"Drugs to fight cancer don't just drop out of the sky," says Dr. David Newman, who directs NCI-Frederick's Natural Products Branch (NPB), "but they can come out of the ground." A good example of this is the bark of the Pacific yew tree (Taxus brevifolia), which is the source of paclitaxel (Taxol), a successful anticancer agent.
In fact, as of 2006, more than two-thirds of the 178 anticancer agents approved by the FDA and regulation agencies in other countries owe their existence to structures from the Earth's flora and fauna. And this isn't only with cancer: The cholesterol-lowering drug atorvastatin (Lipitor), for example, which is the top drug sold worldwide, is a synthetically modified version of a fungal metabolite.
NPB manages a global effort to find, collect, and process species of life that may be a source of raw material for new therapies. Either contract field collectors or collaborating organizations in the source countries provide NPB with a network to mine potential specimens in more than 25 countries. This collection is heaviest between the tropics, wher the majority of the Earth's 250,000 plant species thrive and marine invertebrates live in waters conducive to diving.
NPB is using its collection to provide researchers with promising leads for new drug development and the material with which to pursue it. NPB shares its samples with researchers from around the world who are working on any disease or medical issue of interest to the NIH.
Before researchers can receive NPB samples, however, they must sign a letter of collection, which, says Dr. Newman, "includes one fiercely nonnegotiable tenet: The source country must be involved in any subsequent drug commercialization." This stipulation came from wording in NCI's letter of collection, first signed with the Republic of Madagascar, 3 years before the Convention on Biological Diversity (CBD), an international treaty that protects global biodiversity and the rights of countries.
Since its inception in 1986, NPB's terrestrial collection has amassed more than 60,000 plant samples. Marine products form a distinct category, contributing more than 14,000 animal samples (most of them invertebrates) plus 3,000 species of algae.
A fast growing collection is microorganisms, especially fungi and bacteria developed and maintained in conjunction with the USDA at Fort Detrick, with some 30,000 of these microbes characterized. Researchers are finding an increasing number of the significant bioactive components in animal and plant species are probably produced by microbes associated with the plant or marine samples.
Chemists working with NPB process and refine all of the material into extracts and keep them in a freezer with bar codes that capture detailed information about their origin. Then they conduct initial screens using the NCI-60 cell lines and other relevant assays for biological activity against cancer.