Ancient Drugs: Did They Work? (2024) - PDF

Ancient Drugs: did they work? By the end of this lecture, you will be able to …  Describe how historians try to reconstruct ancient drug use.  Describe common natural drug sources.  Know the names of key drug innovators and their important texts.  Provide arguments for and against the reconstr...

Ancient Drugs: did they work? By the end of this lecture, you will be able to …  Describe how historians try to reconstruct ancient drug use.  Describe common natural drug sources.  Know the names of key drug innovators and their important texts.  Provide arguments for and against the reconstruction of ancient medicines.   We can measure the reduction in deaths caused by a particular disease.  We can measure the closure of hospitals such as TB facilities or mental hospitals. How do we  But these measures don’t capture all the effects of a drug on a society: measure the  For example, mental hospital closures only tell us ‘success’ of a that mental hospitals closed.  It doesn't tell us whether the quality of life of the drug? former patients improved or not.  It’s almost impossible to measure the effects of ancient drugs on populations because of confounding factors.   Modern anthropology has identified traditional practices in some cultures.  BUT we can’t authoritatively link that to ancient civilisations. How do we  Finding evidence that particular groups ritually know what bathed, or tattooed, or ingested clays, tells us very little about their ideas about medicine and health. ancient drugs  We know they HAD ideas about health and illness. were used, and  But unless they: why?  wrote them down, and  this has survived, and  we can understand them clearly,  we don’t really know what those ideas were. The Pozzino shipwreck cargo – ‘medicine chest’  Pozzino shipwreck (Tuscany) – nearly 2000 years old.  Discovered in 1974; excavated 1989-90.  Doctor’s chest, including numerous wooden and tin vials; some medical instruments as well.  X-rays of sealed container = five tablets, each about 4cm wide by 1cm thick.  Samples => zinc 75% - smithsonite (zinc carbonate) and hydrozincite (zinc hydroxycarbonate).  Also contained small amounts of animal and vegetal lipids, beeswax, pine resin, pollen grains and starch grains. The container and the zinc tablets Is it medicine? And if so, what sort?  Pliny and Dioscorides both describe how zinc compounds (calamine) used to treat eyes and skin complaints.  The Latin calamina = calamine, a mix of smithsonite and zinc silicate => calamine lotion today. Is it medicine? If so, what sort?  Were these tablets collyria? (tablets which could be dissolved into an eye salve)  Collyria are usually stamped and shaped slightly differently?  There is pine resin in the tablets – was it there to prevent microbial degradation?  Was the pine resin an active ingredient instead?  We have more questions than answers! 2015: ancient remedy proved effective against MRSA   Make an eyesalve against a wen: take equal amounts of cropleac and garlic, pound well together, take equal amounts of wine and oxgall, mix with the The original alliums, put this in a brass vessel, let stand for nine nights in the brass vessel, wring through a cloth and recipe clarify well, put in a horn and at night apply to the eye with a feather; the best medicine. – Bald’s Leechbook Bald’s Leechbook recipe  Scientists recreated a 9th Century Anglo-Saxon remedy using onion, garlic and part of a cow's stomach.  This successfully and repeatedly killed methicillin-resistant staphylococcus aureus (MRSA).  Equal amounts of garlic and another allium (onion or leek), finely chopped and crushed in a mortar for two minutes.  Add 25ml (0.87 fl oz) of English wine - taken from a historic vineyard near Glastonbury.  Dissolve ox gall (bovine salts) in distilled water, add and then keep chilled for nine days at 4C.   The recipe only worked against MRSA when it was followed exactly: Following the  You needed the right combination of ingredients  The right preparatory method recipe!  The right waiting time  Changing any of these reduced its efficacy against staphylococcus. Weights and measures  If we want to test ancient drug formulas, we need to understand their weights and measures.  Unfortunately, these have varied considerably over time.  Roman system persisted into Europe.  Lots of local variations on these for centuries.  In 1864, UK legislation standardised the 'apothecaries' weights' - minims, scruples, grains, dra(ch)ms, ounces and pounds.  1963: metric system introduced to the British Pharmacopoeia.  1965: Australian pharmaceutical industry.  1971: United States pharmaceutical industry.  Micrograms (µg), milligrams (mg), grams (g), kilograms (kg) - millilitres, litres What do we really know about ancient use of medicinal drugs?  It’s a bit of a mixed bag – lots of guesswork.  Easy to credit a culture with ‘advanced’ knowledge of medicine through chance use of particular drugs.  Do you need to know how something works to use it effectively?  YES!  Don’t try ancient drug recipes at home – quantities unreliable, potencies unknown, often highly toxic ingredients! Plant sources (eTute 2 - Bioprospecting)  Leaves: tobacco, hemp, geranium, lavender, mint  Gums, sap, resins: aloe, balsam  Roots: ginger, galangal, turmeric, valerian, echinacea, liquorice  Bulbs: lotus bulb, autumn crocus (colchicine)  Flowers: chamomile, calendula  Seed-heads: hemp, poppy  Spices (dried plant parts): pepper, cinnamon, nutmeg, cloves, cumin   hemp plant – leaves and buds  opium poppy – seed-head Psychoactive /  coca leaves - chewed CNS  betel nut - chewed stimulating  kava leaves - chewed plants  tobacco – smoked or chewed  peyote - a cactus which produces mescalin  mushrooms - psilocybin   Clay – kaolinite  Chalk  Red ochre – iron salts? Mineral  Mercury  Arsenic sources  Metal containers, e.g. bronze  Verdigris – copper carbonate – artists’ pigment  Gold, silver, antimony, zinc Alcohol as medicine  Beer - universal drink  Wine or vinegar: hugely common as medicine - Hippocratic Corpus, Galen, Celsus  Roger Bacon (c.1214-1294) The Cure of Old Age, and Preservation of Youth - healing properties of wine.  Distilled spirits – not until after around 1 st century CE.  Antiseptic and anaesthetic properties. Ancient Nubian beer as medicine?  In 1980 anthropologists discovered what seemed to be the antibiotic tetracycline in nearly 2,000-year-old Nubian bones.  Did it come from their beer recipes?  Beer (as in Ancient Egypt) was made from bread.  Sprouted grains were milled into flour – soil bacterial Streptomyces could have entered process.  Nubian brewers made bread with tough outer crust and raw interior.  This was mixed with water and unmilled grains, and fermented into beer – full of tetracycline produced by Streptomyces.  Is this really ‘antibiotic’ use? We don’t know. Other sources  Raw honey  Insects – blister beetle = cantharides; spiders; ants; locusts  Animal organs and tissues – ox gall (bile salts); hair, horns, dung  Human body parts – hair, urine, blood, fat  Mummies – powdered for asphalt and ingested in medicines – artist’s pigment  Manuscripts – spells written on slips of paper and swallowed Ancient Egypt  The Ebers Papyrus:  Longest and most famous of the ancient Egyptian medical papyrii.  Contains herbal and magical remedies for common complaints.  Most of its ‘medical’ treatments are based on purging.  Body contains toxins that cause illness, which need to be expelled from the body. Ebers Papyrus – spell and ointment for leucoma (opacity in cornea). Gall was used to treat trachoma for at least two millennia. Gall is an irritant and cauterising agent. Shamanism  Ancient Egyptian medicine fits the pattern of shamanism.  Amulets, sacrifice, augury/prophecy, divination, cursing, advice, teaching, trances, communication with animals or the dead.  Common global practice.  Combined role of spiritual and physical healer.  Could be male or female.  Bridge between spirit world and physical world.  For reducing plentiful urine – proportions, but not actual measures: Transliteration and recipe – Ebers Papyrus Hippocratic Corpus – ulcer dressing recipe An ulcer dressing:-  The dried gall of an ox, the finest honey, white wine, in which the shavings of the lotus have been boiled, frankincense, of myrrh an equal part, of saffron an equal part, the flowers of copper, in like manner of liquids, the greatest proportion of wine, next of honey, and least of the gall.  Another:-Wine, a little cedar honey, of dried things, the flowers of copper, myrrh, dried pomegranate rind.  Another:-Of the roasted flowers of copper half a drachm, of myrrh two half-drachms, of saffron three drachms, of honey a small quantity, to be boiled with wine.  Gall and wine are both astringent.  Raw honey is antiseptic.  Copper salt preparations stimulate wound healing through the production of collagen and elastin.  Pedanius Dioscorides (40-90 CE):  Author of De Materia Medica, the first authoritative Western pharmacoepia (c.50-70 CE).  Hugely influential throughout Europe until 19th Ancient Rome - century. Dioscorides  Describes about 600 plants – not all can be identified even now.  Also includes animal products and minerals.  Still contains some magical uses for plants, eg. talisman against snakes. Dioscorides, ‘Roots’ (Book 3 of De Materia Medica)  POTERION  a large shrub with long branches — soft, flexible like a bridle, thin, similar to tragacanth — the leaves little, round. The whole shrub is surrounded with a thin woolly down and is prickly; the flowers are small and white. The seed (to one who tastes it) has a sweet scent and is sharp with no use. It grows in sandy and hilly countries. The roots are underneath, two or three feet long, strong and sinewy. When cut close to the ground they send out a fluid similar to gum. The roots (cut and smeared on) heal cut-apart sinews and wounds, and a decoction of it (taken as a drink) is good for disorders of the strength. It is also called phrynion, or andidotum, and the Ionians call it neurada.  Astragalus poterium, Astragalus arnacantha, Astragalus gummifer — Small Goat’s Thorn?  Positive effects of tragacanth on wound healing were demonstrated in 1 small clinical trial.  Clinical trial data are lacking to recommend use for any indication.  Galen of Pergamon (129-216 CE):  Influence extended well into the 1600s in Europe.  Is likely to be the author of most of the works attributed to him (over 500).  Two-part treatise De Compositione Roman Medicamentorum (On the Composition of Drugs). medicine -  Strongly influenced by Hippocratic approach and humoral theory. Galen  Carefully noted the exact measurements of drugs that he gave to patients.  BUT: Also believed in theriac – a mystery substance with 64 ingredients which could cure any illness in human beings.   Islamic world preserved Greek manuscripts from decline of Rome to early 1200s CE.  Heavily influenced by classical ideas – Greek, Roman - of medicine and herbalism.  Humoral theory underpinned Islamic approach to drug therapy. Classical Islam  Al-Rhazi (864-930 CE) – wrote extensively on diseases and treatments.  Introduced mercury-based compounds to pharmacopeia.  Ibn Sina (Avicenna) (980-1037 CE) – his book Al Qanun contains more than 700 drug preparations.  The Canon of Medicine (Al Qanun fit-Tibb) ‫‘( القانون في الطب‬law in medicine’)  To help produce breast-milk:  Eat the udders of sheep and goats [sympathetic magic].  An ounce of tree-worms or dried earthworms in barley water, drunk for several days.  Juices from the heads of salted fish, taken in water with dill.  Sesame, ground up and mixed with wine.  Dill seed (3 oz), seed of blue melilot (1 oz), leeks (1 oz), clover seed (1 oz), fennel seed (1 oz) – mix into a drink with fennel juice, honey, and butter. Earthworms are used as medicine in many Asian cultures. Dill is a purported galactagogue, but no scientifically valid clinical trials support this use. Fennel is still considered to be a natural galactagogue. Sesame seeds are also used traditionally as galactagogues. Paracelsus (1493-1541 CE)  Devoted mineralologist and toxicologist.  Challenged the theory-based approach to medicine.  Championed the use of mercury to treat syphilis.  BUT – believed in humoral theory, alchemy, the occult, astrology. Some Paracelsian remedies  For tuberculosis – eat the lungs of a fox [sympathetic magic]  Reported from Galen - a charm against epilepsy – hang a peony, that has been picked at an auspicious time, around your neck.  Against epilepsy: 6lb wine, 10 drams cantharides, flowers of tapsi, cannabis, chamomile, St Johns Wort, 6 hands-full. Crush and mix it together – allow it to draw in the rays of the sun or in the heat of manure for one month. Distill and add betony, resin, frankincense, earthworms. Distill for a further 8 days.  Cannabidiol has anticonvulsant properties.  Chamomile shows some anticonvulsant properties. The eighteenth century in Europe  1700s – flourishing new science of botany fuelled new drug experimentation.  More experimentation and better communication in medicine.  Folk remedies scrutinised more closely = digitalis treatment for heart conditions (Week 5).  BUT: humoral theory persisted!  Aspirin’s key ingredient is salicylic acid:  Isolated in 1800s from willow bark … Did ancient  … therefore, any ancient recipe mentioning willow must meant peoples use that this culture understood the pain-relieving properties of salicylic acid? aspirin?  Not true!   Effective drugs do exist in nature (like opioids, for example).  But it's usually in very tiny amounts - not therapeutic doses.  White willow bark (Salix alba) has quite a low concentration of salicin, compared to other Salix species. And why we  A standardised modern dose of 40-60mg of salicin would be very hard to obtain from simply chewing willow bark or drinking tea. know this  The tannins in the plant can be toxic at this dose.  Isolating salicin from willow bark came via modern experiments over quite a long time.  Making salicin into something useable – aspirin – took yet more time in modern pharmacological laboratories. So do ancient drugs work?  The short answer is: Some of them, sometimes.  The long answer is: We don’t really know because -  We usually can’t replicate the recipes - we don’t know the right quantities or ingredients.  We don’t know the right conditions under which to make the drug (shelf-life of ingredients, containers, other confounds).  It’s not always responsible to try if the ingredients are dangerous, e.g. mercury.  It takes time, patience, careful experimentation, and transparent reporting of results (including failures) to develop a drug recipe that works for most people, most of the time.  Most of these conditions could not be found in the ancient world! And is it worth it?  Even if we can replicate an ancient recipe:  they deteriorate over time and have very limited shelf-life.  they usually cannot be easily mass-produced.  they cannot be easily transported.  BUT: it’s fun and occasionally successful.  It might lead to new pathways in research for isolating effective trace elements. Next week …  Biological foundations – it’s human biology time!  Please ensure you complete eTute 1 next week, ideally before your lectures?  What happens to drugs in the body – Phil B  How drugs work in the body – Ricky C