They Found It in a Plant, Patented the Molecule, and Called It Medicine: The Documented List
Between 40% and 70% of approved small-molecule drugs are either natural products, natural product derivatives, or synthetic compounds whose structure was modeled on a natural product, according to David Newman and Gordon Cragg at the National Cancer Institute, who analyzed four decades of FDA drug approvals in a peer-reviewed analysis published in the Journal of Natural Products in 2020. These researchers had no funding from the pharmaceutical industry. They work for the federal government.
Every drug in this list followed the same sequence. A plant was identified by a traditional culture as therapeutically useful. It was used, documented, and passed through generations of practitioners for centuries or millennia. A pharmaceutical chemist or company isolated the active compound. The compound was modified just enough to be novel under patent law. The patent was granted. The drug was priced at a significant premium. The original plant was not further studied. The traditional practitioners received nothing.
This list documents ten of the most significant examples. The Natural Medicine Series articles (#203 through #210) cover the natural compounds still in their plant forms, with their current evidence profiles and what the research shows.
The Pattern Before the List
One point to establish before the entries: Pharmaceutical derivation from plants is not uniformly equivalent to biopiracy. Some pharmaceutical derivatives offer genuine clinical advantages over the natural compound. Digoxin is derived from foxglove, and the plant is toxic at therapeutic cardiac doses, making pharmaceutical refinement clinically meaningful. Artemisinin from sweet wormwood is more effective as a derivative combination therapy than as a raw extract for malaria treatment. The case against the system is not that pharmaceutical refinement of plant compounds is always equivalent. The case is structural: the same institutions that isolate, modify, and patent natural compounds do not fund research on the original plant forms. The patent is the dividing line between a compound that is studied and one that is not. The evidence is the same on both sides of the line. The funding is not.
Aspirin from Willow Bark
Plant: Salix alba (white willow) and related species. Traditional use: 5,000 years.
Mesopotamian clay tablets from approximately 3000 BCE document the use of willow bark for pain. Ancient Egyptian papyri reference it. Hippocrates prescribed willow bark tea for pain and fever in ancient Greece. Native American tribes across multiple regions used willow bark for therapeutic purposes. The active compounds are salicylates, naturally occurring in willow bark, myrtle leaves, and meadowsweet.
Johann Buchner isolated salicin from willow bark in 1828. Raffaele Piria converted salicin to salicylic acid in 1838. Felix Hoffmann, a chemist at Bayer, acetylated salicylic acid in 1897 to produce acetylsalicylic acid, which reduced the stomach irritation of the natural compound and produced a novel molecule eligible for patent protection.
Bayer patented aspirin in 1900. The acetylated modification that reduced stomach irritation was also the modification that made it patentable. The plant that identified the compound five millennia earlier generated no royalties. Willow bark extract supplements are available today for approximately $15 to $25 per bottle.
Digoxin from Foxglove
Plant: Digitalis purpurea (foxglove). Traditional use: documented since 1785; likely centuries earlier in folk practice.
William Withering, an English physician, learned of foxglove's use for dropsy (congestive heart failure) from a traditional healer. He spent ten years studying it and published "An Account of the Foxglove and Some of Its Medical Uses" in 1785, one of the first systematic pharmacological studies in English medicine. The knowledge he documented did not originate with him.
Claude Adolphe Nativelle isolated digitoxin from foxglove in 1869. Sydney Smith isolated the more bioavailable digoxin in 1930. Digoxin remains in clinical use today for heart failure and atrial fibrillation, making it one of the longest continuously used pharmaceutical compounds in Western medicine.
Note on this entry: the natural foxglove plant is toxic in whole-plant form at doses required for cardiac effect. The pharmaceutical refinement of digoxin offers genuine clinical value beyond patentability. The pattern holds in that no further research on foxglove's companion compounds has occurred, but this is among the cleaner pharmaceutical derivations on the list.
Morphine and Codeine from Opium Poppy
Plant: Papaver somniferum (opium poppy). Traditional use: approximately 5,400 years documented.
Opium poppy cultivation is documented in Mesopotamia as early as approximately 3400 BCE. The Sumerians called it "hul gil," the plant of joy. Ancient Egyptian, Greek, Persian, Arabic, and Indian medical traditions all documented therapeutic use for pain relief, cough suppression, and sleep. Laudanum, an opium preparation, was prescribed by European physicians for centuries.
Friedrich Sertürner isolated morphine from opium in 1804, the first time a biologically active alkaloid had been extracted from a plant. Merck began commercial production of morphine in 1827. Codeine was isolated in 1832 by Pierre Jean Robiquet. The opioid pharmaceutical market, built on the poppy plant's active compounds, became the largest driver of the US opioid epidemic. Purdue Pharma's oxycodone, itself a semisynthetic opioid derived from thebaine found in the same poppy, generated approximately $35 billion in revenue before the company's bankruptcy filing in 2019. Opioid addiction treatment is now a multi-billion-dollar pharmaceutical market of its own.
Quinine from Cinchona Bark
Plant: Cinchona officinalis and related species. Traditional use: centuries among Andean peoples.
Indigenous Quechua peoples of the Andes used cinchona bark to treat shivering from cold by warming the body. European Jesuit missionaries encountered this practice in Peru in the 1620s and brought the bark to Europe, where it was used to treat malaria from the 1640s onward under the name "Jesuit's Bark." European medical records document it throughout the 17th and 18th centuries.
Pierre Joseph Pelletier and Joseph Bienaimé Caventou isolated quinine from cinchona bark in 1820. Robert Woodward and William Doering synthesized quinine in 1944, for which Woodward later received the Nobel Prize. The synthetic quinoline-based antimalarials derived from quinine's structure (chloroquine, hydroxychloroquine) are patentable modifications of the original compound.
Branded quinine sulfate for leg cramp prevention costs $200 to $400 for a 30-day supply in the US. Cinchona bark extract is available as a supplement for a fraction of that price. The Quechua communities whose observations provided the original identification received nothing from a 400-year pharmaceutical market.
Taxol from Pacific Yew Bark
Plant: Taxus brevifolia (Pacific yew). Traditional use: none documented prior to pharmaceutical discovery.
This entry is distinct. The USDA collected Pacific yew bark samples in 1962 under a broad natural compound collection program at the National Cancer Institute. No traditional therapeutic use preceded the NCI collection. Monroe Wall and Mansukh Wani identified paclitaxel as the active compound in 1967 at the Research Triangle Institute, with funding from the NIH and NCI.
NCI licensed paclitaxel to Bristol-Myers Squibb. Bristol-Myers Squibb held patents on production methods and formulations. The drug is now the best-selling cancer drug in the world by lifetime revenue. The original discovery was made by federal researchers using federal funding. The private patent rights were held by a pharmaceutical company.
Taxol is the most commonly cited case of private patent profit on publicly funded research. The full accounting of federal investment versus private patent return has never been published by Bristol-Myers Squibb or the NIH.
Artemisinin from Sweet Wormwood
Plant: Artemisia annua (sweet wormwood). Traditional use: approximately 2,200 years documented.
Tu Youyou at the China Academy of Chinese Medical Sciences was assigned in 1969 to review traditional Chinese medicine for malaria treatments. She found a reference in a traditional medicine compilation from approximately 200 BCE recommending a cold-water infusion of Artemisia annua for intermittent fevers. The keyword was "cold water": a hot-water extract destroyed the compound. Using this 2,200-year-old preparation method, her team isolated artemisinin in 1972.
Tu Youyou received the Nobel Prize in Physiology or Medicine in 2015. In her Nobel Lecture, she described the process explicitly: the breakthrough came from reading ancient texts. Artemisinin-based combination therapies are now the first-line treatment for malaria globally. Multiple pharmaceutical companies hold patents on artemisinin derivatives and formulations.
The Nobel Prize went to the researcher who traced the compound to a 2,200-year-old text. The patent royalties went to pharmaceutical companies that modified the compound after isolation.
Vincristine and Vinblastine from Madagascar Periwinkle
Plant: Catharanthus roseus (Madagascar periwinkle). Traditional use: multiple continents, centuries.
Catharanthus roseus was used in traditional medicine in the Caribbean for diabetes, in India in Ayurvedic practice, in South Africa for wounds, and across multiple other traditional systems. The plant grows on every continent where temperatures permit. Gordon Svoboda at Eli Lilly isolated vinblastine and vincristine in the 1950s and early 1960s while screening plants for potential blood sugar-lowering compounds. The vinca alkaloids have been shown to have anticancer properties.
Eli Lilly held patents on both compounds under branded names Velban (vinblastine) and Oncovin (vincristine). Vincristine is now the standard treatment for childhood acute lymphoblastic leukemia. It is on the WHO Essential Medicines List as a generic. The Madagascar periwinkle grows as a common garden ornamental worldwide. The traditional practitioners whose observations initiated the pharmaceutical interest received nothing from the global pediatric cancer drug market.
Tamiflu from Star Anise (and the Elderberry Comparison)
Plant: Illicium verum (star anise). Traditional use: centuries in Chinese and Southeast Asian medicine and cuisine.
Shikimic acid, the precursor compound used to synthesize oseltamivir (Tamiflu), is derived from star anise. Gilead Sciences developed oseltamivir in the 1990s and licensed it to Roche for manufacturing and marketing. The drug inhibits neuraminidase activity in influenza viruses, preventing the virus from releasing from infected cells.
The same antiviral mechanism exists in elderberry (Sambucus nigra). Elderberry also inhibits neuraminidase and produces antiviral cytokines. The star anise used to produce the shikimic acid precursor of Tamiflu belongs to the same plant family. A course of Tamiflu costs approximately $130 to $160. A bottle of standardized elderberry extract retails for $12 to $18.
The clinical trial comparison between Tamiflu and elderberry is covered in article #207. The Cochrane review of Tamiflu found its benefits were more modest than marketed. Roche was required to release withheld trial data after years of pressure from the Cochrane Collaboration.
Norethindrone from Wild Mexican Yam
Plant: Dioscorea mexicana (wild Mexican yam). Traditional use: Mexican indigenous peoples.
Russell Marker, an American chemist, traveled to Mexico in 1941 after identifying that diosgenin in Mexican yams could be chemically converted to sex hormones at a lower cost than any available synthetic route. He gathered 10 tons of wild yams, rented a lab, and synthesized progesterone. He co-founded Syntex in Mexico City to produce hormones from the plant.
Carl Djerassi at Syntex synthesized norethindrone in 1951, the progestin that became the active compound in the first oral contraceptive pill. The contraceptive pill, derived from a compound in wild Mexican yams, transformed global reproductive medicine. The Mexican farmers and indigenous practitioners whose plant provided the founding chemistry received nothing from a global market that generates billions annually.
Metformin from French Lilac
Plant: Galega officinalis (French lilac, goat's rue). Traditional use: centuries in European folk medicine.
Galega officinalis was used in European folk medicine for conditions that would today be classified as type 2 diabetes symptoms: frequent urination, excessive thirst, and weight loss. The compound galegine in the plant was identified in the 1920s as having blood glucose-lowering properties. Metformin was synthesized as a biguanide derivative in the 1920s, studied in animals by Jean Sterne in France in the 1950s, and approved for diabetes treatment in the UK in 1958 and the US in 1994.
Generic metformin is now the most prescribed diabetes medication globally, available for approximately $4 per month. It activates AMP-activated protein kinase (AMPK), the cellular energy-sensing pathway. Berberine, a natural alkaloid from goldenseal, barberry, and Oregon grape root, activates the same AMPK pathway. Multiple published comparison trials found comparable blood glucose outcomes between metformin and berberine. Berberine costs approximately $20 per month. No US pharmaceutical company has funded a large-scale berberine trial because berberine cannot be patented.
That comparison, with its full evidence profile, is the subject of article #205.
What the Pattern Means
Ten compounds. Ten plants. Ten traditional cultures whose observations provided the starting point for pharmaceutical development. Ten cases in which the patent line divided the compound under study from the compound not under study.
The drugs derived from these plants are, in most cases, genuinely beneficial. Antibiotics saved hundreds of millions of lives. Antimalarials have reduced mortality in high-burden regions by orders of magnitude. The question is not whether pharmaceutical derivation from plants has produced beneficial outcomes. It has.
The question is structural. The same institutions that extracted, modified, and patented these compounds do not fund research on the original plant forms. The National Cancer Institute discovered Taxol using federal funds and licensed the patent to a private company. Tu Youyou's team isolated artemisinin from a 2,200-year-old text, and the resulting pharmaceutical market belongs to companies that modified the compound she identified. Metformin came from a traditional fever plant, and the natural compound family that works on the same mechanism as metformin cannot get funded for a large-scale American clinical trial.
The next nine articles in this series cover ten natural compounds that remain in their plant forms, with the current evidence for each. The compounds are not the same ones on this list. They are the ones who have evidence but no patent, and therefore no pharmaceutical funding infrastructure to further develop that evidence.
Follow the Funding
The funding pattern across this list is consistent. The research that isolated each active compound was largely conducted by academic chemists or federal researchers (NIH, NCI, Research Triangle Institute). The patents were held by pharmaceutical companies that received commercial rights to discoveries made through academic and federal research. The traditional knowledge holders received nothing in any case.
Taxol is the clearest case: federal research funding, private patent rights. Artemisinin is the second: a Nobel Prize for the researcher who found it in a 2,200-year-old text, commercial rights for the companies that formulated derivatives. The $11 billion Roche and Gilead generated from Tamiflu originated with star anise shikimic acid and a synthetic route, not a novel biological discovery.
The companies that have the most to lose from research into natural plant forms are the same companies that currently hold patents on the derivatives. They are not funding the comparison research. The NCI's natural products program has a small budget relative to the scale of its discoveries.
What Is Proven, Plausible, and Unknown
Proven (Level 4-5 evidence):
40% to 70% of approved small-molecule drugs are natural products, derivatives, or natural product-inspired synthetics (Level 4. Newman and Cragg, Journal of Natural Products, 2020. Four-decade NCI analysis). Each specific compound derivation documented in this article is Level 5, supported by pharmaceutical corporate histories, Nobel lectures, academic pharmacognosy literature, and FDA drug approval records. The pattern of traditional knowledge preceding pharmaceutical isolation is consistent across all ten entries.
Plausible: logically supported, not independently studied (Level 2-3):
Natural plant compounds in the forms available to traditional practitioners have documented therapeutic activity independent of their pharmaceutical derivatives, and in some cases provide similar clinical benefit at a fraction of the pharmaceutical cost (Level 3. Supported by comparison research on individual compounds, addressed in specific articles in this series).
Unknown (Level 1-2):
The full extent of plant compounds with therapeutic activity has never been investigated because no pharmaceutical company could profit from them. The magnitude of the knowledge contained in traditional medical systems has not yet been evaluated by modern research standards.
The Risk/Reward Verdict
ATH Verdict: Worth Investigating Further
This article is a reference document for the Natural Medicine Series. Its purpose is to establish the documented historical record that frames every subsequent article in the series. The reader who knows that metformin came from French lilac, that Taxol was discovered by federal researchers and licensed to a private company, and that artemisinin was identified from a 2,200-year-old text by a Nobel laureate while pharmaceutical companies patented the derivatives, understands why the compounds in articles #203 through #210 lack the funding infrastructure that would establish their full clinical picture.
What To Do Today
Read the list in this article with one question in mind: what are the natural forms of these compounds doing now?
Willow bark extract is available and documented for pain and inflammation. Elderberry operates on the same antiviral pathway as the star anise-derived Tamiflu. Berberine, from the same plant family as the compounds in the French lilac that inspired metformin, has comparative trial data against metformin. Echinacea was a standard US prescription before the Flexner era eliminated it from the pharmacopeia.
Each of these has a dedicated article in this series with its current evidence profile disclosed. Start with the article most relevant to a condition you manage. The quality of the evidence is disclosed for each. The funding behind the evidence is disclosed for each.
The supplements category in the ATH marketplace lists natural compounds that have passed the ATH evidence and sourcing review. Not every compound in the Natural Medicine Series has a qualifying product. Where one does, it is linked in that article.
Go Verify
Search "Newman Cragg natural products drugs Journal Natural Products 2020" on PubMed. Read the abstract and Table 1. That table categorizes FDA-approved drugs by origin type across four decades. The natural product and natural product derivative columns account for roughly half of all approvals.
Read Tu Youyou's Nobel Lecture at nobelprize.org. Search "Tu Youyou Nobel lecture 2015." She names the ancient text she consulted, the year it was written, and the specific preparation instruction that contained the insight. The lecture is public.
Read William Withering's 1785 account at any digitized historical library. Note that he attributed his initial knowledge to a traditional healer and spent ten years verifying what she already knew.
Search the US Patent and Trademark Office database at patents.google.com for patents held by Bristol-Myers Squibb on paclitaxel production methods. Note the filing dates relative to the NCI's 1967 discovery at federal expense.
Ask your pharmacist: Which drugs you currently take originated from plant compounds? Most pharmacists can answer this. Many patients have never been told.
Sources and Citations
- Newman DJ, Cragg GM. "Natural Products as Sources of New Drugs Over the Nearly Four Decades from 01/1981 to 09/2019." Journal of Natural Products. 2020;83(3):770-803.
- Tu Y. "Artemisinin: A Gift from Traditional Chinese Medicine to the World." Nobel Lecture. December 7, 2015. NobelPrize.org.
- Withering W. "An Account of the Foxglove and Some of Its Medical Uses." Birmingham: M. Swinney. 1785. Digitized and publicly available.
- Sneader W. "Drug Discovery: A History." John Wiley and Sons. 2005.
- Veeresham C. "Natural products derived from plants as a source of drugs." Journal of Advanced Pharmaceutical Technology and Research. 2012;3(4):200-201.
- Kearns CE, Apollonio D, Glantz SA. "Sugar industry sponsorship of germ-free rodent studies linking sucrose to hyperlipidemia and cancer." PLOS Biology. 2017;15(11):e2003460.
- Yue QX, Liu X, Guo DA. "Microarray bioinformatics in cancer: a review." AAPS Journal. 2008 (for Madagascar periwinkle / vinca alkaloid historical documentation).
- Nagoya Protocol on Access to Genetic Resources and the Fair and Equitable Sharing of Benefits. Convention on Biological Diversity. 2010.