Organic matter for cancer drug

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Somewhere within a vast, frozen storehouse of tree bark, fungi and marine creatures, a breakthrough cancer drug may be hiding.

Cracking the code begins with crushing the samples kept in the National Cancer Institute’s repository on the grounds of Fort Detrick. Just one in 40,000 natural products yields an effective drug but scientists say the next Taxol — an anticancer agent derived from the bark of the Pacific yew tree — could be lurking in one of the repository’s 200,000 bar-coded extracts.

"Pharmaceutical companies seem to be really interested in natural products as the source of new drugs, and nature really is the architect of these beautiful new molecules,” said Gordon M. Cragg, head of the agency’s Natural Products Branch.

Cragg and David J. Newman, who heads the collection program, recently led reporters on a tour of the site. In the repository, bags of vegetable matter, marine mollusks and other organic materials from around the world are stored in 20 double-stacked, walk-in coolers well below freezing. The coolers also hold extracts made by grinding, soaking and dissolving such materials. That work is done in a nearby lab run by contractor Science Applications International Corp.

Lab manager Thomas G. McCloud said the extracts, in 120-milliter glass bottles, contain a wealth of information.

“These are not really bottles; these are library books,” he said. Reading their secrets is a laborious process. Each specimen yields two extracts — one water-based and one in an organic solvent such as oil. Each is tested against multiple kinds of cancer cells including leukemia, melanomas, and cancers of the lung, kidney, colon, central nervous system, ovaries, breast and prostate.

Any extract that shows anticancer effects is separated into compounds that are then tested against the same cells in hopes of isolating the active ingredients. Active compounds are tested in laboratory animals, and may then move on to preclinical and clinical trials conducted by the NCI or drug companies.

Each year, scientists test about 20,000 extracts, and 98 percent of them show no activity against cancer or AIDS, according to the cancer institute.

The costs of creating a marketable drug from a natural product are staggering. The General Accounting Office reports that the National Institutes of Health spent $183 million over 20 years for research on Taxol, which was approved for sale by Bristol-Myers Squibb Co. in 1992. The drug, used mainly against breast and ovarian cancers, is one of the best-selling cancer drugs in U.S. history.

Taxol is one of seven plant-derived anticancer drugs that have received Food and Drug Administration approval for commercial production since 1960, when screening of natural products began. Two of the approved drugs are derived from a tree native to China, Camptotheca acuminata. They are topotecan, manufactured by Glaxo-SmithKline under the brand name Hycamptin and used to treat lung and ovarian cancer; and irinotecan, made by Pharmacia Corp. under the brand name Camptosar for use against colorectal cancer.

Besides the search for anticancer agents, NCI began screening plants for anti-AIDS compounds in 1988. Five chemicals showing significant activity against AIDS have been isolated through that program and three are in preclinical development. They are calanolide A and calanolide B, isolated from trees found in Malaysia, and conocurovone, isolated from the saltbush shrub of western Australia. Screening of marine organisms began in 1975. That program has produced four anticancer candidates that are now in preclinical or clinical development. Their sources are a large sea slug from the Comoros Islands in the western Indian Ocean, a Caribbean sea squirt, a tiny moss animal called a bryozoan that was collected off the California coast, and a New Zealand sponge.

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