and allow them to continue playing • however, this usually leads to further damage of the joint • also can lead to softening of the joint and permanent damage and disability

44. Mexican Yams, cortisone, and Dioscorea • In the 1930s and 40s, there was an intense search for a plant source of cortisone • none were found, but a vine called Strophanthus was found that could produce a substance that could easily be modified to provide cortisone • however, this plant could not be cultivated outside its native jungle (not sure why) • later it was found that certain Mexican yams (Dioscorea) could provide the same substance very cheaply • this is the source of cortisone, progesterone, and estrogen for many birth control pills also

45. cortisone and progesterone • note the similarities between the different substances • for such similar molecules, they produce vastly different effects in the body!

46. Larger bar = more poisonous Huratoxin is more than 10 million times more toxic than cyanide plant toxins

47. distance to herbs • Graph shows amount of walking time necessary for a particular healer to reach a forest large enough to find the plants he needs • the time has increased greatly since 1940 due to forest being cut down in his area

48. may apple • podophyllotoxin for cancer from the North American mayapple

49. Strophanthus vine • produces atropine • also cortisone precursors

50. Digitalis (foxglove) • A relatively common disease in the 16th - early 20th century was called dropsy • caused fluid retention in patients’ feet (swelling, also called edema) • they also had weak hearts and often died of heart failure • it was found that an extract of foxglove would help clear up the disease • foxglove was often grown in gardens for its pretty flowers • “wise women” had known of this cure for a long time • but it didn’t become “valid” until an established (male) doctor started treating patients with it • now known that foxglove contains digitalis • digitalis is, even now, one of our most important drugs for increasing the strength of the heart’s contraction • dropsy occurred due to weakening of the heart -- therefore pumping was not strong enough, and fluids pooled in the lower limbs