Every tradition recorded plant medicines; isolating and testing a compound turned a few records into drugs

1. Mesopotamia: medical tablet from Nippur with prescriptions, c. 2200 BCE; Nineveh Medical Encyclopaedia, 7th century BCE, 50 tablets.
2. Egypt: Ebers Papyrus, end of the 16th century BCE, 879 texts.
3. Greece: Hippocratic Corpus, some 60 texts; Theophrastus (c. 371–287 BCE).
4. Rome: Dioscorides, De materia medica, about 77 CE, nearly 600 plants.
5. Persia: Ibn Sīnā's Canon of Medicine, begun about 1012; scholarship only.
6. India: Charaka and Sushruta compendia; Rauwolfia research leading to reserpine, 1952.
7. China: from 365 medicinals (Eastern Han) to 1,892 (Bencao Gangmu, 1578–1596).
8. Japan: Ishinpō, 984; 148 Kampo formulas reimbursed today.
9. Europe: willow, foxglove and poppy; morphine isolated 1805–1817.
10. West Africa: Calabar bean; physostigmine isolated 1864.
11. Madagascar: periwinkle; vinblastine and vincristine, 1950s.
12. Southern Africa: Pelargonium and Hoodia benefit-sharing cases.
13. North America: 44,691 recorded plant uses; mayapple and etoposide.
14. Andes: cinchona bark, c. 1630; quinine, 1820.
15. South America: curare; tubocurarine, 1935.
16. Brazil: jaborandi; pilocarpine, 1875.

Counts are the library's numbered ranges and categories. Leipzig University Library, Papyrus Ebers. The scroll's date (end of the 16th century BCE) rests on the calendar on its reverse and radiocarbon dating performed in 2014.

Japan: medical books on herbal drugs and acupuncture arrived from Wu in 562; exchange with China stopped in 894; Tamba Yasuyori presented the Ishinpō, the oldest extant medical book in Japan, to the emperor in 984. Kampo formulas were first covered by national health insurance in 1967, coverage expanded from 1976, and 148 formulas were covered by 1987, the number still listed.

1. 1969: Tu Youyou gathered over 2,000 herbal, animal and mineral prescriptions in three months and kept 640 in a brochure circulated in April 1969.
2. May 1969 to June 1971: water and ethanol extracts of over 100 herbs were tested in rodent malaria, with few promising results.
3. 1971: the team focused on qinghao. Ge Hong's handbook (East Jin dynasty, about 317–420) first records qinghao for periodic fevers; it led to a lower extraction temperature.
4. September 1971: extraction with ethyl ether at reduced temperature; an alkaline wash removed the acidic portion.
5. October 4, 1971: sample 191, the neutral portion, was fully effective in rodent malaria; monkey tests followed from December 1971 to January 1972.
6. August to October 1972: the extract was tested in 30 patients, 21 in Hainan and 9 in Beijing. Silica-gel separation followed, and artemisinin was isolated in November 1972.
7. April 27, 1973: the formula C₁₅H₂₂O₅ was established; the X-ray stereostructure was published in 1977.
8. Approvals: artemisinin in China in 1986, dihydroartemisinin in 1992; FDA approved Coartem (artemether–lumefantrine) in 2009. In 2015 Tu Youyou received one half of the Nobel Prize in Physiology or Medicine "for her discoveries concerning a novel therapy against Malaria".

Charaka: Britannica says he lived between the 2nd century BCE and the 2nd century CE, and estimates the Charaka-samhita in its present form at about the 1st century CE. Sushruta: Britannica says he flourished c. 6th century BCE; the Suśruta Project describes the Suśruta-samhita as composed in Sanskrit about two millennia ago.

Sarpagandha to reserpine: Sen and Bose reported Rauwolfia root for insanity and high blood pressure in 1931; Siddiqui and Siddiqui published the ajmaline series of alkaloids in 1932; Vakil's 1949 British Heart Journal paper brought Rauwolfia in hypertension to Western attention; Müller, Schlittler and Bein at CIBA isolated reserpine in pure crystalline form in 1952; the 1957 Lasker awards recognized reserpine and chlorpromazine in psychiatry, and Vakil.

1. Hippocratic Corpus, late 5th and 4th century BCE: some 60 texts by several authors; pharmakon usually meant a purgative.
2. Theophrastus (c. 371–287 BCE), Aristotle's pupil: Inquiry into Plants in nine books and Growth of Plants in six.
3. Dioscorides, De materia medica, about 77 CE: five books, nearly 600 plants, about 1,000 simple drugs. Pliny the Elder (23–79 CE) wrote the Natural History in 37 books.
4. Galen of Pergamum (129–c. 216): dominant in European medicine until the mid-17th century; his authority was similarly long-lived in the Byzantine world and the Muslim Middle East.
5. Vienna Dioscurides, early 6th century: an illustrated copy made for Juliana Anicia, restored in 1406, inscribed in the Memory of the World Register in 1997.
6. al-Rāzī (c. 854/865–925) and Ibn Sīnā, whose Canon was begun about 1012; Gerard of Cremona translated the Canon into Latin in Toledo in the 12th century; the Articella was taught at Salerno, Montpellier, Bologna and Paris up to the 17th century, and an Arabic Canon was printed in Rome in 1593.

• Calabar bean (Physostigma venenosum): missionaries who arrived in Old Calabar in 1846 documented the ordeal bean; Christison tested a bean on himself in 1855; Balfour named the plant about six years later; Argyll Robertson showed in 1863 that the extract constricts the pupil. Physostigmine was isolated in 1864, its structure was known by 1923, and it has been used for glaucoma and myasthenia gravis.
• Madagascar periwinkle (Catharanthus roseus): leaf extracts were reputed to help in diabetes. Testing that claim, Noble and Beer found the anticancer alkaloids vinblastine and vincristine in the 1950s.
• Pelargonium sidoides: a Southern African traditional medicine sold in Europe as Stevens' Cure and later Umckaloabo, with 18 clinical studies by 2008, mainly in acute bronchitis. Patents on extracts of P. sidoides and P. reniforme were granted in 2003 and 2005 without a benefit-sharing agreement, according to the African Centre for Biosafety.
• Hoodia gordonii: also used by the Khoisan. CSIR patented P57 in 1995 and licensed it six years later; a 2003 agreement gives the San a 6% share of CSIR's financial benefits from its partners. A 15-day trial of a purified extract found no effect on energy intake or body weight.

• Cinchona bark: Jesuit missionaries in South America used it against fevers about 1630, and a legend credits earlier Indigenous use. Pelletier and Caventou isolated and named quinine in 1820, and purified quinine replaced the bark. Achan and colleagues describe quinine as the first successful use of a chemical compound against an infectious disease.
• Curare: explorers described South American arrow poisons in the 16th century; Claude Bernard located their site of action in the mid-19th century; King isolated tubocurarine in 1935; neuromuscular blockers became established as muscle relaxants in surgery after 1943.
• Jaborandi (Pilocarpus): Symphronio Coutinho took the leaves to Europe in 1873; Hardy and Gerrard independently discovered pilocarpine in 1875; Weber introduced it as a pupil-constricting eye drug in 1876.

Mayapple (Podophyllum peltatum): 39 records from Iroquois (13), Cherokee (12), Meskwaki (5), Delaware, Oklahoma (3), Menominee (3), Delaware (2) and Chippewa (1); 25 drug, 11 food and 3 other records. Earlier editions: 4,869 items (1977) and 17,634 medicinal items from 123 groups (1986).

• Isolated and used as found: morphine from opium poppy (Sertürner, reported 1805, full account 1817), described as the first alkaloid isolated from any plant; digoxin from woolly foxglove, Digitalis lanata (Sydney Smith, 1930), after Withering's 1785 account of the foxglove; galantamine from snowdrop, developed from Caucasian observations and Bulgarian use and approved by FDA for Alzheimer's disease on February 28, 2001.
• Chemically modified: salicin purified from willow bark (1829), then pure acetylsalicylic acid made at Bayer (1897); podophyllotoxin from mayapple, modified into etoposide (FDA, November 10, 1983), which inhibits topoisomerase II where podophyllotoxin binds tubulin; artemisinin modified into artemether, the partner of lumefantrine in Coartem (FDA, April 7, 2009).

The 31.4% share of S* and S*/NM is computed here from the abstract's counts (58 of 185). The NB share is as reproduced in Sarbadhikary P, George BP. Plants 2022;11:2293.

• Passed all four (recorded use, compound isolated, medicine, matching use): qinghao to artemisinin, cinchona to quinine, willow to aspirin.
• Medicine with a different use from the tradition: Calabar bean to physostigmine (recorded as an ordeal poison), periwinkle to vinca alkaloids (tested as antidiabetic, anticancer activity found).
• Medicine without a clear traditional use: jaborandi to pilocarpine (Indigenous use could not be pinned down), Pacific yew to paclitaxel (found by plant screening).
• Medicine from a related synthetic: goat's rue to metformin (guanidine lowered blood glucose in 1918; metformin is synthetic).
• No medicine: Hoodia (a 15-day trial of a purified extract found no effect on energy intake or body weight) and Aristolochia (aristolochic acids are listed as known human carcinogens).

• June 5, 1992: the Convention on Biological Diversity opens for signature at Rio. June 4, 1993: the United States signs; it has not become a Party. December 29, 1993: the Convention enters into force.
• 1995: CSIR patents P57 from Hoodia; 2001: licence to Phytopharm; 2003: benefit-sharing agreement with the San. 2003 and 2005: patents on Pelargonium extracts, with no benefit-sharing agreement according to the African Centre for Biosafety.
• October 29, 2010: the Nagoya Protocol is adopted; October 12, 2014: it enters into force; October 2026: 143 Parties.
• May 24, 2024: WIPO adopts a treaty requiring patent applicants to disclose the country of origin of genetic resources, or the Indigenous Peoples or local community that provided associated traditional knowledge, when a claimed invention is based on them.