Photo by D. Sillman
Fourteen years ago I wrote an essay entitled “Do We Need Nature.” In it I talked about one very important aspect of wild plants and animals: their incredible array of genes, proteins and other chemicals that might be able to be used to fight human disease. I called this the “tool box” of Nature. Recently I have come across several journal and news articles that have added to this “tool box” idea.
In “Do We Need Nature?” I used the story of the May apple (Podophyllum peltatum) (pictured above (with flower circled!)) as an example of unexpected benefits from a wild species. May apple is currently dominating the understory vegetation of many of our local forests, and its abundance and commonness belies its rich history and ethnobotanical significance.
Native Americans recognized the chemical importance of the May apple. They used dilute preparations of its rhizome to treat a wide array of maladies (from constipation to liver and kidney disease). They also used a concentrated preparation of the rhizome as a poison. European settlers learned of the properties of May apple from the native peoples and similarly utilized these oral preparations.
In 1835 the drug “podophyllin” was isolated from the May apple rhizome and by 1850 concentrated forms of podophyllin were available commercially. Podophyllin was used as a laxative, a “duct opener,” a de-worming treatment (it killed both nematodes and flatworms), and as promoter of bile synthesis and release. It also had many serious side effects and was quite toxic. A topical form of podophyllin was manufactured in 1942 and was found to be very effective in treating the genital warts caused by the human papillomavirus (HPV). HPV generated genital warts are the most common sexually transmitted disease in the world, and untreated HPV infections can lead to cervical cancers. Podophyllin, then, the secondary chemical of the abundant and unassuming May apple, plays a role in the prevention of cervical cancer!
In the April 1, 2017 issue of The Scientist, Jef Akst wrote about a scientist who helped to facilitate a large number of cancer therapy breakthroughs. Jonathan Hartwell joined the National Cancer Institute (NCI) in 1938 (and stayed there until his retirement in 1975). He set up a “natural products division” at NCI whose task was to explore natural plant chemicals for possible anti-cancer properties. Hartwell worked with fellow scientists in the Agriculture Department and at many major universities and over his 37 year career described over 3000 plant chemicals that had potential impacts on cancerous growths. Hartwell published a book (Plants Against Cancer) in 1981 in which he summarized his research. This is a very difficult book to find in a print edition, but now, fortunately, it is available in an electronic form via Google Books. Hartwell was also the author of over one hundred scientific articles and books over his long career. Summaries of Dr. Hartwell’s career can be found at http://www.altcancer.com/hartwell.htm and http://www.encognitive.com/node/4384 .
Xi Shu tree. Photo by Daderot, Wikiimedia Commons
In addition to his laboratory work, Hartwell studied the herbal and medical lore of the ancient Chinese, Egyptians, Greeks and Romans for possible clues as to which plants to analyze. Any plant that was described to have efficacy against cancer in these pre-scientific cultures was carefully evaluated by Hartwell’s lab or by one of his university affiliates.
Some notable successes from these research efforts were extracts from Chinese “happy tree” (Xi Shu tree, also known as Camptothica acuminata). Anti-cancer, chemotherapy drugs developed from this plant include camptothecin whose synthetic derivatives are still being used to treat metastatic colon and rectal cancers. Also extracts from the Pacific yew tree (Taxus brevifollia) led to isolation of the drug “taxol” which is used to treat breast, ovarian, lung, bladder, prostate and esophageal
Rosy periwinkle Photo by Ramshug Wikimedia Commons
cancers along with melanoma. Chemicals from the rosy periwinkle (Catharanthus roseus) led to the development of vinblastine which is used to treat both Hodgkin’s and non-Hodgkin’s lymphomas and vincristine which is used to treat both of these types of lymphomas and also childhood leukemia along with several other types of cancer.
The specific actions of these drugs in cells often involves disruption of the microtubules of the mitotic spindle or enzymes involved in DNA synthesis or repair. Thus, rapidly dividing cells (i.e. cancer cells) are particularly disrupted by these drugs (although even normal cells will be affected, too). As my oncologist once told me, chemotherapy is poison, but it is poison we try to control.
It has been estimated that 60% of the current cancer chemotherapy drugs are either chemicals isolated from plants or derivatives of those plant chemicals. We should all plant periwinkles (and May apples and Happy Trees!) in our gardens!
Photo by M. Dumont, Wikimedia Commons
Another part of the biological “tool box” are chemicals found in animals. A recent article in the New York Times (April 17, 2017) described a new type of antibiotic that was isolated from the blood of a Komodo dragon (Varanus komodoensis) by Monique Van Hoek and Barney Bishop of George Mason University. This antibiotic (named “DRGN-1”) killed both Gram negative and Gram positive bacteria and also dissolved their protective biofilms. It sped up wound healing in lab mice, too. The mouth of a Komodo dragon contains a rich, toxic microbiome of bacteria. When a dragon bites a large prey species (like a deer or a buffalo) it injects the bite wound with bacteria and also a recently described venom. The infection and the venom slowly disable the prey animal and the dragon, who follows the bitten prey closely, eventually can feed on the stricken animal. Researchers assumed that for a dragon to house such a toxic oral microflora, it must have mechanisms to protect itself from both self-infection and also infections from the frequent bites from their fellow, often aggressively interacting dragons. Hence the discovery of DRGN-1! Researchers report that there are forty other substances in their dragon blood that may also have antibiotic properties!
The public health fight against antibiotic resistant bacteria may depend upon the blood of dragons (and other types of monitor lizards, crocodiles and even sharks!). There are more things in heaven and earth, Horatio, than are dreamt of in our philosophies!
Happy Summer, everyone!