The skinned knee is a hallmark of childhood summers. After the tears are kissed away, a time-honored ritual follows: a few squirts of a pain killing spray, a good slather of antibiotic ointment, an adhesive bandage, and then back to the neighborhood for more rites of passage.

The venerable tools of this healing ceremony may take the form of commercial consumer products but they are rooted deeply in the chemistry and pharmacy of nature.

The painkilling spray? Lidocaine, an anesthetic agent that traces its history back to cocaine from coca leaves.

The antibiotic ointment? Three different chemicals - neomycin, polymyxin B, and bacitracin - chemicals made by bacteria to fight other bacteria. Neomycin was discovered in the Nobel prize-winning laboratory of Selman Waksman.

Bacitracin has an even more colorful backstory captured in a 1945 paper from the journal, Science: it was isolated from a bacterium found in a compound fracture wound of a 7-year-old girl named Margaret Tracey (Sometimes spelled "Tracy" - the original authors were inconsistent in their own publications). Regardless of the spelling, her name is immortalized together with genus name of the Bacillus bacteria source in a multitude of "triple-antibiotic" ointments.

In fact, one would be challenged to go about life without encountering medicines derived from the natural world. Perhaps the most famous of these is aspirin, the analgesic drug derived from a chemical made in the bark of the willow tree. This humble wonder drug is still finding new uses today, especially to prevent heart attacks and even lessen their severity when taken immediately after they occur.

Pseudoephedrine for sinus congestion? Natural, from plants of the Ephedra genus.

A statin drug to lower cholesterol? Derived from a Japanese soil fungus.

Left: Photo of Pacific Yew (Taxus brevifolia), from Wikimedia Commons.

Taxol for breast cancer? From the bark of tree in the Pacific Northwest but now made in the laboratory.

Two granddaddies of natural products chemistry, David Newman and Gordon Cragg of the National Cancer Institute's Natural Product Branch, have put numbers to the propensity of nature to give us drugs. In the most recent version (2007) of their seminal roundup of 1,010 US FDA-approved drugs from 1981 through 2006, Newman and Cragg tell us that 43 drugs are marketed exactly as they occur in nature. A more prevalent situation is represented by another 232 drugs that began as natural chemicals (commonly called "natural products") but were modified in the laboratory to improve their characteristics: improved solubility, resistance to metabolism, fewer side effects, etc. Another 124 are considered biological, "a peptide or protein either isolated from an organism/cell line or produced by biotechnological means in a surrogate host." Insulin is such a drug.

The contribution of the natural world to our medicine cabinets is stunning: Natural chemicals or "semi-synthetic" chemicals modified from nature account for over 27% of our drugs.

Perhaps more noteworthy is that these numbers are not simply a historical holdover of "old" drugs. An even more recent analysis by David Swinney and Jason Anthony in the July 2011 issue of Nature Reviews Drug Discovery reveals that 18 of 50 first-in-class drugs approved between 1999 and 2008 are derived from naturally-occurring substances.

Pharmacognosy: The Study of Natural Products

Right: A historical landmark near the site around Mt. St. Helens where USDA botanist Arthur Barclay and his graduate students made the first collection of Taxus brevifolia for anticancer testing. From EMA at My Breast Cancer Journey blog.

This week, over 500 scientists who study the chemistry and pharmacology of drugs from nature are meeting in San Diego at the annual meeting of the American Society of Pharmacognosy. The society defines the field as, "the study of the physical, chemical, biochemical and biological properties of drugs, drug substances or potential drugs or drug substances of natural origin as well as the search for new drugs from natural sources." Pharmacognosy was a common topic in colleges of pharmacy until the late 1970s because the local pharmacist was the historical source of natural drug products, especially from plants. The elegant glassware containing colored water on display at some pharmacies is meant to invoke these days.

As pharmacists moved to more of a role in dispensing drugs already made elsewhere, pharmacognosy coursework became derided as, "Weeds and Seeds," and began to be supplanted with the study of all medicinal chemistry, then replaced altogether. Some colleges continued to retain their link to the past such as Purdue University with their former Department of Medicinal Chemistry and Pharmacognosy. One of the leaders there, David Nichols, is well known for his study of the chemistry of mind-altering substances - marijuana and hallucinogens from natural sources.

In fact, several of the earliest known plant medicines were psychoactive drugs used in religious ceremonies. Today, psychoactive drug research has been applied to understanding brain disorders such as schizophrenia. And following from the traditional spiritual use of these chemicals, the mushroom hallucinogen psilocybin has been used by Roland Griffith's group at Johns Hopkins to probe the basis of human spirituality.

Natural Product Drug Discovery: Not Always a Bed of Roses

Using natural products as a commercial drug source is not without its drawbacks. The anticancer drug Taxol, or paclitaxel, is an excellent illustration of the problems and promise of natural product drugs. Taxol was discovered from the bark of the Pacific yew tree and its structure elucidated by Mansukh Wani and the late Monroe Wall at Research Triangle Institute in 1971. Taxol was originally written with a little "t" when so named by Wall and Wani. When Bristol-Myers Squibb licensed the compound from NCI, they took "capital-T" Taxol as their brand name; the generic name for the drug is now paclitaxel.

Left: Our collaborator Dr. Nicholas Oberlies of the University of North Carolina at Greensboro, Department of Chemistry and Biochemistry, with his laboratory group. Together with Dr Cedric Pearce of Mycosynthetix, Inc., our research team is isolating novel anticancer drugs from filamentous fungi derived from soil and decomposing plant matter. Courtesy David Wilson/UNCG Magazine.

Because these chemicals often exist at minute levels in nature, concentrating them into a drug can result in a product that simply can't dissolve. Heroic attempts to create soluble natural products carries its own inherent problems: Taxol must be dissolved in a substance that itself can cause allergic reactions, requiring that oncologists premedicate patients with strong antihistamines and antinflammatory drugs.

Another major problem, against exemplified by Taxol, is that the supply of a drug may be limiting. When first being tested by the National Cancer Institute, the demand for the anticancer drug required that many old and slow-growing yew trees be harvested. As documented in the book, The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug by Jordan Goodman and Vivien Walsh, the need for Taxol not only endangered the tree but also threatened the Pacific Northwest habitat of the spotted owl. The scarcity of Taxol was only resolved after the chemistry group of Robert Holton at Florida State University developed a five-step scheme to synthesize the drug from another compound, 10-DAB, that came from the needles of the European yew tree, a renewable resource. Credit goes to the late French chemist, Pierre Potier, for making this critical observation and experimenting with the first semisynthesis.

Right: The marine sponge, Halichondria okadai, source of the precursor to eribulin (Halaven; Eisai), the natural product halichondrin B. Courtesy Dr Paul May, University of Bristol.

Supply issues raise other critical problems. In his new book, The Quest for the Cure, Brent Stockwell at Columbia University tells of a marine-derived compound that was the most potent hit he’d ever found against an anticancer drug target. Unfortunately, the chemical structure of the hit was not known. Moreover, the original source of the organism that produced the compound could not be located. Alas, a cancer treatment may very well still be lurking in the deep.

Challenges such as these have caused major pharmaceutical companies to scale back or eliminate their natural products drug discovery and development units. The vast majority of natural product research is now done in academia and research institutes. But drug companies will still often license, modify, and market compounds in spite of these challenges. Derek Lowe, a pharmaceutical scientist who writes the revered blog In the Pipeline, recently described the most complex commercial synthesis of a non-peptide drug to create the newly-approved drug for breast cancer, eribulin (Halaven), a derivative of a compound from a marine sponge called halichondrin B.

Why bother?

Perhaps most important is that drugs from nature have often revealed to us new mechanisms for disease treatment. Back to Taxol. Together with her scientist Paul Schiff, Susan Horwitz of Albert Einstein School of Medicine demonstrated that Taxol causes the hyperpolymerization of microtubules, cellular structures normally required for cell division. Cancer cells treated with taxol become so congested with microtubules that they couldn’t manage the ordered process of cell division. Before this compound was discovered, we had no idea that promoting microtubule polymerization was a way to kill cancer cells. The field has since developed several other similarly acting drug with a better side effect profile.

The chemical complexity of natural products is a two-edged sword. While challenging to make in the laboratory, the compounds cover more "chemical space" than man-made chemicals and are therefore often a good first step in discovering new drugs.

And even if a natural product doesn't become a drug, these chemicals can be useful tools for studying the mechanics of basic biology. The major toxin of the mushroom Amanita phalloides, α-amanitin, is a highly-selective inhibitor of RNA polymerase II, the enzyme required for manufacture of messenger RNA. The mushroom toxin is used to define processes used by this form of the polymerase as opposed to the forms that synthesize ribosomal RNA or transfer RNA. While perhaps less evident in terms of direct human benefit, natural products are used extensively in this and other areas of biological discovery.

So the next time someone tells you that science is ignorant of cures from nature, pull out a tube of Neosporin ointment. Chemicals from nature are everywhere in medicine.

And we're still searching for more.


Johnson BA, Anker H, and Meleney FL (1945) Bacitracin: A New Antibiotic Produced by a Member of the B. subtilis Group. Science 102: 376-377.

Newman DJ and Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. Journal of Natural Products 70: 461-477.

Swinney DC and Anthony J. (2011) How were new medicines discovered? Nature Reviews Drug Discovery 10: 507-519.

About the author: David Kroll is a cancer pharmacologist, science communicator, and professor working in the field of natural products drug discovery. A science blogger for over five years, he writes regularly at Terra Sigillata at the American Chemical Society's Chemical and Engineering News network, CENtral Science, Take As Directed at PLoS Blogs, and Science-Based Medicine. David can be found on Twitter @davidkroll. David holds a B.S. in Toxicology from the Philadelphia College of Pharmacy and Science and a Ph.D. in Pharmacology and Therapeutics from the University of Florida. The Kroll family resides in Durham, North Carolina.

The views expressed are those of the author and are not necessarily those of Scientific American.

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