Science: Where the Drugs Came From

From

Penicillium mold Penicillium rubens (long recorded as P. notatum)

When

1928, made usable 1940 to 1945

Who

Alexander Fleming; then Howard Florey, Ernst Chain and Norman Heatley

Fleming returned from holiday to a stack of staphylococcus plates, one contaminated by a mold that had cleared a ring in the bacterial lawn around itself. He identified the mold and published, then largely moved on: the active substance was unstable and he could not concentrate it. Ten years later an Oxford group led by Florey and Chain, with Heatley building the extraction apparatus out of bedpans and milk churns, produced enough to treat a patient. The first man they treated recovered while the supply lasted and died when it ran out, so they began recovering the drug from patients' urine to re-dose them.

Used now for: Streptococcal and pneumococcal infection, syphilis, and as the parent of the amoxicillins, cephalosporins and carbapenems

From

A mold first studied for what it did to plants Penicillium griseofulvum

When

1939, in medical use from 1958

Who

Percival Oxford, Harold Raistrick and Percy Simonart

The compound was isolated as a curiosity that stunted fungal growth and made hyphae curl. Plant pathologists used it against fungal disease in crops for years before anyone tried it on a person's scalp. It works by binding to fungal microtubules and it collects in keratin, which is why it treats hair and nail infection from the inside.

Used now for: Ringworm of the scalp and nail infection, mostly in children

From

A soil fungus from a Norwegian plateau Tolypocladium inflatum

When

1970, transplant use from 1978

Who

Hans Peter Frey collected the soil; Jean-Francois Borel showed what it did

Sandoz asked staff on holiday to bring back soil samples. One bag came from the Hardangervidda plateau in Norway, and the fungus in it produced a compound that suppressed lymphocytes without the general marrow poisoning of the drugs then used. Borel kept the project alive inside the company when it looked commercially hopeless, and later drank a dose himself to settle an argument about absorption. Organ transplantation changed from an experiment into a routine operation within a decade of its arrival.

Used now for: Kidney, liver and heart transplantation, severe psoriasis and uveitis

From

Blue-green mold, then a soil fungus and a red rice mold Penicillium citrinum, then Aspergillus terreus and Monascus ruber

When

1971 to 1976, first approval 1987

Who

Akira Endo

Endo reasoned that a fungus competing with other organisms might attack the cholesterol pathway that they need for their cell membranes, so he screened thousands of broths for exactly that. The hit came from Penicillium citrinum and was named compactin. Development in Japan stalled on a toxicity scare, and Merck, working with Endo's published route, brought lovastatin from Aspergillus terreus to market. Monascus, the same mold that colors red yeast rice, makes the identical compound, which is why that food supplement and the drug are chemically continuous.

Used now for: Lowering LDL cholesterol and reducing cardiovascular events

In Chinese medicine: Hong Qu, red yeast rice, is fermented with Monascus

From

A fungus that infects rye Claviceps purpurea

When

Midwives used it for centuries; ergotamine isolated 1918

Who

Arthur Stoll at Sandoz; later Albert Hofmann

Eating bread made from infected rye caused epidemics of burning limbs and gangrene known as St Anthony's fire, and the same fungus was used deliberately by midwives to contract the uterus after birth. Stoll isolated ergotamine, and Hofmann spent years making derivatives from the shared lysergic acid core, one of which was ergometrine for postpartum bleeding and another, the twenty-fifth in the series, was LSD. Bromocriptine came from the same chemistry and became a dopamine agonist for Parkinson's disease and prolactin-secreting tumors.

Used now for: Migraine, postpartum hemorrhage, Parkinson's disease and hyperprolactinaemia

From

A soil bacterium, one strain from a chicken's throat Streptomyces griseus

When

1943

Who

Albert Schatz, in Selman Waksman's laboratory

Waksman's laboratory screened soil organisms systematically for antibacterial activity, an approach he named antibiosis. Schatz, then a graduate student, found streptomycin in two strains and it did what penicillin could not: it killed the tuberculosis bacillus. It was the first effective TB drug, and the trials that established it also established the modern randomized trial. Waksman alone received the Nobel Prize, and Schatz spent decades contesting the credit.

Used now for: Tuberculosis, plague and tularaemia; the class includes gentamicin and amikacin

From

A golden soil bacterium from a Missouri field Streptomyces aureofaciens

When

1945, published 1948

Who

Benjamin Duggar, at Lederle after mandatory retirement from academia

Duggar was 72 and had been forced to retire when he took a job screening soils. The organism he found produced a gold-colored antibiotic, chlortetracycline, that worked against a wider range of bacteria than anything then available and could be swallowed instead of injected. Doxycycline and minocycline are later semisynthetic members of the same family.

Used now for: Acne, chlamydia, rickettsial infection, Lyme disease and malaria prophylaxis

From

Soil from a Philippine garden Saccharopolyspora erythraea

When

1949, marketed 1952

Who

Abelardo Aguilar, a physician in Iloilo, who sent the sample to Eli Lilly

Aguilar mailed a soil sample to his employer, Eli Lilly, which isolated the organism and the antibiotic. The drug became the standard alternative for people allergic to penicillin. Aguilar received no royalties, and Philippine campaigns to recognize him continued after his death. Azithromycin and clarithromycin are derivatives of the same molecule.

Used now for: Respiratory and skin infection, whooping cough, and as the parent of azithromycin

From

Soil from the interior of Borneo, sent by a missionary Amycolatopsis orientalis

When

1953

Who

Edmund Kornfeld at Eli Lilly

A missionary friend of a Lilly chemist sent back a soil sample from Borneo. The compound in it killed staphylococci that had already learned to resist penicillin, and early impure preparations were brown enough that the team called the material Mississippi mud. It was held in reserve for decades and became the drug of last resort for resistant staphylococcus, which is why resistance to it is watched so closely.

Used now for: MRSA, resistant enterococcal infection and Clostridioides difficile colitis

From

Soil from the Orinoco river valley Streptomyces nodosus

When

1955

Who

Walter Gold, Hugh Stout, John Pagano and Raymond Donovick at Squibb

The organism came from a soil sample taken in Venezuela. The drug binds ergosterol in fungal membranes and punches holes in them, which works against fungi that nothing else touched. Its toxicity earned it the nickname amphoterrible among physicians, and reformulating it inside lipid particles decades later was an attempt to keep the killing and lose the kidney damage.

Used now for: Life-threatening systemic fungal infection and visceral leishmaniasis

From

Soil from the grounds of a thirteenth-century castle in Puglia Streptomyces peucetius

When

1963, doxorubicin 1969

Who

Federico Arcamone and colleagues at Farmitalia, with Aurelio Di Marco

The soil came from around Castel del Monte in southern Italy, and the red pigment the organism made turned out to kill dividing cells by jamming DNA repair. Daunorubicin worked but damaged the heart, so the team mutated the organism and screened its output until they had doxorubicin, which was more active and remains one of the most used cancer drugs in the world. The cumulative heart damage is still the limit on how much of it a person can ever receive.

Used now for: Breast cancer, lymphoma, sarcoma and childhood leukemia

From

A soil bacterium from a Japanese mine Streptomyces verticillus

When

1962

Who

Hamao Umezawa

Umezawa screened soil organisms for anticancer activity, not for antibacterial activity, which was an unusual question to ask at the time. Bleomycin cuts DNA using a bound iron atom and, unlike most chemotherapy, spares the bone marrow. It is a component of the regimen that made testicular cancer one of the most curable solid tumors, at the cost of a risk of lung scarring.

Used now for: Testicular cancer, Hodgkin lymphoma and as a sclerosant for malformations

From

Soil from Easter Island Streptomyces hygroscopicus

When

1972

Who

Suren Sehgal at Ayerst, from a 1964 expedition sample

The sample came from Rapa Nui, which is why the compound is called rapamycin. It was found as an antifungal, then abandoned when the company closed the laboratory; Sehgal took a vial home and kept it in his freezer for years until the project could be restarted. It turned out to inhibit a growth-regulating protein complex that was named after it, mTOR, and became a transplant drug, a coating for cardiac stents, a cancer drug and the most studied molecule in the biology of ageing.

Used now for: Transplant immune suppression, drug-eluting stents, some cancers and tuberous sclerosis

From

The bacterium behind sausage poisoning Clostridium botulinum

When

Described 1820s, therapeutic use from 1977

Who

Justinus Kerner described the poisoning; Alan Scott made it a treatment

Kerner, a district health officer and poet, worked out in the 1820s that badly preserved sausage contained a substance that paralysed muscle, and suggested it might one day treat conditions of excessive movement. He was right by 150 years. Scott, an ophthalmologist, injected tiny purified doses into eye muscles to correct squint, and the cosmetic use was noticed afterwards as a side effect that patients liked.

Used now for: Squint, dystonia, spasticity, chronic migraine and cosmetic use

From

Willow bark, and meadowsweet Salix species; Filipendula ulmaria, formerly Spiraea

When

1763 trial, salicin isolated 1828, acetylated 1897

Who

Edward Stone; Johann Buchner; Felix Hoffmann and Arthur Eichengrun at Bayer

Willow bark for fever is recorded from Sumerian tablets onward, but Stone, an English clergyman, ran something close to a trial: he dried the bark, dosed fifty people with ague and wrote up the results for the Royal Society in 1763. Buchner isolated salicin in 1828, and salicylic acid worked but wrecked the stomach. Hoffmann acetylated it at Bayer in 1897 to make a tolerable version, and the name aspirin keeps a fragment of Spiraea, the meadowsweet genus that was the other source of the acid. How it works was only explained in 1971, when John Vane showed it blocks prostaglandin synthesis.

Used now for: Pain, fever, and lifelong low-dose use to prevent clotting after a heart attack or stroke

From

Opium poppy latex Papaver somniferum

When

1804 to 1805

Who

Friedrich Sertuerner, an apprentice apothecary in Paderborn

Opium was ancient, but its strength varied so wildly between batches that dosing was guesswork. Sertuerner, in his twenties and working alone, precipitated a crystalline base from it, tested it on stray dogs and then on himself and three friends, and nearly killed all four. He had isolated the first plant alkaloid, and named it after Morpheus. That single result created the idea that a plant's activity lives in a specific compound that can be weighed, which is the foundation of pharmacology. Codeine followed in 1832 and papaverine in 1848, and naloxone, the overdose antidote, is a later modification of the same skeleton.

Used now for: Severe pain, cough suppression, and the reference against which all analgesia is measured

In Chinese medicine: Ying Su Ke, the poppy husk, used for chronic cough and diarrhoea · read the herb page

From

Cinchona bark from the Andes Cinchona officinalis and related species

When

In Europe from the 1630s, isolated 1820

Who

Pierre Joseph Pelletier and Joseph Bienaime Caventou

Quechua people used cinchona bark, and Jesuit missionaries carried it to Europe, where it was sold as Jesuit's bark and distrusted for exactly that reason. Pelletier and Caventou isolated quinine in 1820, which made reliable dosing possible and, with it, European campaigns in malarial regions. The bark's other alkaloid, quinidine, became a heart drug after a Dutch merchant told the cardiologist Karel Wenckebach that he could stop his own attacks of atrial fibrillation with quinine, and was believed. Chloroquine and mefloquine are synthetic descendants of the same chemistry.

Used now for: Severe malaria; quinidine for certain arrhythmias

From

Sweet wormwood Artemisia annua

When

1972

Who

Tu Youyou and the Project 523 team

Project 523 was a wartime assignment to find a malaria drug for troops in Vietnam, and Tu's group screened hundreds of traditional preparations with poor results. She went back to the texts and found in Ge Hong's fourth-century handbook of emergency prescriptions that the herb was to be soaked and wrung out, not boiled, which suggested the active compound was heat-sensitive. A cold ether extraction gave complete clearance of parasites in animals, and the team took the first human doses themselves. Tu received the Nobel Prize in 2015, and artemisinin combinations are now the first-line treatment for falciparum malaria worldwide.

Used now for: Falciparum malaria, always in combination to slow resistance

In Chinese medicine: Qing Hao, sweet wormwood, classically used for alternating chills and fever

From

Foxglove Digitalis purpurea and D. lanata

When

1775 to 1785

Who

William Withering, from a Shropshire herbalist's recipe

Withering heard of a family recipe for dropsy, the fluid overload of heart failure, kept by a woman in Shropshire. He worked out which of its twenty-odd ingredients mattered, settled on foxglove leaf, and then spent ten years recording 163 cases with the dose, the timing and the failures included. His account of the narrow line between the useful dose and the toxic one is still the standard description of the drug. The specific glycoside now used, digoxin, is drawn mainly from the woolly foxglove.

Used now for: Rate control in atrial fibrillation and some heart failure

From

Pacific yew bark, then European yew needles Taxus brevifolia, then Taxus baccata

When

Collected 1962, structure 1971, approved 1992

Who

Arthur Barclay collected the bark; Monroe Wall and Mansukh Wani found the compound

Barclay, a botanist on a US government plant-screening program, stripped bark from yews in a Washington forest and sent it in with hundreds of other samples. Wall and Wani traced the activity and published the structure, and it took another twenty years to understand that it works by freezing microtubules instead of breaking them, and to solve the supply problem: treating one patient took several mature trees, and the trees grow slowly in old forest. The answer was to take a precursor from the fast-growing needles of the European yew and finish the molecule chemically, which is how it is still made.

Used now for: Ovarian, breast, lung and pancreatic cancer, and on coronary stents

From

The happy tree of southern China Camptotheca acuminata

When

1966

Who

Monroe Wall and Mansukh Wani

The same two chemists who solved paclitaxel isolated camptothecin from a Chinese ornamental tree. The parent compound failed in early trials because it was insoluble and unpredictably toxic, and the program was dropped for over a decade. It was revived once the target was identified as topoisomerase I, and water-soluble analogues built around the same core became standard drugs. Irinotecan is now part of the main regimens for advanced bowel cancer.

Used now for: Colorectal, small-cell lung and ovarian cancer

In Chinese medicine: Xi Shu, recorded in Chinese materia medica

From

Mayapple root Podophyllum peltatum and P. hexandrum

When

Podophyllotoxin known from 1880, etoposide 1966

Who

Sandoz chemists, from a resin long used by Penobscot people and North American physicians

The resin of mayapple root was used by Penobscot people and later listed in American pharmacopoeias as a purgative and a treatment for warts. Podophyllotoxin, its active constituent, poisoned dividing cells but was far too toxic to give internally. Semisynthetic modification produced etoposide, which acts on a different target from its parent and is gentle enough to be one of the most widely used cancer drugs.

Used now for: Small-cell lung cancer, testicular cancer, lymphoma and leukemia

From

Madagascar periwinkle Catharanthus roseus

When

1958

Who

Robert Noble and Charles Beer in Ontario; Gordon Svoboda at Eli Lilly

Noble's brother sent him leaves of a plant used in Jamaica as a folk remedy for diabetes. It did nothing to blood sugar, but injected extracts dropped the white cell count in rats and killed them of infection, which is the opposite of a failure if you are looking for a leukemia drug. Two closely related alkaloids came out of the work: vinblastine for Hodgkin lymphoma and vincristine, which turned childhood acute lymphoblastic leukemia from a death sentence into a disease most children survive.

Used now for: Childhood leukemia, Hodgkin lymphoma and several solid tumors

From

Autumn crocus, or meadow saffron Colchicum autumnale

When

Described in antiquity, isolated 1820

Who

Pelletier and Caventou again

The plant is named for Colchis on the Black Sea, and Dioscorides warned it was poisonous while physicians used it for joint pain anyway. Isolation in 1820 allowed dosing that treated gout without killing the patient, though the margin remains narrow. Its mechanism, binding tubulin and blocking the movement of inflammatory cells, later made it useful in conditions that have nothing to do with gout, including familial Mediterranean fever, pericarditis and coronary inflammation.

Used now for: Acute gout, familial Mediterranean fever, pericarditis and secondary cardiovascular prevention

From

Deadly nightshade, henbane and thorn apple Atropa belladonna, Hyoscyamus niger, Datura stramonium

When

Atropine isolated 1831

Who

Heinrich Mein; the eye effect was known long before

Belladonna means beautiful lady, and the name records the cosmetic use of the juice to widen the pupils. The same plants were poisons, anesthetics of a dangerous kind, and ingredients in the ointments described in witchcraft trials. Once atropine was isolated it became an ophthalmic tool, a treatment for slow heart rate, a drying agent before anesthesia, and the antidote to nerve agents and organophosphate pesticides. Hyoscine from henbane is still the standard drug for motion sickness.

Used now for: Bradycardia, organophosphate poisoning, pupil dilation and motion sickness

From

Calabar bean, an ordeal poison Physostigma venenosum

When

1864

Who

Jobst and Hesse isolated it; Robert Christison tested it on himself

In parts of West Africa the bean was used in trial by ordeal: the accused swallowed it, and survival was taken as innocence. Christison, in Edinburgh, ate a portion to characterise the poisoning and only survived by drinking his shaving water to make himself vomit. Understanding that it blocks the breakdown of acetylcholine gave medicine a whole class of drugs: glaucoma drops, the reversal agents used at the end of every general anesthetic, and the mainstay treatment for myasthenia gravis.

Used now for: Myasthenia gravis, reversal of neuromuscular blockade and glaucoma

From

Amazonian arrow poison Chondrodendron tomentosum and Strychnos species

When

Studied from 1800s, surgical use 1942

Who

Claude Bernard explained it; Harold Griffith used it in surgery

Indigenous hunters in the Amazon prepared curare so that struck animals stopped breathing while the meat stayed edible, which tells you the poison acts on nerve endings and is not absorbed from the gut. Bernard showed it blocks the junction between nerve and muscle, leaving both intact. In 1942 Griffith and Enid Johnson in Montreal gave it during an appendicectomy, which meant a surgeon could have a relaxed abdomen without pushing anesthesia to a dangerous depth. Every modern paralytic used in surgery and intensive care descends from that afternoon.

Used now for: Muscle relaxation for surgery and ventilation, now with synthetic agents

From

Indian snakeroot Rauvolfia serpentina

When

1952

Who

Emil Schlittler and colleagues at Ciba

Sarpagandha root had been used in India for centuries for insomnia, agitation and what the texts call insanity, and Indian physicians reported in the 1930s that it lowered blood pressure. Ciba isolated reserpine in 1952. It became one of the first drugs to control hypertension and one of the first to quiet psychosis, and it caused depression in a fraction of the people who took it. That side effect was the observation that launched the monoamine theory of depression, because reserpine depletes exactly the transmitters that later antidepressants raise.

Used now for: Rarely prescribed now, but foundational to psychopharmacology

From

Ma Huang, ephedra stem Ephedra sinica

When

1885, in Western medicine from 1924

Who

Nagai Nagayoshi isolated it; Ko Kuei Chen and Carl Schmidt introduced it in the West

Ma Huang is one of the oldest recorded Chinese herbs for wheezing and for driving out cold. Nagai, trained in Japan and Germany, isolated ephedrine in 1885, and forty years later Chen, working from his family's knowledge of the herb, characterised its actions with Schmidt at Peking Union Medical College and gave asthma medicine its first reliable bronchodilator. The molecule is also the template for amphetamine, and the herb's later career as a weight-loss supplement, banned in the United States in 2004 after deaths, is the clearest case on this site of a plant being safe as a prescribed medicine and dangerous as an unregulated product.

Used now for: Blood pressure support during anesthesia; pseudoephedrine as a decongestant

In Chinese medicine: Ma Huang, warm and acrid, classically for wind-cold with wheezing · read the herb page

From

Coca leaf Erythroxylum coca

When

Isolated 1860, surgical use 1884

Who

Albert Niemann isolated cocaine; Karl Koller made it an anesthetic

Coca leaf was chewed in the Andes for millennia and Niemann isolated cocaine in 1860, noting that it numbed his tongue. That note sat unused for twenty years until Koller, a young ophthalmologist in Vienna and a colleague of Freud's, realised that a numb surface meant eye surgery could be done on a conscious patient without pain. Surgery changed within months. The addictive parent drug was then engineered out: procaine arrived in 1905 and lidocaine, still the workhorse, in 1943.

Used now for: Every local and regional anesthetic, and lidocaine for arrhythmias

From

Tea leaves and coffee beans Camellia sinensis; Coffea arabica

When

Caffeine 1819, theophylline 1888

Who

Friedlieb Runge isolated caffeine; Albrecht Kossel isolated theophylline

Goethe suggested to Runge that he analyse coffee beans, and caffeine was the result. Kossel later isolated the closely related theophylline from tea. Theophylline relaxes airway muscle and was a mainstay of asthma treatment for most of the twentieth century, though its narrow safe range pushed it aside once inhalers arrived. Caffeine is still a drug in neonatal intensive care, where it is the standard treatment for the apnoea of prematurity.

Used now for: Apnoea of prematurity, and theophylline in some obstructive lung disease

From

Bishop's weed Ammi visnaga

When

Khellin isolated 1879, cromolyn 1965

Who

Roger Altounyan, who tested every candidate on his own asthma

Khella has been used in Egypt for renal colic since antiquity, and its constituent khellin relaxes smooth muscle. Altounyan, a physician with asthma, spent years inhaling candidate derivatives and then deliberately exposing himself to guinea pig hair to see whether an attack still came. The 670th compound worked, and became sodium cromoglicate. The same khellin chemistry, pursued for coronary dilation, produced amiodarone, which turned out to be a powerful antiarrhythmic.

Used now for: Allergic asthma and allergic eye disease; amiodarone for serious arrhythmias

From

Goat's rue, or French lilac Galega officinalis

When

Guanidine isolated 1918, clinical use 1957

Who

Jean Sterne named and introduced it

The plant was a folk remedy for excessive thirst and urination, which is a description of diabetes, and it is toxic to grazing sheep. Guanidine from the plant lowered blood sugar in animals in the 1910s, and the safer derivative metformin was made in the 1920s and then forgotten while insulin took the field. Sterne, in Paris, revived it in 1957 and called it Glucophage, the glucose eater. It is now the first drug offered for type 2 diabetes almost everywhere in the world.

Used now for: Type 2 diabetes, polycystic ovary syndrome and diabetes prevention

From

Snowdrop and daffodil bulbs Galanthus and Leucojum species

When

Isolated in the 1950s

Who

Soviet and Bulgarian pharmacologists, including Dimitar Paskov

The often-repeated account is of a Bulgarian pharmacologist noticing villagers rubbing snowdrop on the forehead for nerve pain, and while that story is hard to source, the Eastern European research on Galanthus alkaloids in the 1950s is well documented. Galantamine was used for polio-related paralysis and for reversing anesthesia before it was reintroduced in the 1990s for Alzheimer's disease. It both inhibits cholinesterase and modulates nicotinic receptors, which is unusual for the class.

Used now for: Mild to moderate Alzheimer's disease

From

Toothed clubmoss Huperzia serrata

When

Isolated 1948, characterised in the 1980s

Who

Chinese pharmacologists working from the herb Qian Ceng Ta

The clubmoss was used in China for bruising, swelling and fever. Its alkaloid turned out to be a potent and selective cholinesterase inhibitor, and it has been used in China as a drug for memory impairment while remaining a supplement and not an approved medicine in the United States and Europe. It is the clearest current example of a traditional herb sitting exactly on the line between the two regulatory worlds.

Used now for: Prescribed in China for memory impairment; studied elsewhere in Alzheimer's disease

In Chinese medicine: Qian Ceng Ta

From

Jaborandi leaves Pilocarpus jaborandi

When

1875

Who

Symphronio Coutinho brought the plant to Europe; Hardy and Gerrard isolated the alkaloid

Indigenous Brazilians used jaborandi leaves to provoke sweating and salivation, and a Brazilian physician carried the plant to Europe, where two chemists independently isolated pilocarpine in the same year. Dropped into the eye it constricts the pupil and lowers pressure, which made it the first useful glaucoma treatment. It is still given by mouth to restore saliva in people whose glands have been damaged by radiotherapy or Sjogren's syndrome.

Used now for: Glaucoma, dry mouth after radiotherapy, and presbyopia drops

From

Ipecac root Carapichea ipecacuanha

When

Isolated 1817

Who

Pelletier and Francois Magendie

Ipecac reached Europe from Brazil in the seventeenth century and was used to induce vomiting and to treat dysentery. Emetine, isolated in 1817, was the first drug that reliably killed the amoeba causing dysentery and it remained in use for over a century despite damaging the heart. Syrup of ipecac itself stayed in household medicine cabinets as an emetic for poisoning until that practice was abandoned as more harmful than helpful.

Used now for: Largely replaced by metronidazole, but historically the first amoebic dysentery cure

From

Mexican wild yam, and soybean sterols Dioscorea mexicana, barbasco root

When

1938 to 1951

Who

Russell Marker; Carl Djerassi, Luis Miramontes and George Rosenkranz at Syntex; Percy Julian

Steroid hormones were made from ox bile and animal glands in quantities so small they were worth more than gold. Marker worked out how to strip a yam sterol down to progesterone, could not interest any company, and drove into Mexico himself to collect barbasco root from local harvesters and found the company that became Syntex. Percy Julian, working around the same problem from soybean sterols, made the supply cheaper again. In 1951 Miramontes, a graduate student, synthesised norethindrone, the compound that made an oral contraceptive possible. Every steroid inhaler, cortisone injection and contraceptive pill runs back through this plant chemistry.

Used now for: Contraception, asthma inhalers, inflammatory disease and hormone replacement

In Chinese medicine: Huang Yao Zi, a Dioscorea used for goitre and swelling · read the herb page

From

Coptis, barberry and goldenseal Coptis chinensis; Berberis species

When

Isolated in the 1820s

Who

European chemists working on barberry root

Huang Lian is one of the bitterest and most used cold-clearing herbs in Chinese medicine, and berberine is the yellow alkaloid that gives it both color and name. It has been used as an antimicrobial and antidiarrhoeal for decades in China, and has been studied more recently for blood glucose and lipids. It is not an approved drug in the West, so it sits in the same regulatory gap as huperzine: a defined molecule with real activity, sold as a supplement.

Used now for: Used in China for infectious diarrhoea; studied for glucose and lipid control

In Chinese medicine: Huang Lian, bitter and cold, clears heat and dries damp · read the herb page

From

Stephania root Stephania tetrandra

When

Isolated in the 1930s

Who

Chinese and Japanese pharmacologists

Han Fang Ji is used in Chinese medicine for painful swollen joints and fluid retention, and tetrandrine from its root blocks calcium channels, which is why it lowers blood pressure. The herb also carries a hard lesson about identification: in the 1990s a Belgian weight-loss clinic dispensed capsules in which this root had been substituted with Aristolochia, whose aristolochic acid caused kidney failure and urinary tract cancer in over a hundred women. The molecule was never the problem. The label was.

Used now for: Studied for hypertension and silicosis in China; the substitution case reshaped herb regulation

In Chinese medicine: Han Fang Ji, for wind-damp painful obstruction · read the herb page

From

Nux vomica seeds Strychnos nux-vomica

When

Isolated 1818

Who

Pelletier and Caventou

The seeds were used as a stimulant and tonic in both Chinese and European practice, and the alkaloid was isolated in 1818 by the pair who also gave medicine quinine and colchicine. Strychnine was never a good medicine, and its lasting contribution is scientific: because it blocks glycine receptors in the spinal cord with great specificity, it became the tool that revealed how inhibition works in the central nervous system. It also gave Robert Robinson and Robert Woodward one of the classic structural puzzles of organic chemistry.

Used now for: Not therapeutic; a research tool and a historical poison

In Chinese medicine: Ma Qian Zi, used externally and in tiny processed doses · read the herb page

From

Senna leaves and pods Senna alexandrina

When

In Arab medicine by the ninth century

Who

Recorded by Arab physicians, standardized in the twentieth century

Senna entered medicine through Arabic pharmacology and never left it. The sennosides are inactive as swallowed and are converted by gut bacteria into the compound that stimulates the colon, which is why the effect arrives some hours later and why it depends on the microbiome. It is one of very few herbal preparations that remains a licensed medicine in its plant form instead of being replaced by a synthetic.

Used now for: Constipation, including opioid-related constipation, and bowel preparation

In Chinese medicine: Fan Xie Ye, purges accumulation

From

Chilli peppers Capsicum species

When

Isolated 1846, receptor identified 1997

Who

John Clough Thresh isolated it; David Julius identified its receptor

Capsaicin is what makes a chilli hot, and rubbing pepper preparations on aching joints is old folk practice. Julius used it as a probe to find the receptor it acts on, TRPV1, which turned out to be the sensor the body uses for damaging heat; that work shared the 2021 Nobel Prize. Applied repeatedly at high dose it exhausts and retracts the pain fibers it stimulates, which is why a substance that burns is used as a painkiller.

Used now for: Neuropathic pain, as a high-dose dermal patch and low-dose creams

From

Cannabis Cannabis sativa

When

CBD isolated 1940, structures solved 1963 to 1964

Who

Roger Adams isolated CBD; Raphael Mechoulam and Yechiel Gaoni solved both structures

Mechoulam obtained hashish from the Israeli police, separated the constituents, and showed which one was intoxicating and which was not. That distinction is the basis of the entire modern cannabinoid field, including the discovery of the body's own cannabinoid transmitters. A purified plant-derived cannabidiol was approved in 2018 for two rare childhood epilepsies after trials showed it reduced seizures, which makes it one of the few recent examples of a plant extract becoming a licensed drug in its own right.

Used now for: Dravet and Lennox-Gastaut epilepsy, chemotherapy-induced nausea and spasticity in multiple sclerosis

In Chinese medicine: Huo Ma Ren, the seed, used as a mild laxative and free of cannabinoid activity

From

Ginkgo leaves and nuts Ginkgo biloba

When

Structures solved 1967

Who

Koji Nakanishi

Nakanishi solved the structure of the ginkgolides, cage-shaped molecules unlike anything else in plant chemistry, from a tree that has no living relatives. They block platelet-activating factor, a signal in inflammation and clotting, and that mechanism has been pursued for asthma and stroke without producing a first-line drug. Standardized leaf extract remains one of the most-sold botanicals in the world, and the evidence for it in memory is far weaker than its sales suggest.

Used now for: Sold widely as an extract; the isolated ginkgolides remain research and specialty compounds

In Chinese medicine: Bai Guo, the nut, used for wheezing and urinary frequency · read the herb page

From

Ox and pig pancreas Bos taurus, Sus scrofa

When

1921 to 1922

Who

Frederick Banting, Charles Best, James Collip and John Macleod

Type 1 diabetes was uniformly fatal, and children died within months of diagnosis. Banting and Best tied off the pancreatic ducts of dogs to let the digestive tissue waste away, then extracted what remained; Collip purified it well enough to inject. In January 1922 Leonard Thompson, fourteen and dying, received the first effective dose. The team sold the patent to the University of Toronto for one dollar. Animal insulin was the treatment for sixty years, until human sequences could be made in bacteria and yeast.

Used now for: All type 1 and much type 2 diabetes, now with recombinant and analogue insulins

From

Dog liver, then pig intestine and beef lung Sus scrofa

When

1916

Who

Jay McLean and William Howell; Charles Best again for the clinical form

McLean, a medical student, was set to purify a clotting agent from liver and found a preparation that did the opposite. The name comes from hepar, liver. Purifying it well enough to give safely took another twenty years and much of that work was done in Toronto and Stockholm. Almost all heparin is still harvested from pig intestinal mucosa, which is why a disease outbreak in pigs is a drug supply problem, and why a 2008 contamination of the Chinese supply chain killed people.

Used now for: Prevention and treatment of thrombosis, dialysis and cardiac surgery

From

Brazilian pit viper venom Bothrops jararaca

When

1965 to 1975

Who

Sergio Ferreira found the venom factor; David Cushman and Miguel Ondetti designed the drug

Workers on Brazilian plantations bitten by the jararaca collapsed with sudden low blood pressure. Ferreira showed the venom contained peptides that potentiate bradykinin, and the target turned out to be angiotensin converting enzyme. Cushman and Ondetti at Squibb built a small molecule to fit that enzyme's active site, which was one of the first drugs designed from a mechanism, not found by screening. Captopril and its successors are now among the most prescribed drugs on earth.

Used now for: Hypertension, heart failure, and protection of the kidney in diabetes

From

Gila monster venom Heloderma suspectum

When

1992

Who

John Eng, at a Bronx veterans hospital

Eng was looking for hormones in unusual places and reasoned that a lizard which eats a few enormous meals a year would need a durable version of the gut hormone that manages a meal. He bought venom with his own money and found exendin-4, a peptide close enough to human GLP-1 to activate the same receptor but resistant to the enzyme that destroys ours within minutes. His employer declined to patent it, so he patented it himself. That lizard peptide is the direct ancestor of the GLP-1 class now used for diabetes and obesity.

Used now for: Type 2 diabetes; the class it founded now includes the widely used weight-loss drugs

From

Medicinal leech saliva Hirudo medicinalis

When

Hirudin described 1884

Who

John Berry Haycraft

Leeches were used for bloodletting for two thousand years, for reasons that were wrong, and the one useful thing about them is in their saliva: hirudin, which blocks thrombin directly so the bite keeps bleeding. Haycraft described the anticoagulant effect in 1884. Recombinant and shortened synthetic versions became drugs for people who cannot receive heparin, particularly those who have developed heparin-induced low platelets. Live leeches are also still used in reconstructive surgery to drain congested tissue flaps.

Used now for: Anticoagulation during angioplasty and in heparin-induced thrombocytopenia

In Chinese medicine: Shui Zhi, the dried leech, used to break up static blood

From

Pygmy rattlesnake and saw-scaled viper venoms Sistrurus miliarius barbouri; Echis carinatus

When

Late 1980s

Who

Researchers characterising venom disintegrins

Some venoms stop the victim's blood from clotting by blocking the receptor platelets use to stick to one another. The peptides responsible were named disintegrins, and both eptifibatide and tirofiban were built to imitate the crucial fragment of one. They are given during coronary procedures precisely because they do to a patient's platelets, briefly and reversibly, what a snake does to its prey.

Used now for: Preventing clot formation during coronary angioplasty

From

Salmon thyroid tissue Oncorhynchus species

When

1960s

Who

Following Douglas Copp's discovery of the hormone in 1961

Calcitonin lowers blood calcium, and the salmon version binds the human receptor considerably more strongly than our own hormone does, which is a common and useful accident. It was widely used for Paget's disease and osteoporosis, and has since been narrowed by concerns about long-term cancer risk. It remains a case where an animal's version of a human hormone made the better drug.

Used now for: Paget's disease, hypercalcaemia of malignancy and some bone pain

From

Sheep and pig thyroid glands Ovis aries, Sus scrofa

When

1891

Who

George Redmayne Murray

Murray injected an extract of sheep thyroid into a woman with myxedema, a condition that was then a slow decline into coma, and she recovered and lived nearly thirty more years. It was among the first successful hormone replacements in medicine and it long predates any understanding of what thyroxine is. Animal-derived thyroid is still prescribed, and still argued about, alongside synthetic levothyroxine.

Used now for: Hypothyroidism, mostly with synthetic thyroxine now

From

A Caribbean sponge Cryptotethya crypta

When

Sponge nucleosides described 1951, drug approved 1969

Who

Werner Bergmann and Robert Feeney

Bergmann found nucleosides in a Florida sponge carrying an unusual sugar, which suggested that such molecules could be built with the sugar swapped out and still be taken up by cells. Cytarabine was made on that principle and became, and remains, the backbone of treatment for acute myeloid leukemia. Vidarabine from the same line of thinking was an early antiviral. This is the origin of marine pharmacology as a field.

Used now for: Acute myeloid leukemia and lymphoma involving the nervous system

From

Cone snail venom Conus magus

When

Peptide characterised in the 1980s, approved 2004

Who

Baldomero Olivera and his students

Olivera grew up in the Philippines collecting cone shells and later studied why their venom is fast enough to stop a fish mid-swim. The venoms hold hundreds of small peptides, each tuned to a specific ion channel, which makes them a catalogue of pharmacology, not a single poison. One of them blocks the calcium channel that carries pain signals in the spinal cord. As a drug it must be infused directly into spinal fluid, and it works in some people for whom morphine does not.

Used now for: Severe chronic pain unresponsive to opioids, given intrathecally

From

A mangrove sea squirt Ecteinascidia turbinata

When

Activity reported 1969, approved 2007

Who

Kenneth Rinehart isolated the compound

Extracts of a Caribbean tunicate killed cancer cells, but the animal yields so little of the active compound that harvesting it was never going to supply a drug: early production required tonnes of sea squirt for grams of material. A total synthesis, later replaced by a route starting from a bacterial fermentation product, is what made it a medicine. It is the standard example of why a promising marine compound takes decades to reach a patient.

Used now for: Advanced soft tissue sarcoma and relapsed ovarian cancer

From

A Japanese black sponge Halichondria okadai

When

Halichondrin B isolated 1986, approved 2010

Who

Isolated by Daisuke Uemura and Kiyoyuki Yamada; simplified at Eisai

Halichondrin B was extraordinarily active and available in absurdly small amounts, and its structure is one of the most complex ever taken on by synthetic chemists. Yoshito Kishi's total synthesis made research possible, and the crucial commercial insight was that only part of the huge molecule was needed. Eribulin is that simplified fragment, and it is one of the few drugs on the market whose supply depends entirely on a long chemical synthesis of a sea sponge product.

Used now for: Metastatic breast cancer and liposarcoma

From

A mineral poison, revived through a village remedy As2O3, known in Chinese medicine as Pi Shuang

When

1970s in Harbin, Western trials from 1997

Who

Zhang Tingdong and colleagues at Harbin Medical University

Arsenic was in Western pharmacopoeias for centuries and was mostly a poison. In the early 1970s a team in Harbin investigated a folk practitioner's remedy for cancer that contained arsenic, and worked out which patients it actually helped: those with acute promyelocytic leukemia, once the most lethal form. Combined with all-trans retinoic acid, arsenic trioxide turned that disease into one curable in about nine of ten cases, usually without chemotherapy. It is the strongest modern instance of a traditional preparation being narrowed into a first-line drug.

Used now for: Acute promyelocytic leukemia, with retinoic acid

In Chinese medicine: Pi Shuang, a highly toxic mineral used externally in classical practice

From

An alkali metal, first met in mineral spring water Li

When

1949

Who

John Cade, in a repurposed Melbourne hospital kitchen

Cade suspected mania was caused by a circulating toxin, injected guinea pigs with patients' urine, and used lithium salt only to dissolve uric acid for the experiment. The lithium calmed the animals, which was not the hypothesis he was testing. He gave it to ten patients with mania and the results were immediate enough to be unmistakable. It remains the most effective drug for bipolar disorder and the only one shown repeatedly to reduce suicide, and nobody can yet say clearly how it works.

Used now for: Bipolar disorder, and augmentation in treatment-resistant depression