Current LectureAGRI 116 1nd Edition Lecture 19 Outline of Last Lecture I. Who discovers medicines in plants? (ethnobotony and pharmacognosy)II. Begin historical use of medicinal plants (continued next Monday)Outline of Current Lecture II. Four Ways Medicines are discovered from PlantsIII. Bioprospecting vs. biopiracy?Current LectureWho discovers medicines in plantsEthnobotany- the study of indigenous plant useEthnobotanists study how a culture uses of plants for medicine, hunting, shelter, food, etc.…Shamans, Healers, Elders, Chiefs, etc.…They immerse themselves in a culture for extended periods of timeHow are medicines from plants discovered?Whole plant or extract was used traditionally for the same purpose as it is used now. Scientists have since isolated the active ingredient. Often the chemical is modified to alter potency and/ornegative effectsExamples:Digitalis purpurea  Digoxin;Salix alba  Salicin / Salicylic acid  acetyl salicylic acid (aspirin),Papaver somniferum  Morphine, codeine  diacetylmorphine, oxycodone, many other drugsErythroxylum coca  Cocaine,Ephedra sinica  Ephedrine / Pseudophedrine,  amphetamines.Foxglove, Digitalis purpurea, had been used as part of a folk remedy for dropsy for centuries.18th Century European MedicineEdema (AKA Dropsy or congestive heart failure) is caused by a weakening of the heart.This results in fluid accumulation in the body, and is an excruciating way to die.These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.William Withering (1741 - 1799)“discovered” foxglove by systematically testing the components of herbal treatments for dropsy- One of the first systematic tests of a folk remedy (1785).Digoxin and digitoxin are two of the active compounds.These act by regulating the pulse and strengthening each contraction.Digoxin is still used today, and still extracted from Digitalis sp.014#1 – How are medicines from plants discovered?Whole plant was used historically for a different purpose / disease than it is now usedCinchona  QuinineMadagascar periwinkle  Vinblastine and VincristineQuinine and MalariaMalaria is a disease caused by a protozoan parasite, Plasmodium spp. The parasite is vectored by Anopheles mosquitoes.Malaria was (and is) a devastating disease of tropical and subtropical parts of the world but was also found in Europe in the 16th century.Spanish Jesuits in Peru had started a collection of plants and botanical medicines in the early 17th century.One of these botanical medicines was the bark of the quina-quina tree (later named Cinchona by Linnaeus).- Peruvians originally used this bark as a muscle relaxant for relief from shivering- The Jesuits took this bark and tried it against malaria and it had a remarkable effectQuinineAntipyretic (fever-reducing), Antimalarial, Analgesic (painkilling), Anti-inflammatory, A bitter tasteQuinine is bitter, and so was mixed with sugar (and gin) to make it more palatable. Hence the development of the “gin and tonic”, which was (and still is) gin and quinineMadagascar (Rosy) periwinkle, Catharanthus roseusUsed in traditional medicine in Africa as a treatment for diabetes.Scientists at the University of Western Ontario and at Eli Lilly Pharmaceuticals examined this in the 1950s, and found no evidence for an effect on diabetesHowever, chemicals found in leaf extracts reduced white blood cell production.Two compounds from the plant, vinblastine and vincristine are used as treatments for leukemia and other cancers.Vinblastine has become contentious, and is used as an example where indigenous knowledge was “pirated” by a pharmaceutical company, and turned into a drug without compensating indigenous peoples.#2 – How are medicines from plants discovered?Toxic or poisonous plants examined for medicinesStrychnos toxifera and others  CurareSweet clover  CoumadinDicumarol and Warfarin/CoumadinIn the 1920s, cattle began dying in Wisconsin from uncontrollable bleeding and internal hemorrhage. This was determined to be caused by eating moldy sweet clover.In the 1940s, University of Wisconsin researchers identified the compound as dicumarol (an anticoagulant).o A derivative of this compound that they created, coumadin, was commercialized as a rat poison.Starting in the later 1950s, coumadin has been used to prevent clotting in humans.#3 – How are medicines from plants discovered?Brute force techniques: Screening thousands or tens of thousands of plants for activity.Taxus brevifolia  TaxolTaxol / Pacific YewIn the 1960s, the National Cancer Institute had a program to systematically collect and screen plants for anticancer activity. The bark of the pacific yew, Taxus brevifolia, had activity against some cancer types.The bark of the pacific yew, Taxus brevifolia, had activity against some cancer types (specific chemical called Paclitaxel).Taxol was isolated from the bark, but it required large amounts of bark from a relatively rare tree to produce the compound, about 1 tree per dose.This became very controversial - Should we (nearly) eliminate a tree for a cancer cure?A related species, Taxus baccata, contains a similar (but not active) compound at higher levels and in needles.- Currently, Taxol is produced by cell culture in Germany and wild yews are no longer harvested.#4 – How are medicines from plants discovered?Ethnobotanists study indigenous uses of plants; plants used as medicines are particularly interesting.Bioprospecting and BiopiracyBioprospecting - searching for new plants or bioactive molecules. Either randomly (e.g. Taxol), or by using local knowledge (e.g. vinblastine, quinine).Biopiracy - Commercial use of “traditional knowledge” or genetic resources without compensation to the indigenous people(s) that “discovered” the plant and/or medicinal properties of a plant.One ApproachIn 1993, Merck (US pharmaceutical company) paid INBio (conservation organization in Costa Rica) $1.2 million for access to 10,000 plant samples. Merck also supplies training and equipment to INBio scientists.Merck could patent any product produced from these plants, but would have to share royaltieswith Costa Rica.Another approach: International Cooperative Biodiversity Groups (ICBG)Funded by National Institute of Health, National Science Foundation, US Department of Agriculture, Department of Energy,