Hunting for Cancer Killers
A quiet revolution in procedure has taken place at the National Cancer Institute. In a way, as if the manuals have been rewritten by Henry Ford, the assembly line has come to the laboratory bench.
For better than three decades, NCI has been studying compounds for possible activity against cancer. The job of its Frederick Cancer Research Facility in Bethesda, Maryland, is making the first crucial assay: does a substance kill cancerous cells? All other considerations--what side effects a tested compound might have, how it can be delivered where and as needed, what concentrations are effective--are for subsequent research.
Until recently, the chief tools in this phase of testing were legions of leukemic mice. If a test compound apparently retarded the progress of mouse leukemia, it went on to further testing. If it didn't, it was discarded. The mice have screened hundreds of thousands of compounds. From that effort, 36 licensed drugs have emerged.
As might be expected, most of the licensed drugs affect leukemia. The tests didn't find chemicals to challenge tumors of the brain, lung, or other organs. Among scientists who suspected the mouse screen was inadequate was an NCI researcher who knew the test had failed at least once. Michael Boyd had studied moldy sweet potatoes, isolating and then synthesizing a toxin that kills some lung cells. It failed the mouse test, but its activity proved to be specific to lung tumor cells. It's now in clinical trials.
Boyd feared (and complained) that other potentially useful anticancer drugs might be missed, as his extract of moldy sweet potatoes could have been. His concern was shared by others higher in NCI; in late 1983, Boyd found himself yanked from his laboratory and challenged to set up different screening procedures.
Last fall, the new system got under way. Now the test medium is a broad array of different kinds of human tumor cells, carefully selected, carefully cultured. Substances to be tested arrive from two sources. Pharmaceutical and chemical companies submit promising pure synthetic compounds, which are invented by the thousands every year. Field biologists under contract to NCI submit locally known medicinal substances, and any plants and animals having chemical defenses against predators or infectious organisms.
The testing itself does sound very like a high-tech assembly line. Each compound and extract is tested, at several dilutions, against 60 different cultured cell lines representing seven different cancer sites: blood, brain, colon, kidney, and ovary. The test cultures contain a pink dye that adheres only to living cells. A photometer automatically measures the color intensity; the more intense the pink, the less effect the tested chemical has. The measurement is recorded electronically and displayed on a computer screen.
Promising compounds, those deadly enough to cancerous cells so that the pink fades significantly, are flagged for further testing. Here mice enter the picture again, but these are implanted with human tumors. If the tested substance retards or wipes out tumorous growth in the mice, it goes on to clinical testing in people. The cell-test assembly line aims for processing 20,000 potential cancer killers every year. It's a scattershot approach, designed to look at everything that might help. Even its strongest proponents expect it might take ten years for the procedure to prove its worth--if it ever does.
Yet the gamble seems worthwhile, and not only because so many people suffer from cancer. The natural sources for promising compounds are vanishing daily. The researchers appreciate that tropical rain forests and reefs are under chronic attack, and they are justifiably afraid that something potent may be lost before they can identify it.
Having done what he can, Michael Boyd is now back in the laboratory, but as director of the branch that works at isolating the active components of substances that pass the first screen. The revolution he led is up and running.
It sounds like an expensive process, costing $4 million or so a year. But we're all potential cancer victims, and divided among the U.S. population, that $4 million looks pretty trivial. Dr. Boyd's revolution is welcome to my twenty cents.
